Patients › General-Health
Mga Stem Cell at Regenerative Injection
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.
Ano ito¶
Ang mga stem cell injection ay isang uri ng regenerative na gamutan. Ang ideya ay gamitin ang mga espesyal na selula mula sa sarili mong katawan, karaniwang mula sa bone marrow o taba, upang tulungan ang napinsalang tissue na pagalingin ang sarili nito. Kinukuha ang mga selulang ito, inihahanda, at pagkatapos ay ini-inject sa masakit o napinsalang bahagi, gaya ng isang pudpod na joint o isang tendon.
Sa ngayon, walang sapat na ebidensya upang irekomenda ang mga stem cell injection bilang karaniwang gamutan [1]. Inaalam pa ng mga mananaliksik sa buong mundo kung paano kumikilos ang mga selulang ito at kung talagang nakatutulong ang mga ito [2]. Walang natuklasang malinaw na benepisyo ang ilang pag-aaral para sa mga kondisyon gaya ng wear-and-tear arthritis [3]. Nagpakita naman ng maagang pangako ang iba, at mabilis na lumalago ang larangan [4]. Dahil dito, dapat lamang ialok ang mga stem cell injection bilang bahagi ng maingat na mga research trial [1].
Ganito ang pag-iisip sa likod ng gamutan. Kusang inaayos na ng iyong katawan ang sarili nito pagkatapos ng pinsala, at bahagi ng pangkat na iyon ng pag-aayos ang mga stem cell. Ang pag-asa ay mapalalakas ng pagdaragdag ng mas maraming selula sa napinsalang bahagi ang tugon ng paggaling [5]. Ipinahihiwatig ng ilang pananaliksik na maaari ring pakalmahin ng mga selulang ito ang pamamaga at maglabas ng mga kapaki-pakinabang na signal na humihikayat sa kalapit na tissue na gumaling [6]. Sinusubukan din ng mga siyentipiko ang mga paraan upang pagsamahin ang mga selula at mga sumusuportang materyales, na maaaring tumulong sa kanila na mabuhay at gumana nang mas mahusay kapag na-inject na [7].
Mas marami pa rin ang mga tanong kaysa sa mga sagot sa larangang ito [8]. Maipapaliwanag sa iyo ng iyong doktor kung ano ang ipinapakita at hindi ipinapakita ng kasalukuyang ebidensya, at kung mas angkop sa iyong sitwasyon ang isang trial o ibang napatunayang gamutan.
Gumagana ba ito?¶
Ang tapat na sagot ay nakadepende ito sa kondisyon, at sa maraming kaso ay wala pang nakaaalam. Para sa wear-and-tear arthritis ng tuhod na may pamamaga sa lining ng joint, natuklasan ng isang pag-aaral na isang magagawang opsyon ang mga injection ng mga selulang pinalaki mula sa mga donasyong umbilical cord, at bumuti ang pakiramdam ng mga tao pagsapit ng katapusan ng follow-up, lalo na ang mga nagsimula nang may katamtaman hanggang malubhang sakit [9]. Isa iyang nakapagpapalakas-loob na resulta, ngunit nagmumula ito sa isang larangan kung saan magkakahalo ang pangkalahatang larawan.
Para sa ibang gamutan sa pamilyang ito, hindi lamang nagtutugma ang mga resulta. Hindi matiyak ng mga mananaliksik na nagrepaso sa bone marrow concentrate, kung saan kinukuha ang mga selula mula sa sarili mong bone marrow at pinoproseso bago i-inject, kung mas mahusay itong gumagana kaysa sa ibang regenerative na opsyon, dahil magkakaiba ang direksyong itinuturo ng mga pag-aaral sa ngayon [10]. Natuklasan ng ilang pananaliksik na hindi sapat na matibay ang mga resulta upang irekomenda man lang ang mga stem cell para sa wear-and-tear arthritis [3].
May mga dahilan din upang basahin nang maingat ang pananaliksik na ito. Natuklasan ng mga repaso ng mga trial na sumubok sa mga selulang ito para sa arthritis ng tuhod na madalas na nakakiling sa positibo ang paraan ng pag-uulat ng mga resulta [11]. Karamihan sa mga trial na iyon ay may spin, ibig sabihin ay pinaganda ang pagkakalahad ng mga natuklasan upang magmukhang mas nakapagpapalakas-loob kaysa sa totoo [12]. Hindi ibig sabihin nito na walang silbi ang gamutan, ngunit ibig sabihin nito na dapat mong pakitunguhan nang may pag-iingat ang matatapang na pahayag.
Ito ang masasabi namin. Maaga pa, magkakahalo, at kung minsan ay nakakiling ang ebidensya. May ilang tao na nag-uulat na bumuti ang kanilang pakiramdam, at inaalam pa ng mga mananaliksik kung aling mga kondisyon, aling mga selula at aling mga pasyente ang maaaring makinabang. Maipapaliwanag sa iyo ng iyong doktor kung nasaan ang ebidensya para sa iyong partikular na problema, at kung mas angkop sa iyo ang isang research trial o isang gamutang may mas matibay na patunay.
Ano ang mga panganib?¶
Ang tapat na sagot ay inaalam pa ng mga mananaliksik kung ano ang mga panganib. Wala pang malinaw na biyolohikal na paliwanag kung paano dapat gumagana ang mga selulang ito [2], at sinasabi ng mga eksperto na kailangan ng mas maraming kaalaman bago maging karaniwang gamutan ang mga selulang ito [13]. Dahil dito, mahirap magbigay sa iyo ng maayos na listahan ng mga side effect, dahil hindi pa nagkakasundo ang larangan sa isa.
May ilang problemang lumitaw sa mismong pananaliksik. Madalas na iniulat sa nakakiling na paraan ang mga pag-aaral na sumubok sa mga selulang ito para sa arthritis ng tuhod, kung saan mas positibo ang tunog ng mga buod kaysa sa buong papel [11]. Karamihan sa mga trial na iyon ay may spin, ibig sabihin ay pinaganda ang pagkakalahad ng mga natuklasan upang magmukhang mas nakapagpapalakas-loob kaysa sa talagang totoo [12]. Panganib iyan sa iyo bilang mambabasa ng ebidensya, hindi pisikal na panganib, ngunit mahalaga ito kapag tinitimbang mo kung magpapagamot ka.
May mga tapat ding puwang sa kung ano ang kayang gawin ng mga selula. Sa isang pag-aaral, hindi sapat na matibay ang mga resulta upang irekomenda man lang ang mga stem cell para sa wear-and-tear arthritis [3]. Sa isa pa, pinunan ng repair tissue ang mga ginamot na bahagi at ang mga hindi ginamot na bahagi nang pareho, nang walang tunay na pagkakaiba sa pagitan nila [14]. Kaya isang tunay na posibilidad na dumaan ka sa mga injection at hindi bumuti ang pakiramdam mo pagkatapos.
Mukhang mahalaga rin ang paraan ng pagbibigay ng gamutan. Itinuturo ng pananaliksik na nauugnay ang timing ng mga injection sa kung gaano kahusay gumagana ang gamutan [15], at mukhang nakaaapekto rin sa resulta ang bilang ng mga selulang ginagamit [16]. Dahil wala pang napagkasunduang resipe, maaaring malaki ang nakasalalay ng iyong karanasan sa mga pagpiling inaalam pa.
Kung isinasaalang-alang mo ang mga injection na ito, itanong kung ano ang ini-inject, paano ito inihahanda, at ano ang mangyayari kung hindi ito makatulong. Maipapaliwanag sa iyo ng iyong doktor ang mga bagay na alam nating hindi pa alam para sa iyong partikular na kondisyon, at maihahambing ang mga ito sa mga panganib ng mga gamutang may mas matibay na patunay.
Tama ba ito para sa iyo?¶
Sa ngayon, hindi karaniwang gamutan ang mga stem cell injection para sa mga problema sa joint o tendon. Maaga pa at magkakahalo ang ebidensya, at walang natuklasang malinaw na benepisyo ang ilang pag-aaral para sa wear-and-tear arthritis [3]. Kaya hindi ito isang gamutan na maituturo namin at masasabing gumagana ito para sa lahat. Maaaring angkop ito sa iyo kung ang iyong kondisyon ay isa na pinag-aaralan pa ng mga mananaliksik, at kung komportable kang maging bahagi ng prosesong iyon.
Malamang na hindi ito ang tamang pagpili kung gusto mo ng gamutang may matibay at tiyak na patunay. Para sa maraming kondisyon, ang tapat na sagot ay wala pang nakaaalam kung nakatutulong ang mga injection na ito. May tunay ding tsansa na dumaan ka sa mga injection at hindi bumuti ang pakiramdam mo pagkatapos. Tinatalakay ng seksyon tungkol sa mga panganib sa itaas kung ano ang alam at hindi alam tungkol sa kaligtasan.
Kung ihahambing sa mga pangunahing alternatibo, gaya ng mga napatunayang injection, physiotherapy o operasyon, nasa ibang kategorya ang mga stem cell injection. Mas matibay ang ebidensya sa likod ng ibang mga opsyong iyon para sa maraming problema. Inaalam pa ang mga stem cell injection, kabilang ang pinakamainam na timing at ang pinakamahusay na paraan ng paghahanda ng mga selula [15].
Dapat itong maging pinagsamang desisyon mo at ng iyong doktor. Itanong kung ano ang ii-inject, paano ito ihahanda, at ano ang mangyayari kung hindi ito makatulong. Maihahambing ng iyong doktor ang opsyong ito sa mga gamutang may mas matibay na patunay, at matutulungan kang magpasya kung mas angkop sa iyong sitwasyon ang isang research trial o isang napatunayang gamutan.
Ang pinaka-importanteng punto¶
Sulit lamang pag-isipan ang mga stem cell injection kung komportable ka sa kawalang-katiyakan. Maaga pa at magkakahalo ang ebidensya, at walang natuklasang malinaw na benepisyo ang ilang pag-aaral para sa wear-and-tear arthritis [3]. Natuklasan din ng mga repaso ng mga trial sa arthritis ng tuhod na madalas iniulat ang mga resulta sa nakakiling at labis na positibong paraan [11]. Kaya pumasok nang may makatotohanang inaasahan: maaaring bumuti ang pakiramdam mo, o maaaring walang magbago. Ang pinakamahalagang paalala ay hindi pa ito isang napatunayan at karaniwang gamutan. Kung gusto mo ng tiyak na patunay sa likod ng iyong pangangalaga, maaaring mas angkop sa iyo ang isang napatunayang injection, physiotherapy o operasyon. Matutulungan ka ng iyong doktor na timbangin ito.
Mga Sanggunian¶
[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