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Tiêm tế bào gốc và các liệu pháp tái tạo

What stem-cell and bone-marrow-derived injections claim to do for joints and tendons, what the evidence actually shows, and the safety and regulatory caveats.

Updated Oct 2026
Một ống nghiệm bên cạnh một ống tiêm.
Các liệu pháp tiêm tế bào gốc và tái tạo được quảng cáo rộng rãi; bằng chứng vững chắc cho việc sử dụng trong các bệnh cơ xương khớp vẫn còn hạn chế. Kieran Hirpara 4.0

Trang này được dịch bằng máy và chưa được bác sĩ kiểm tra. Bản tiếng Anh là bản chính thức.

Định nghĩa

Tiêm tế bào gốc là một loại phương pháp điều trị tái tạo. Ý tưởng là dùng những tế bào đặc biệt lấy từ chính cơ thể bạn, thường là từ tủy xương hoặc mô mỡ, để giúp mô bị tổn thương tự lành. Các tế bào này được lấy ra, xử lý, rồi tiêm vào vùng bị đau hoặc bị tổn thương, chẳng hạn như một khớp bị hao mòn hoặc một gân.

Hiện tại, chưa có đủ bằng chứng để khuyến nghị tiêm tế bào gốc như một phương pháp điều trị thường quy [1]. Các nhà nghiên cứu trên khắp thế giới vẫn đang tìm hiểu xem các tế bào này hoạt động như thế nào và liệu chúng có thực sự giúp ích hay không [2]. Một số nghiên cứu không tìm thấy lợi ích rõ ràng đối với các bệnh như thoái hóa khớp [3]. Một số nghiên cứu khác cho thấy những kết quả ban đầu đầy hứa hẹn, và lĩnh vực này đang phát triển nhanh chóng [4]. Vì vậy, tiêm tế bào gốc chỉ nên được thực hiện trong khuôn khổ các thử nghiệm nghiên cứu được tiến hành cẩn thận [1].

Lập luận đằng sau phương pháp điều trị này như sau. Cơ thể bạn vốn đã tự sửa chữa sau chấn thương, và tế bào gốc là một phần của "đội sửa chữa" đó. Hy vọng là việc bổ sung thêm tế bào vào vùng bị tổn thương sẽ tăng cường phản ứng lành thương [5]. Một số nghiên cứu cho thấy các tế bào này cũng có thể làm dịu tình trạng viêm và tiết ra những tín hiệu có lợi giúp thúc đẩy mô xung quanh hồi phục [6]. Các nhà khoa học cũng đang thử nghiệm những cách kết hợp các tế bào với các vật liệu hỗ trợ, điều có thể giúp tế bào sống sót và hoạt động tốt hơn sau khi được tiêm vào [7].

Trong lĩnh vực này, số câu hỏi vẫn còn nhiều hơn số câu trả lời [8]. Bác sĩ có thể giải thích cho bạn những gì bằng chứng hiện nay cho thấy và chưa cho thấy, cũng như liệu một thử nghiệm nghiên cứu hay một phương pháp điều trị khác đã được chứng minh có thể phù hợp hơn với tình trạng của bạn hay không.

Phương pháp này có hiệu quả không?

Câu trả lời thẳng thắn là điều đó tùy thuộc vào từng bệnh, và trong nhiều trường hợp thì chưa ai biết. Đối với thoái hóa khớp gối có kèm sưng lớp màng lót khớp, một nghiên cứu cho thấy tiêm các tế bào được nuôi cấy từ dây rốn hiến tặng là một lựa chọn khả thi, với việc người bệnh cảm thấy dễ chịu hơn vào cuối thời gian theo dõi, đặc biệt là những người lúc đầu bị đau ở mức trung bình đến nặng [9]. Đó là một kết quả đầy hứa hẹn, nhưng nó đến từ một lĩnh vực mà bức tranh tổng thể còn chưa thống nhất.

Đối với các phương pháp điều trị khác trong cùng nhóm này, các kết quả đơn giản là không khớp với nhau. Các nhà nghiên cứu khi xem xét dịch cô đặc tủy xương, trong đó tế bào được lấy từ tủy xương của chính bạn và xử lý trước khi tiêm, không thể xác định được liệu phương pháp này có hiệu quả hơn các lựa chọn tái tạo khác hay không, vì các nghiên cứu cho đến nay chỉ ra những hướng khác nhau [10]. Một số nghiên cứu cho thấy kết quả hoàn toàn không đủ mạnh để khuyến nghị tế bào gốc cho thoái hóa khớp [3].

Cũng có những lý do để đọc các nghiên cứu này một cách thận trọng. Các bài tổng quan về những thử nghiệm dùng các tế bào này cho thoái hóa khớp gối cho thấy cách báo cáo kết quả thường thiên về hướng tích cực [11]. Phần lớn các thử nghiệm đó có hiện tượng "tô vẽ", nghĩa là các kết quả được trình bày sao cho nghe có vẻ khả quan hơn thực tế [12]. Điều đó không có nghĩa là phương pháp điều trị này vô dụng, nhưng có nghĩa là bạn nên thận trọng với những tuyên bố táo bạo.

Điều chúng tôi có thể nói là như sau. Bằng chứng còn ở giai đoạn đầu, chưa thống nhất và đôi khi bị thiên lệch. Một số người cho biết họ cảm thấy dễ chịu hơn, và các nhà nghiên cứu vẫn đang tìm hiểu xem bệnh nào, loại tế bào nào và những bệnh nhân nào có thể được hưởng lợi. Bác sĩ có thể giải thích cho bạn bằng chứng hiện nay đang ở mức nào đối với vấn đề cụ thể của bạn, và liệu một thử nghiệm nghiên cứu hay một phương pháp điều trị có bằng chứng vững chắc hơn có thể phù hợp hơn với bạn hay không.

Những rủi ro là gì?

Câu trả lời thẳng thắn là các nhà nghiên cứu vẫn đang tìm hiểu những rủi ro là gì. Hiện chưa có lời giải thích sinh học rõ ràng về cơ chế mà các tế bào này được cho là có tác dụng [2], và các chuyên gia cho rằng cần có thêm hiểu biết trước khi các tế bào này có thể trở thành một phương pháp điều trị thường quy [13]. Điều đó khiến việc đưa ra cho bạn một danh sách tác dụng phụ gọn gàng trở nên khó khăn, vì lĩnh vực này chưa thống nhất được danh sách nào.

Một số vấn đề đã xuất hiện ngay trong chính các nghiên cứu. Các nghiên cứu thử nghiệm những tế bào này cho thoái hóa khớp gối thường được báo cáo một cách thiên lệch, với phần tóm tắt nghe có vẻ tích cực hơn so với toàn văn bài báo [11]. Phần lớn các thử nghiệm đó có hiện tượng "tô vẽ", nghĩa là các kết quả được trình bày sao cho nghe có vẻ khả quan hơn thực tế [12]. Đó là một rủi ro đối với bạn với tư cách là người đọc bằng chứng, chứ không phải rủi ro về thể chất, nhưng điều này quan trọng khi bạn đang cân nhắc có nên điều trị hay không.

Cũng có những khoảng trống thực sự về những gì các tế bào này có thể làm được. Trong một nghiên cứu, kết quả hoàn toàn không đủ mạnh để khuyến nghị tế bào gốc cho thoái hóa khớp [3]. Trong một nghiên cứu khác, mô sửa chữa lấp đầy cả những vùng được điều trị lẫn những vùng không được điều trị, và không có khác biệt thực sự nào giữa chúng [14]. Vì vậy, một khả năng có thật là bạn trải qua các mũi tiêm nhưng sau đó không cảm thấy đỡ hơn.

Cách thực hiện phương pháp điều trị dường như cũng có ảnh hưởng. Nghiên cứu cho thấy thời điểm tiêm có liên quan đến hiệu quả của phương pháp điều trị [15], và số lượng tế bào được dùng dường như cũng ảnh hưởng đến kết quả [16]. Vì hiện chưa có một "công thức" được thống nhất, trải nghiệm của bạn có thể phụ thuộc nhiều vào những lựa chọn vẫn đang được nghiên cứu.

Nếu bạn đang cân nhắc những mũi tiêm này, hãy hỏi xem thứ gì sẽ được tiêm vào, được chuẩn bị như thế nào, và điều gì sẽ xảy ra nếu nó không giúp ích. Bác sĩ có thể giải thích cho bạn những điều đã biết là còn chưa rõ đối với bệnh cụ thể của bạn, và so sánh chúng với rủi ro của các phương pháp điều trị có bằng chứng vững chắc hơn.

Liệu phương pháp này có phù hợp với bạn không?

Hiện tại, tiêm tế bào gốc không phải là phương pháp điều trị thường quy cho các vấn đề về khớp hoặc gân. Bằng chứng còn ở giai đoạn đầu và chưa thống nhất, và một số nghiên cứu không tìm thấy lợi ích rõ ràng đối với thoái hóa khớp [3]. Vì vậy, đây không phải là phương pháp điều trị mà chúng tôi có thể khẳng định là hiệu quả với tất cả mọi người. Phương pháp này có thể phù hợp với bạn nếu bệnh của bạn thuộc nhóm mà các nhà nghiên cứu vẫn đang nghiên cứu, và nếu bạn cảm thấy thoải mái khi tham gia vào quá trình đó.

Đây có lẽ không phải là lựa chọn phù hợp nếu bạn muốn một phương pháp điều trị có bằng chứng mạnh mẽ và đã được khẳng định. Với nhiều bệnh, câu trả lời thẳng thắn là chưa ai biết liệu những mũi tiêm này có giúp ích hay không. Cũng có khả năng thực sự là bạn trải qua các mũi tiêm nhưng sau đó không cảm thấy đỡ hơn. Phần nói về rủi ro ở trên trình bày những gì đã biết và chưa biết về độ an toàn.

So với các lựa chọn thay thế chính, chẳng hạn như các mũi tiêm đã được chứng minh, vật lý trị liệu hoặc phẫu thuật, tiêm tế bào gốc thuộc một nhóm khác. Những lựa chọn kia có bằng chứng vững chắc hơn cho nhiều vấn đề. Tiêm tế bào gốc vẫn đang được nghiên cứu, bao gồm cả thời điểm tốt nhất và cách tốt nhất để chuẩn bị tế bào [15].

Đây nên là quyết định chung giữa bạn và bác sĩ. Hãy hỏi xem thứ gì sẽ được tiêm vào, được chuẩn bị như thế nào, và điều gì sẽ xảy ra nếu nó không giúp ích. Bác sĩ có thể so sánh lựa chọn này với các phương pháp điều trị có bằng chứng vững chắc hơn, và giúp bạn quyết định liệu một thử nghiệm nghiên cứu hay một phương pháp điều trị đã được chứng minh phù hợp hơn với tình trạng của bạn.

Tóm lại

Tiêm tế bào gốc chỉ đáng cân nhắc nếu bạn chấp nhận được sự không chắc chắn. Bằng chứng còn ở giai đoạn đầu và chưa thống nhất, và một số nghiên cứu không tìm thấy lợi ích rõ ràng đối với thoái hóa khớp [3]. Các bài tổng quan về những thử nghiệm cho thoái hóa khớp gối cũng cho thấy kết quả thường được báo cáo một cách thiên lệch, tích cực quá mức [11]. Vì vậy, hãy có kỳ vọng thực tế: bạn có thể cảm thấy đỡ hơn, hoặc có thể không thấy khác biệt gì. Lưu ý quan trọng nhất là đây chưa phải là một phương pháp điều trị thường quy đã được chứng minh. Nếu bạn muốn việc điều trị của mình dựa trên bằng chứng đã được khẳng định, một mũi tiêm đã được chứng minh, vật lý trị liệu hoặc phẫu thuật có thể phù hợp hơn với bạn. Bác sĩ có thể giúp bạn cân nhắc.

Tài liệu tham khảo

[1] Cochrane in CORR ®: Stem Cell Injections for Osteoarthritis of the Knee. Clinical Orthopaedics & Related Research. 2025. DOI: 10.1097/corr.0000000000003593

[2] 10.1002-jor.24343. n.d..

[3] Evaluation of adipose‐derived stromal vascular fraction or bone marrow‐derived mesenchymal stem cells for treatment of osteoarthritis. Journal of Orthopaedic Research. 2009. DOI: 10.1002/jor.20933

[4] Mesenchymal stem cells injections in traumatology and orthopaedics: common practice or still a promising area with many uncertainties?. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09123-8

[5] Journal of Orthopaedic Research: Special Issue on Stem Cells. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24338

[6] Prospective application of stem cells to prevent post‐operative skeletal fibrosis. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24266

[7] Biomaterial and stem cell‐based strategies for skeletal muscle regeneration. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24212

[8] Stem Cells 101: Response. The American Journal of Sports Medicine. 2021. DOI: 10.1177/03635465211042635

[9] Intra-articular injection of umbilical cord–derived mesenchymal stem cells is safe and effective for moderate to severe knee osteoarthritis with synovitis: a double‑blinded and randomized controlled trial. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09440-y

[10] Progress in the clinical use of bone marrow aspirate concentrate for knee osteoarthritis: an expert opinion. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-06509-1

[11] Analysis of P Values in the Abstract Compared With the Main Text of Randomized Controlled Trials and Clinical Trials of Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis. Orthopaedic Journal of Sports Medicine. 2025. DOI: 10.1177/23259671251374306

[12] Evaluation of Spin in Clinical Trials of Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis: A Systematic Review. The American Journal of Sports Medicine. 2025. DOI: 10.1177/03635465241274155

[13] Biological considerations of mesenchymal stem cells and endothelial progenitor cells. Injury. 2008. DOI: 10.1016/s0020-1383(08)70012-3

[14] Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model. Journal of Orthopaedic Research. 2007. DOI: 10.1002/jor.20382

[15] Days 7 to 14 May Represent an Optimal Window for Stem Cell–Based Treatment in a Rat Model of Anterior Cruciate Ligament Transection–Induced Posttraumatic Osteoarthritis. The American Journal of Sports Medicine. 2025. DOI: 10.1177/03635465251326499

[16] Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. Journal of Orthopaedic Research. 2010. DOI: 10.1002/jor.21147


Evidence & references

This is the clinical evidence summary written for health professionals. It is technical, and it lists the research this page was built from. You do not need to read it to understand your treatment or to make a decision about it.

Overview

  • There is insufficient evidence to recommend stem cell injections in clinical practice at this time [1].
  • Stem cell injections should continue to be studied in rigorous trials [1].
  • Combining stem cells and biomaterials may offer a viable therapeutic strategy that may overcome the limitations associated with these therapies when they are used in isolation [2].
  • Xenogeneic mesenchymal stem cells (MSCs) per se are not capable of regenerating in vivo [3].
  • Whether xenogeneic MSCs can be used as a vehicle to deliver target genes to host tissues remains to be tested [3].
  • Critical and clear phenotypic parameters for defining MSCs are uncertain [4].
  • A coherent biological framework surrounding the therapeutic mechanism of action is not yet available [4].
  • The success of stem cell-based therapies may benefit from cellular engineering approaches to enhance factors such as purification, homing and cell survival, trophic effects, or immunomodulatory signaling [5].
  • It is feasible to inject doses of MSCs (>0.1million) in meniscus allograft tissue with active cell proliferation, migration and robust cell survival [6].
  • Stem cells have provided tremendous promise for the development of new therapies that can treat, and possibly cure, a variety of musculoskeletal conditions [7].
  • Regenerative medicine holds great promise for orthopaedic surgery by developing novel therapies that replace, repair, or promote tissue regeneration [8].
  • MSC injections represent a growing area of research in traumatology and orthopaedics [9].
  • There are more questions than answers in the field of regenerative medicine [10].
  • A simple comparison of cell numbers between adipose-derived cultured stem cells (ASCs) and stromal vascular fraction (SVF) cells may not be meaningful because the therapeutic mode of action may be different [11].
  • The use of stem cells did not improve the results in relation to nerve regeneration at 90 days [12].
  • The findings of a study evaluating adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells were not significant enough to recommend the use of stem cells for the treatment of osteoarthritis represented in that model [13].
  • More knowledge in terms of the biological properties of MSCs and endothelial progenitor cells is required before using these cells as a routinely applied therapy in the clinical setting [14].
  • Long-term assessment revealed repair tissue filled grafted and control lesions at 8 months, with no significant difference between stem cell-treated and control defects [17].
  • The authors of a study on mesenchymal stem cell injection for osteochondral lesions of the talus requested the editor to decide whether an erratum is required to change the terminology to 'fat pad–derived cell injection' or similar [20].
  • A good relationship was found between clinical outcome and MR findings in patients treated with stem cells injection for scaphoid non-union, despite short follow-up [21].
  • The optimal differentiation conditions for transplanted MSCs needs to be further investigated to improve its clinical efficacy [22].
  • Mesenchymal stem cells (MSCs) have been used in clinical practice in orthopaedics and traumatology in accordance with government health regulations [33].
  • The application of MSCs should be guided by the pathophysiology of the target disease and follow regulatory frameworks to ensure safe and effective use [33].

How It Works

  • Xenogeneic mesenchymal stem cells (MSCs) are not capable of regenerating in vivo [3].
  • A coherent biological framework surrounding the therapeutic mechanism of action for MSCs is not yet available [4].
  • The success of stem cell-based therapies may benefit from cellular engineering approaches to enhance purification, homing, and cell survival [5].
  • Cellular engineering approaches may enhance trophic effects or immunomodulatory signaling in stem cell-based therapies [5].
  • Injecting doses of MSCs greater than 0.1 million in meniscus allograft tissue demonstrated active cell proliferation, migration, and robust cell survival [6].
  • A simple comparison of cell numbers between adipose-derived stem cells (ASCs) and stromal vascular fraction (SVF) cells may not be meaningful because the therapeutic mode of action may be different [11].
  • In a rat model of facial nerve transection, the use of stem cells did not improve results in relation to nerve regeneration at 90 days [12].
  • Findings from a study on stem cell treatment for osteoarthritis were not significant enough to recommend the use of stem cells for the treatment of osteoarthritis represented in that model [13].
  • More knowledge regarding the biological properties of MSCs and endothelial progenitor cells (EPCs) is required before using these cells as a routinely applied therapy in the clinical setting [14].
  • The intervention schedule is significantly correlated with the therapeutic efficacy of stem cells for posttraumatic osteoarthritis (PTOA) [15].
  • The best effects for stem cell treatment of PTOA were observed on days 7 and 14 after anterior cruciate ligament transection (ACLT) [15].
  • Cell-based approaches are among the principal interventions in orthobiologics to improve tendon and ligament healing and to combat degenerative processes [16].
  • Long-term assessment in an equine model revealed repair tissue filled grafted and control lesions at 8 months, with no significant difference between stem cell-treated and control defects [17].
  • Perivascular mesenchymal progenitors have resulted in efficacious bone regeneration across several preclinical models [18].
  • Clinical outcomes of administering platelet-rich plasma and mesenchymal stem cells as a combination therapy to promote bone regeneration in vivo have been highlighted [19].
  • Stem cells possess the ability to repair and regenerate damaged tissue [23].
  • Stem cells serve as a promising therapeutic approach for fibrotic diseases by inhibiting the inflammatory response and secreting favorable cytokines [23].
  • Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7 in a model of skeletal injury [24].
  • MSC transplantation effectively led to the regeneration of degenerated discs in a canine model [25].
  • The structural properties for mesenchymal stem cell-seeded Achilles tendon repairs were typically twice those for the contralateral controls as early as 4 weeks after the procedure [26].
  • Human mesenchymal stem cells (hMSCs) support a trophic effect on articular chondrocytes (ACs) [27].
  • hMSCs may have therapeutic utility even after prolonged passaging [27].
  • Intravenous injection of multipotential stem cells neither improved the degeneration status nor preserved disk height in a model of injured intervertebral disk [28].
  • Both intravenous and direct injection methods increased glycosaminoglycan (GAG) protein and Acan gene expression relative to controls, suggesting possible paracrine effects [28].
  • Intra-animal comparisons between repair tissue treated with 1-year-old MSCs and repair tissue treated with 4-year-old MSCs resulted in no significant differences in material properties including maximum stress, modulus, and strain energy density [29].
  • Repeated intra-articular injections of platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) alleviated inflammation and pain in rats with surgically induced osteoarthritis [30].
  • Repeated intra-articular injections of PRP and ADSCs promoted tissue repair and modulated immune responses in rats with surgically induced osteoarthritis [30].
  • The number of cells transplanted affects the regenerative capability of MSC transplants in experimentally induced degenerating canine discs [34].
  • Stromal cell-derived factor-1β (SDF-1b) provides potent synergistic effects supporting bone marrow-derived stem cell (BMSC)-mediated bone formation [35].
  • SDF-1b appears a suitable candidate for optimization of bone augmentation in translational protocols [35].
  • Gene editing can be used to successfully create smart stem cells capable of producing biologic drugs with antifibrotic capabilities in a controlled and localized manner [36].
  • Topical embryonic stem cells enhance wound healing in diabetic rats [37].
  • Exosomes offer a promising cell-free alternative to mesenchymal stem cell therapies for upper-extremity tissue regeneration by overcoming limitations such as donor-site morbidity and tumorigenesis [38].
  • A better understanding of exosome mechanisms and standardized isolation methods is required before clinical application [38].
  • In mice, it became possible to increase the yield of synovial mesenchymal stem cells 50-fold by inducing inflammation [39].

What the Evidence Shows

Clinical Efficacy and Safety

  • Treatment with umbilical cord–derived mesenchymal stem cells (UC-MSCs) was shown to be a viable therapeutic option for knee osteoarthritis combined with synovitis [43].
  • UC-MSC treatment showed clinical improvement at the end of follow-up, especially in those with moderate to severe pain [43].
  • The superiority of bone marrow aspirate concentrate (BMAC) over other orthobiologic treatments cannot be assessed given the conflicting results presently available [41].
  • Overall, the findings of a study evaluating adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells were not significant enough to recommend the use of stem cells for the treatment of osteoarthritis represented in that model [13].
  • At 90 days, the use of stem cells did not improve the results in relation to nerve regeneration in a rat model of facial nerve transection [12].

Preclinical and Mechanistic Findings

  • Although xenogeneic mesenchymal stem cells (MSCs) per se are not capable of regenerating in vivo, whether xenogeneic MSCs can be used as a vehicle to deliver target genes to host tissues remains to be tested [3].
  • Critical and clear phenotypic parameters for defining MSCs are uncertain and a coherent biological framework surrounding the therapeutic mechanism of action is not yet available [4].
  • A study demonstrated the feasibility of injecting doses of MSCs (>0.1million) in meniscus allograft tissue with active cell proliferation, migration and robust cell survival [6].
  • The goal of providing basic definitions for clinical colleagues regarding regenerative medicine acknowledges that there are more questions than answers in this field [10].
  • The intervention schedule is significantly correlated with the therapeutic efficacy of stem cells for posttraumatic osteoarthritis, with the best effects observed on days 7 and 14 after anterior cruciate ligament transection in a rat model [15].
  • The confluence of effects from perivascular mesenchymal progenitors has resulted in efficacious bone regeneration across several preclinical models [18].
  • A review highlights clinical outcomes of administering platelet-rich plasma and mesenchymal stem cells as a combination therapy to promote bone regeneration in vivo [19].
  • The authors of a study on osteochondral lesions of the talus requested the editor to consider changing the terminology to 'fat pad–derived cell injection' or similar [20].
  • Despite short follow-up, a good relationship was found with clinical outcome and MR findings in patients treated with stem cells injection for scaphoid non-union [21].
  • The optimal differentiation conditions for transplanted MSCs needs to be further investigated to improve its clinical efficacy in osteonecrosis of the femoral head [22].
  • Stem cells possess the ability to repair and regenerate damaged tissue and serve as a promising therapeutic approach for fibrotic diseases by inhibiting the inflammatory response and secreting favorable cytokines [23].
  • Contrasting to direct injection, intravenous injection neither improved the degeneration status nor preserved disk height, however, both delivery methods increased glycosaminoglycan (GAG) protein and Acan gene expression relative to controls, suggesting possible paracrine effects [28].
  • Intra-animal comparisons between repair tissue treated with 1-year old MSCs and repair tissue treated with 4-year old MSCs resulted in no significant differences in material properties including maximum stress, modulus, and strain energy density in rabbit tendon [29].
  • Repeated intra-articular injections of platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) alleviated inflammation and pain, promoted tissue repair, and modulated immune responses in rats with surgically induced osteoarthritis [30].
  • The use of undifferentiated MSC for cell-based transplantation therapy for articular cartilage repair is associated with more simplified laboratory processing that would not impose on additional resources and financial burden [31].
  • Interventions employing PRP, MSCs and exosomes are considered in the context of degenerative osteoarthritis as a reversible chronic disease [32].
  • The TOURNESOL consortium aims to conduct two clinical trials to repair damaged peripheral nerves (facial and limb nerves) using autologous nasal stem cell grafts [42].
  • Regenerative rehabilitation seeks to integrate regenerative medicine with rehabilitation medicine to produce better clinical outcomes than the traditional linear approach [44].
  • The results showed that the stem cell group generated significantly more new bone at the implant–allograft interface and within the graft than the control group in revision hip replacements [45].
  • A study investigated the effect of diabetes mellitus upon allograft incorporation and the augmentation of this process by mesenchymal stem cells [46].
  • A pre-clinical study demonstrates a beneficial effect of endogenous MSC mobilization on fracture healing, which may have translation potential to prevent or treat clinical fractures at risk of delayed or non-union fractures [47].
  • A review article focuses on the pathways that are followed from the isolation of MSCs, expansion and implantation [50].

Methodological and Reporting Concerns

  • A study highlights a significant risk of reporting bias in randomized controlled trials (RCTs) and clinical trials (CTs) of MSCs for the treatment of knee osteoarthritis, with abstracts showing a significantly higher proportion of significant P values compared to main texts [51].
  • Spin bias was present in most MSC-related trials for knee osteoarthritis, with a higher frequency among those that utilized adipose-derived MSCs [52].

Practical Considerations

  • It is feasible to inject doses of MSCs greater than 0.1 million in meniscus allograft tissue [6].
  • Meniscus allograft tissue receiving MSC injections demonstrates active cell proliferation, migration and robust cell survival [6].
  • A simple comparison of cell numbers between adipose-derived cultured stem cells (ASCs) and noncultured stromal vascular fraction (SVF) cells may not be meaningful because the therapeutic mode of action may be different [11].
  • The use of stem cells did not improve results in relation to nerve regeneration at 90 days [12].
  • More knowledge in terms of the biological properties of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) is required before using these cells as a routinely applied therapy in the clinical setting [14].
  • Platelet-rich plasma and mesenchymal stem cells have been administered as a combination therapy to promote bone regeneration in vivo [19].
  • The terminology for a specific cell injection study should be changed to 'fat pad–derived cell injection' or similar [20].
  • The optimal differentiation conditions for transplanted MSCs need to be further investigated to improve clinical efficacy [22].
  • Interventions employing platelet-rich plasma (PRP), mesenchymal stem cells (MSCs) and exosomes are considered in the context of degenerative osteoarthritis as a reversible chronic disease [32].
  • Bone marrow-derived stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions [40].
  • The nonadherent cell population in bone marrow culture is a complementary source of mesenchymal stem cells (MSCs) [48].
  • Collecting nonadherent cells from bone marrow culture is a simple and cost-effective way to increase MSC numbers and reduce the time required for culturing MSCs for clinical applications [48].
  • Mesenchymal stem cells (MSCs) and insulin-like growth factor-I gene-enhanced mesenchymal stem cells (AdIGF-MSCs) indicate a benefit for the treatment of tendinitis [49].

Key Evidence

  • [L1] There is insufficient evidence to recommend stem cell injections in clinical practice at this time, but they should continue to be studied in rigorous trials. [1] (10.1097/corr.0000000000003593)
  • [L5] Combining stem cells and biomaterials may offer a viable therapeutic strategy that may overcome the limitations associated with these therapies when they are used in isolation. [2] (10.1002/jor.24212)
  • [Paper] Although xenogeneic MSCs per se are not capable of regenerating in vivo, whether xenogeneic MSCs can be used as a vehicle to deliver target genes to host tissues remains to be tested. [3] (10.1002/jor.20385)
  • [Paper] The success of stem cell‐based therapies may benefit from cellular engineering approaches to enhance factors such as purification, homing and cell survival, trophic effects, or immunomodulatory signaling. [5] (10.1002/jor.24304)
  • [Paper] The study demonstrated the feasibility of injecting doses of MSCs (>0.1million) in meniscus allograft tissue with active cell proliferation, migration and robust cell survival. [6] (10.1002/jor.25074)
  • [Paper] Stem cells have provided tremendous promise for the development of new therapies that can treat, and possibly cure, a variety of musculoskeletal conditions. [7] (10.1002/jor.24338)
  • [L5] Regenerative medicine holds great promise for orthopaedic surgery by developing novel therapies that replace, repair, or promote tissue regeneration. [8] (10.1002/jor.20432)
  • [L2] MSC injections represent a growing area of research in traumatology and orthopaedics. [9] (10.1186/s12891-025-09123-8)
  • [L5] The goal was to provide basic definitions for clinical colleagues regarding regenerative medicine, acknowledging that there are more questions than answers in this field. [10] (10.1177/03635465211042635)
  • [L5] They argue that a simple comparison of cell numbers between ASCs and SVF cells may not be meaningful because the therapeutic mode of action may be different. [11] (10.1177/0363546519895242)
  • [Paper] At 90 days, it was observed that the use of stem cells did not improve the results in relation to nerve regeneration. [12] (10.1016/j.hansur.2018.10.214)
  • [Paper] Overall, the findings of this study were not significant enough to recommend the use of stem cells for the treatment of osteoarthritis represented in this model. [13] (10.1002/jor.20933)
  • [L5] Even though MSCs and EPCs constitute a powerful candidate cell type for regenerative medicine, more knowledge in terms of their biological properties is required before using these cells as a routinely applied therapy in the clinical setting. [14] (10.1016/s0020-1383(08)70012-3)
  • [L5] The intervention schedule is significantly correlated with the therapeutic efficacy of stem cells for PTOA, with the best effects observed on days 7 and 14 after ACLT. [15] (10.1177/03635465251326499)
  • [L5] Cell-based approaches are among the principal interventions in orthobiologics to improve tendon and ligament healing and to combat degenerative processes. [16] (10.1097/bte.0000000000000132)
  • [Paper] Long-term assessment revealed repair tissue filled grafted and control lesions at 8 months, with no significant difference between stem cell-treated and control defects. [17] (10.1002/jor.20382)
  • [Paper] The confluence of these effects have resulted in efficacious bone regeneration across several preclinical models. [18] (10.1002/jor.24284)
  • [L5] The paper highlights clinical outcomes of administering platelet-rich plasma and mesenchymal stem cells as a combination therapy to promote bone regeneration in vivo. [19] (10.1002/jor.24786)
  • [L5] The authors request the editor to consider their response and decide whether an erratum is required to change the terminology to 'fat pad–derived cell injection' or similar. [20] (10.1177/0363546514536691)
  • [L4] Despite the short follow-up we have found a good relationship with clinical outcome and MR findings in the patients treated with stem cells injection. [21] (10.1016/j.main.2011.10.091)
  • [Paper] The optimal differentiation conditions for transplanted MSCs needs to be further investigated to improve its clinical efficacy. [22] (10.1002/jor.20759)
  • [L5] Stem cells possess the ability to repair and regenerate damaged tissue and serve as a promising therapeutic approach for fibrotic diseases by inhibiting the inflammatory response and secreting favorable cytokines. [23] (10.1002/jor.24266)
  • [Paper] Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7. [24] (10.1002/jor.20736)
  • [Paper] MSC transplantation effectively led to the regeneration of degenerated discs. [25] (10.1002/jor.20584)
  • [L5] The structural properties for the mesenchymal stem cell-seeded repairs were typically twice those for the contralateral controls as early as 4 weeks after the procedure. [26] (10.1002/jor.1100160403)
  • [L5] This supports a trophic effect of hMSCs on ACs. hMSCs may have therapeutic utility even after prolonged passaging. [27] (10.1002/jor.22466)
  • [L3] Contrasting to direct injection, intravenous injection neither improved the degeneration status, nor preserve disk height, however, both delivery methods increased glycosaminoglycan (GAG) protein and Acan gene expression relative to controls, suggesting possible paracrine effects. [28] (10.1002/jor.22605)
  • [Paper] Intra-animal comparisons between repair tissue treated with 1-year old MSCs and repair tissue treated with 4-year old MSCs resulted in no significant differences in material properties including maximum stress, modulus, and strain energy density. [29] (10.1016/j.orthres.2004.06.017)
  • [L5] Repeated intra-articular injections of PRP and ADSCs alleviated inflammation and pain, promoted tissue repair, and modulated immune responses in rats with surgically induced OA. [30] (10.1186/s13018-024-05396-2)
  • [L3] This has a clinical implication on wider use of the undifferentiated MSC for cell-based transplantation therapy for articular cartilage repair, as this option is associated with more simplified laboratory processing that would not impose on additional resources and financial burden. [31] (10.1002/jor.21413)
  • [L5] Interventions employing PRP, MSCs and exosomes are considered in this article. [32] (10.1016/j.reth.2020.07.007)
  • [L5] Mesenchymal stem cells (MSCs) have been used in clinical practice in orthopaedics and traumatology in accordance with government health regulations, but their application should be guided by the pathophysiology of the target disease and follow regulatory frameworks to ensure safe and effective use. [33] (10.1530/eor-2026-0056)
  • [Paper] The results of this study demonstrate that the number of cells transplanted affects the regenerative capability of MSC transplants in experimentally induced degenerating canine discs. [34] (10.1002/jor.21147)
  • [Paper] SDF-1b provides potent synergistic effects supporting BMSC-mediated bone formation and appears a suitable candidate for optimization of bone augmentation in translational protocols. [35] (10.1002/jor.22749)
  • [L5] Our results show that gene editing can be used to successfully create smart stem cells capable of producing biologic drugs with antifibrotic capabilities in a controlled and localized manner. [36] (10.1002/jor.25311)
  • [Paper] The study demonstrates that topical embryonic stem cells enhance wound healing in diabetic rats. [37] (10.1002/jor.21385)
  • [L5] Exosomes offer a promising cell-free alternative to mesenchymal stem cell therapies for upper-extremity tissue regeneration by overcoming limitations such as donor-site morbidity and tumorigenesis, though a better understanding of their mechanisms and standardized isolation methods is required before clinical application. [38] (10.1016/j.jhsa.2023.11.016)
  • [Paper] In mice, it became possible to increase the yield 50-fold by inducing inflammation, which makes it possible to analyze the molecular mechanisms of cartilage regeneration of synovial mesenchymal stem cells in mouse models. [39] (10.1002/jor.22753)
  • [L5] This has important implications for tissue engineering applications of bone marrow-derived stem cells. [40] (10.1002/jor.21043)
  • [L2] However, the superiority of BMAC over other orthobiologic treatments cannot be assessed given the conflicting results presently available. [41] (10.1186/s13018-025-06509-1)
  • [Paper] The TOURNESOL consortium aims to conduct two clinical trials to repair damaged peripheral nerves (facial and limb nerves) using autologous nasal stem cell grafts. [42] (10.1016/j.hansur.2018.10.096)
  • [L1] Treatment with UC-MSCs was shown to be a viable therapeutic option for KOA combined with synovitis, showing clinical improvement at the end of follow-up, especially in those with moderate to severe pain. [43] (10.1186/s12891-025-09440-y)
  • [L5] Regenerative rehabilitation seeks to integrate regenerative medicine with rehabilitation medicine to produce better clinical outcomes than the traditional linear approach. [44] (10.1002/jor.24205)
  • [Paper] The results showed that the stem cell group generated significantly more new bone at the implant–allograft interface and within the graft than the control group. [45] (10.1002/jor.20598)
  • [Paper] The study investigated the effect of diabetes mellitus upon allograft incorporation and the augmentation of this process by mesenchymal stem cells. [46] (10.1002/jor.21065)
  • [Paper] This pre-clinical study demonstrates a beneficial effect of endogenous MSC mobilization on fracture healing, which may have translation potential to prevent or treat clinical fractures at risk of delayed or non-union fractures. [47] (10.1002/jor.24164)
  • [L4] The findings confirmed that the nonadherent cell population in the bone marrow culture is a complementary source of MSCs, and collecting these cells is a simple and cost-effective way to increase MSCs numbers and reduce the time required for culturing MSCs for clinical applications. [48] (10.1002/jor.20023)
  • [Paper] These findings indicate a benefit to the use of MSCs and AdIGF-MSCs for the treatment of tendinitis. [49] (10.1002/jor.20887)
  • [L5] This review article focuses on the pathways that are followed from the isolation of MSCs, expansion and implantation. [50] (10.1016/s0020-1383(08)70006-8)
  • [L2] The study highlights a significant risk of reporting bias in RCTs and CTs of MSCs for the treatment of knee OA, with abstracts showing a significantly higher proportion of significant P values compared to main texts. [51] (10.1177/23259671251374306)
  • [L2] Spin bias was present in most MSC-related trials for knee osteoarthritis, with a higher frequency among those that utilized adipose-derived MSCs. [52] (10.1177/03635465241274155)

References

[1] Cochrane in CORR ®: Stem Cell Injections for Osteoarthritis of the Knee. Clinical Orthopaedics & Related Research. 2025. DOI: 10.1097/corr.0000000000003593

[2] Biomaterial and stem cell‐based strategies for skeletal muscle regeneration. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24212

[3] Survival of bone marrow‐derived mesenchymal stem cells in a xenotransplantation model. Journal of Orthopaedic Research. 2007. DOI: 10.1002/jor.20385

[4] 10.1002-jor.24343. n.d..

[5] Designer Stem Cells: Genome Engineering and the Next Generation of Cell‐Based Therapies. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24304

[6] Human meniscus allograft augmentation by allogeneic mesenchymal stromal/stem cell injections. Journal of Orthopaedic Research. 2021. DOI: 10.1002/jor.25074

[7] Journal of Orthopaedic Research: Special Issue on Stem Cells. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24338

[8] Regenerative medicine in orthopaedic surgery. Journal of Orthopaedic Research. 2007. DOI: 10.1002/jor.20432

[9] Mesenchymal stem cells injections in traumatology and orthopaedics: common practice or still a promising area with many uncertainties?. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09123-8

[10] Stem Cells 101: Response. The American Journal of Sports Medicine. 2021. DOI: 10.1177/03635465211042635

[11] Comparative Clinical Outcomes After Intra-articular Injection With Adipose-Derived Cultured Stem Cells or Noncultured Stromal Vascular Fraction for the Treatment of Knee Osteoarthritis: Response. The American Journal of Sports Medicine. 2020. DOI: 10.1177/0363546519895242

[12] The use of adipose stem cells and the tubulization technique on regeneration of the facial nerve in wistar rats after transection with loss of substance. Hand Surgery and Rehabilitation. 2018. DOI: 10.1016/j.hansur.2018.10.214

[13] Evaluation of adipose‐derived stromal vascular fraction or bone marrow‐derived mesenchymal stem cells for treatment of osteoarthritis. Journal of Orthopaedic Research. 2009. DOI: 10.1002/jor.20933

[14] Biological considerations of mesenchymal stem cells and endothelial progenitor cells. Injury. 2008. DOI: 10.1016/s0020-1383(08)70012-3

[15] Days 7 to 14 May Represent an Optimal Window for Stem Cell–Based Treatment in a Rat Model of Anterior Cruciate Ligament Transection–Induced Posttraumatic Osteoarthritis. The American Journal of Sports Medicine. 2025. DOI: 10.1177/03635465251326499

[16] Cell-based Approaches for Augmentation of Tendon Repair. Techniques in Shoulder & Elbow Surgery. 2017. DOI: 10.1097/bte.0000000000000132

[17] Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model. Journal of Orthopaedic Research. 2007. DOI: 10.1002/jor.20382

[18] Perivascular Mesenchymal Progenitors for Bone Regeneration. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24284

[19] The platelet‐rich plasma and mesenchymal stem cell milieu: A review of therapeutic effects on bone healing. Journal of Orthopaedic Research. 2020. DOI: 10.1002/jor.24786

[20] Mesenchymal Stem Cell Injection for Osteochondral Lesions of the Talus: Response. The American Journal of Sports Medicine. 2014. DOI: 10.1177/0363546514536691

[21] Scaphoid non-union treatment with corticocancellous bone graft and stem cells from bone marrow. Chirurgie de la Main. 2011. DOI: 10.1016/j.main.2011.10.091

[22] Fate of mesenchymal stem cells transplanted to osteonecrosis of femoral head. Journal of Orthopaedic Research. 2009. DOI: 10.1002/jor.20759

[23] Prospective application of stem cells to prevent post‐operative skeletal fibrosis. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24266

[24] Stem cell‐mediated accelerated bone healing observed with in vivo molecular and small animal imaging technologies in a model of skeletal injury. Journal of Orthopaedic Research. 2009. DOI: 10.1002/jor.20736

[25] Transplantation of mesenchymal stem cells in a canine disc degeneration model. Journal of Orthopaedic Research. 2008. DOI: 10.1002/jor.20584

[26] Use of mesenchymal stem cells in a collagen matrix for achilles tendon repair. Journal of Orthopaedic Research. 1998. DOI: 10.1002/jor.1100160403

[27] Trophic stimulation of articular chondrocytes by late‐passage mesenchymal stem cells in coculture. Journal of Orthopaedic Research. 2013. DOI: 10.1002/jor.22466

[28] A comparison of intravenous and intradiscal delivery of multipotential stem cells on the healing of injured intervertebral disk. Journal of Orthopaedic Research. 2014. DOI: 10.1002/jor.22605

[29] Effects of age on the repair ability of mesenchymal stem cells in rabbit tendon. Journal of Orthopaedic Research. 2005. DOI: 10.1016/j.orthres.2004.06.017

[30] Adipose-derived mesenchymal stem cells combined with platelet-rich plasma are superior options for the treatment of osteoarthritis. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-024-05396-2

[31] A preliminary study comparing the use of allogenic chondrogenic pre‐differentiated and undifferentiated mesenchymal stem cells for the repair of full thickness articular cartilage defects in rabbits. Journal of Orthopaedic Research. 2011. DOI: 10.1002/jor.21413

[32] Degenerative osteoarthritis a reversible chronic disease. Regenerative Therapy. 2020. DOI: 10.1016/j.reth.2020.07.007

[33] Clinical application of mesenchymal stem cells in orthopaedics and traumatology in daily practice. EFORT Open Reviews. 2026. DOI: 10.1530/eor-2026-0056

[34] Effect of cell number on mesenchymal stem cell transplantation in a canine disc degeneration model. Journal of Orthopaedic Research. 2010. DOI: 10.1002/jor.21147

[35] Mesenchymal stem cell expression of stromal cell‐derived factor‐1β augments bone formation in a model of local regenerative therapy. Journal of Orthopaedic Research. 2014. DOI: 10.1002/jor.22749

[36] In vitro analysis of genome‐engineered muscle‐derived stem cells for autoregulated anti‐inflammatory and antifibrotic activity. Journal of Orthopaedic Research. 2022. DOI: 10.1002/jor.25311

[37] Topical embryonic stem cells enhance wound healing in diabetic rats. Journal of Orthopaedic Research. 2011. DOI: 10.1002/jor.21385

[38] The Role of Exosomes in Upper-Extremity Tissue Regeneration. The Journal of Hand Surgery. 2024. DOI: 10.1016/j.jhsa.2023.11.016

[39] Mouse synovial mesenchymal stem cells increase in yield with knee inflammation. Journal of Orthopaedic Research. 2014. DOI: 10.1002/jor.22753

[40] Bone marrow‐derived mesenchymal stem cells express the pericyte marker 3G5 in culture and show enhanced chondrogenesis in hypoxic conditions. Journal of Orthopaedic Research. 2010. DOI: 10.1002/jor.21043

[41] Progress in the clinical use of bone marrow aspirate concentrate for knee osteoarthritis: an expert opinion. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-06509-1

[42] Réparer les nerfs périphériques lésés avec des greffes autologues de cellules souches olfactives nasales. Hand Surgery and Rehabilitation. 2018. DOI: 10.1016/j.hansur.2018.10.096

[43] Intra-articular injection of umbilical cord–derived mesenchymal stem cells is safe and effective for moderate to severe knee osteoarthritis with synovitis: a double‑blinded and randomized controlled trial. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09440-y

[44] Regenerative rehabilitation: The role of mechanotransduction in orthopaedic regenerative medicine. Journal of Orthopaedic Research. 2019. DOI: 10.1002/jor.24205

[45] Use of mesenchymal stem cells to enhance bone formation around revision hip replacements. Journal of Orthopaedic Research. 2008. DOI: 10.1002/jor.20598

[46] Mesenchymal stem cells accelerate bone allograft incorporation in the presence of diabetes mellitus. Journal of Orthopaedic Research. 2010. DOI: 10.1002/jor.21065

[47] VEGF with AMD3100 endogenously mobilizes mesenchymal stem cells and improves fracture healing. Journal of Orthopaedic Research. 2018. DOI: 10.1002/jor.24164

[48] Nonadherent cell population of human marrow culture is a complementary source of mesenchymal stem cells (MSCs). Journal of Orthopaedic Research. 2005. DOI: 10.1002/jor.20023

[49] Mesenchymal stem cells and insulin‐like growth factor‐I gene‐enhanced mesenchymal stem cells improve structural aspects of healing in equine flexor digitorum superficialis tendons. Journal of Orthopaedic Research. 2009. DOI: 10.1002/jor.20887

[50] Mesenchymal stem cell tissue engineering: Techniques for isolation, expansion and application. Injury. 2007. DOI: 10.1016/s0020-1383(08)70006-8

[51] Analysis of P Values in the Abstract Compared With the Main Text of Randomized Controlled Trials and Clinical Trials of Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis. Orthopaedic Journal of Sports Medicine. 2025. DOI: 10.1177/23259671251374306

[52] Evaluation of Spin in Clinical Trials of Mesenchymal Stromal Cells for the Treatment of Knee Osteoarthritis: A Systematic Review. The American Journal of Sports Medicine. 2025. DOI: 10.1177/03635465241274155

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e. Exceptions and Limitations means fair use, fair dealing, and/or any other exception or limitation to Copyright and Similar Rights that applies to Your use of the Licensed Material.

f. Licensed Material means the artistic or literary work, database, or other material to which the Licensor applied this Public License.

g. Licensed Rights means the rights granted to You subject to the terms and conditions of this Public License, which are limited to all Copyright and Similar Rights that apply to Your use of the Licensed Material and that the Licensor has authority to license.

h. Licensor means the individual(s) or entity(ies) granting rights under this Public License.

i. NonCommercial means not primarily intended for or directed towards commercial advantage or monetary compensation. For purposes of this Public License, the exchange of the Licensed Material for other material subject to Copyright and Similar Rights by digital file-sharing or similar means is NonCommercial provided there is no payment of monetary compensation in connection with the exchange.

j. Share means to provide material to the public by any means or process that requires permission under the Licensed Rights, such as reproduction, public display, public performance, distribution, dissemination, communication, or importation, and to make material available to the public including in ways that members of the public may access the material from a place and at a time individually chosen by them.

k. Sui Generis Database Rights means rights other than copyright resulting from Directive 96/9/EC of the European Parliament and of the Council of 11 March 1996 on the legal protection of databases, as amended and/or succeeded, as well as other essentially equivalent rights anywhere in the world.

l. You means the individual or entity exercising the Licensed Rights under this Public License. Your has a corresponding meaning.

Section 2 -- Scope.

a. License grant.

1. Subject to the terms and conditions of this Public License, the Licensor hereby grants You a worldwide, royalty-free, non-sublicensable, non-exclusive, irrevocable license to exercise the Licensed Rights in the Licensed Material to:

a. reproduce and Share the Licensed Material, in whole or in part, for NonCommercial purposes only; and

b. produce, reproduce, and Share Adapted Material for NonCommercial purposes only.

2. Exceptions and Limitations. For the avoidance of doubt, where Exceptions and Limitations apply to Your use, this Public License does not apply, and You do not need to comply with its terms and conditions.

3. Term. The term of this Public License is specified in Section 6(a).

4. Media and formats; technical modifications allowed. The Licensor authorizes You to exercise the Licensed Rights in all media and formats whether now known or hereafter created, and to make technical modifications necessary to do so. The Licensor waives and/or agrees not to assert any right or authority to forbid You from making technical modifications necessary to exercise the Licensed Rights, including technical modifications necessary to circumvent Effective Technological Measures. For purposes of this Public License, simply making modifications authorized by this Section 2(a) (4) never produces Adapted Material.

5. Downstream recipients.

a. Offer from the Licensor -- Licensed Material. Every recipient of the Licensed Material automatically receives an offer from the Licensor to exercise the Licensed Rights under the terms and conditions of this Public License.

b. No downstream restrictions. You may not offer or impose any additional or different terms or conditions on, or apply any Effective Technological Measures to, the Licensed Material if doing so restricts exercise of the Licensed Rights by any recipient of the Licensed Material.

6. No endorsement. Nothing in this Public License constitutes or may be construed as permission to assert or imply that You are, or that Your use of the Licensed Material is, connected with, or sponsored, endorsed, or granted official status by, the Licensor or others designated to receive attribution as provided in Section 3(a)(1)(A)(i).

b. Other rights.

1. Moral rights, such as the right of integrity, are not licensed under this Public License, nor are publicity, privacy, and/or other similar personality rights; however, to the extent possible, the Licensor waives and/or agrees not to assert any such rights held by the Licensor to the limited extent necessary to allow You to exercise the Licensed Rights, but not otherwise.

2. Patent and trademark rights are not licensed under this Public License.

3. To the extent possible, the Licensor waives any right to collect royalties from You for the exercise of the Licensed Rights, whether directly or through a collecting society under any voluntary or waivable statutory or compulsory licensing scheme. In all other cases the Licensor expressly reserves any right to collect such royalties, including when the Licensed Material is used other than for NonCommercial purposes.

Section 3 -- License Conditions.

Your exercise of the Licensed Rights is expressly made subject to the following conditions.

a. Attribution.

1. If You Share the Licensed Material (including in modified form), You must:

a. retain the following if it is supplied by the Licensor with the Licensed Material:

i. identification of the creator(s) of the Licensed Material and any others designated to receive attribution, in any reasonable manner requested by the Licensor (including by pseudonym if designated);

ii. a copyright notice;

iii. a notice that refers to this Public License;

iv. a notice that refers to the disclaimer of warranties;

v. a URI or hyperlink to the Licensed Material to the extent reasonably practicable;

b. indicate if You modified the Licensed Material and retain an indication of any previous modifications; and

c. indicate the Licensed Material is licensed under this Public License, and include the text of, or the URI or hyperlink to, this Public License.

2. You may satisfy the conditions in Section 3(a)(1) in any reasonable manner based on the medium, means, and context in which You Share the Licensed Material. For example, it may be reasonable to satisfy the conditions by providing a URI or hyperlink to a resource that includes the required information.

3. If requested by the Licensor, You must remove any of the information required by Section 3(a)(1)(A) to the extent reasonably practicable.

4. If You Share Adapted Material You produce, the Adapter's License You apply must not prevent recipients of the Adapted Material from complying with this Public License.

Section 4 -- Sui Generis Database Rights.

Where the Licensed Rights include Sui Generis Database Rights that apply to Your use of the Licensed Material:

a. for the avoidance of doubt, Section 2(a)(1) grants You the right to extract, reuse, reproduce, and Share all or a substantial portion of the contents of the database for NonCommercial purposes only;

b. if You include all or a substantial portion of the database contents in a database in which You have Sui Generis Database Rights, then the database in which You have Sui Generis Database Rights (but not its individual contents) is Adapted Material; and

c. You must comply with the conditions in Section 3(a) if You Share all or a substantial portion of the contents of the database.

For the avoidance of doubt, this Section 4 supplements and does not replace Your obligations under this Public License where the Licensed Rights include other Copyright and Similar Rights.

Section 5 -- Disclaimer of Warranties and Limitation of Liability.

a. UNLESS OTHERWISE SEPARATELY UNDERTAKEN BY THE LICENSOR, TO THE EXTENT POSSIBLE, THE LICENSOR OFFERS THE LICENSED MATERIAL AS-IS AND AS-AVAILABLE, AND MAKES NO REPRESENTATIONS OR WARRANTIES OF ANY KIND CONCERNING THE LICENSED MATERIAL, WHETHER EXPRESS, IMPLIED, STATUTORY, OR OTHER. THIS INCLUDES, WITHOUT LIMITATION, WARRANTIES OF TITLE, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, NON-INFRINGEMENT, ABSENCE OF LATENT OR OTHER DEFECTS, ACCURACY, OR THE PRESENCE OR ABSENCE OF ERRORS, WHETHER OR NOT KNOWN OR DISCOVERABLE. WHERE DISCLAIMERS OF WARRANTIES ARE NOT ALLOWED IN FULL OR IN PART, THIS DISCLAIMER MAY NOT APPLY TO YOU.

b. TO THE EXTENT POSSIBLE, IN NO EVENT WILL THE LICENSOR BE LIABLE TO YOU ON ANY LEGAL THEORY (INCLUDING, WITHOUT LIMITATION, NEGLIGENCE) OR OTHERWISE FOR ANY DIRECT, SPECIAL, INDIRECT, INCIDENTAL, CONSEQUENTIAL, PUNITIVE, EXEMPLARY, OR OTHER LOSSES, COSTS, EXPENSES, OR DAMAGES ARISING OUT OF THIS PUBLIC LICENSE OR USE OF THE LICENSED MATERIAL, EVEN IF THE LICENSOR HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH LOSSES, COSTS, EXPENSES, OR DAMAGES. WHERE A LIMITATION OF LIABILITY IS NOT ALLOWED IN FULL OR IN PART, THIS LIMITATION MAY NOT APPLY TO YOU.

c. The disclaimer of warranties and limitation of liability provided above shall be interpreted in a manner that, to the extent possible, most closely approximates an absolute disclaimer and waiver of all liability.

Section 6 -- Term and Termination.

a. This Public License applies for the term of the Copyright and Similar Rights licensed here. However, if You fail to comply with this Public License, then Your rights under this Public License terminate automatically.

b. Where Your right to use the Licensed Material has terminated under Section 6(a), it reinstates:

1. automatically as of the date the violation is cured, provided it is cured within 30 days of Your discovery of the violation; or

2. upon express reinstatement by the Licensor.

For the avoidance of doubt, this Section 6(b) does not affect any right the Licensor may have to seek remedies for Your violations of this Public License.

c. For the avoidance of doubt, the Licensor may also offer the Licensed Material under separate terms or conditions or stop distributing the Licensed Material at any time; however, doing so will not terminate this Public License.

d. Sections 1, 5, 6, 7, and 8 survive termination of this Public License.

Section 7 -- Other Terms and Conditions.

a. The Licensor shall not be bound by any additional or different terms or conditions communicated by You unless expressly agreed.

b. Any arrangements, understandings, or agreements regarding the Licensed Material not stated herein are separate from and independent of the terms and conditions of this Public License.

Section 8 -- Interpretation.

a. For the avoidance of doubt, this Public License does not, and shall not be interpreted to, reduce, limit, restrict, or impose conditions on any use of the Licensed Material that could lawfully be made without permission under this Public License.

b. To the extent possible, if any provision of this Public License is deemed unenforceable, it shall be automatically reformed to the minimum extent necessary to make it enforceable. If the provision cannot be reformed, it shall be severed from this Public License without affecting the enforceability of the remaining terms and conditions.

c. No term or condition of this Public License will be waived and no failure to comply consented to unless expressly agreed to by the Licensor.

d. Nothing in this Public License constitutes or may be interpreted as a limitation upon, or waiver of, any privileges and immunities that apply to the Licensor or You, including from the legal processes of any jurisdiction or authority.


Creative Commons is not a party to its public licenses. Notwithstanding, Creative Commons may elect to apply one of its public licenses to material it publishes and in those instances will be considered the “Licensor.” The text of the Creative Commons public licenses is dedicated to the public domain under the CC0 Public Domain Dedication. Except for the limited purpose of indicating that material is shared under a Creative Commons public license or as otherwise permitted by the Creative Commons policies published at creativecommons.org/policies, Creative Commons does not authorize the use of the trademark "Creative Commons" or any other trademark or logo of Creative Commons without its prior written consent including, without limitation, in connection with any unauthorized modifications to any of its public licenses or any other arrangements, understandings, or agreements concerning use of licensed material. For the avoidance of doubt, this paragraph does not form part of the public licenses.

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