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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].
• Mesenchymal stem cell (MSC) injections represent a growing area of research in traumatology and orthopaedics [2].
• More knowledge regarding the biological properties of MSCs and endothelial progenitor cells is required before using these cells as a routinely applied therapy in the clinical setting [3].
• The intervention schedule is significantly correlated with the therapeutic efficacy of stem cells for posttraumatic osteoarthritis (PTOA) [4].
• The best effects for stem cell treatment of PTOA are observed on days 7 and 14 after anterior cruciate ligament transection (ACLT) [4].
• Exosomes offer a promising cell-free alternative to mesenchymal stem cell therapies for upper-extremity tissue regeneration [5].
• Exosomes overcome limitations such as donor-site morbidity and tumorigenesis associated with mesenchymal stem cell therapies [5].
• A better understanding of exosome mechanisms and standardized isolation methods is required before clinical application [5].
• The combination of platelet-rich plasma (PRP) and adipose-derived stem cells (ADSCs) demonstrated enhanced therapeutic efficacy for osteoarthritis [6].
• Mesenchymal stem cells have been used in clinical practice in orthopaedics and traumatology in accordance with government health regulations [7].
• The application of mesenchymal stem cells should be guided by the pathophysiology of the target disease [7].
• The application of mesenchymal stem cells should follow regulatory frameworks to ensure safe and effective use [7].
• Interventions employing PRP, MSCs, and exosomes are considered in the context of degenerative osteoarthritis as a reversible chronic disease [8].
• MSC-derived exosomes have demonstrated significant potential as a promising cell-free therapeutic strategy for osteoarthritis [9].
• Osteogenic pre-differentiation augments the therapeutic potential of adipose-derived stem cells (ASCs) for bone repair [10].
• Osteogenic pre-differentiation supports the further evaluation of ASCs in multimodal strategies for fracture nonunion [10].
• The outcome of MSC tissue engineering approaches is influenced by the methodologies and materials used during the cycle from isolation to re-implantation [11].
• The superiority of bone marrow aspirate concentrate (BMAC) over other orthobiologic treatments cannot be assessed given conflicting results presently available [12].
• BMAC-derived MSCs consistently exhibit colony-forming ability [13].
• BMAC-derived MSCs express standard MSC markers [13].
• BMAC-derived MSCs retain multipotent differentiation capacity [13].
• The viability and proliferation of BMAC-derived MSCs can be significantly affected by certain intraoperative medications [13].
• Intra-articular injection of umbilical cord–derived mesenchymal stem cells (UC-MSCs) is a viable therapeutic option for knee osteoarthritis combined with synovitis [14].
• Treatment with UC-MSCs showed clinical improvement at the end of follow-up, especially in those with moderate to severe pain [14].
• Endogenous MSCs can be pharmacologically mobilized into peripheral blood [15].
• Endogenous MSCs can be recruited to the site of rotator cuff repair via local delivery of MCP-1 [15].
• Clinical data are essential to validate results and confirm the clinical applicability of ADSC-derived exosomes in the context of tendon healing [17].
• Mesenchymal stroma cells with high osteogenic potency are contained in RIA fractions [30].
• Cells with the characteristics of stromal stem cells were isolated from irrigation fluid, which is normally discarded [30].

How It Works

Mesenchymal Stem Cells (MSCs)

• MSC injections represent a growing area of research in traumatology and orthopaedics [2].
• The application of mesenchymal stem cells should be guided by the pathophysiology of the target disease and follow regulatory frameworks to ensure safe and effective use [7].
• The outcome of MSC approaches is influenced by the methodologies and materials used during the cycle from the isolation of MSCs to their re-implantation [11].
• BMAC-derived MSCs consistently exhibit colony-forming ability, express standard MSC markers, and retain multipotent differentiation capacity [13].
• Endogenous MSCs can be pharmacologically mobilized into peripheral blood and recruited to the site of rotator cuff repair via local delivery of MCP-1 [15].
• Hypoxic MSCs might exert therapeutic effects mediated by stimulating TGF-β and subsequently promote and inhibit the expressions of COL II and COL X respectively [26].
• MiR-137 promotes TLR4/NF-κB pathway activity through targeting KDM4A, which inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells and aggravates osteoporosis [25].

Exosomes and Extracellular Vesicles

• 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 [5].
• MSC-derived exosomes have demonstrated significant potential as a promising cell-free therapeutic strategy [9].
• MSC-derived miR-125b-1-3p-abundant exosomes alleviate osteoarthritis by modulating the KDM6B-H3K27me3-FOXM1 axis [24].
• Local delivery of MSC-EVs embedded within an injectable collagen scaffold enhanced tendon regeneration in a rat model of collagenase-induced tendinopathy [18].
• Clinical data are required to validate results and confirm the clinical applicability of ADSC-derived exosomes in the context of tendon healing [17].

Combination Therapies and Carriers

• The combination of PRP and ADSCs demonstrated enhanced therapeutic efficacy for osteoarthritis [6].
• Local application of BMAC without appropriate carriers could not enhance bone-tendon interface healing [19].
• Bone marrow aspirate concentrate combined with an appropriate carrier effectively promotes bone-tendon interface healing in a rabbit model of chronic rotator cuff tear [19].

Specific Clinical Applications and Models

• 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 ACL transection [4].
• Treatment with umbilical cord-derived mesenchymal stem cells was shown to be a viable therapeutic option for knee osteoarthritis combined with synovitis, showing clinical improvement at the end of follow-up, especially in those with moderate to severe pain [14].
• The superiority of bone marrow aspirate concentrate over other orthobiologic treatments cannot be assessed given the conflicting results presently available [12].
• Osteogenic pre-differentiation augments the therapeutic potential of adipose-derived stem cells and supports their further evaluation in multimodal strategies for fracture nonunion [10].
• The application of MSCs in biodegradable scaffold in nerve injuries promotes good results in terms of regeneration and functional recovery [21].
• ASC interactions with the immune system are complex, while the secretome may be a well-tolerated treatment, though further studies are needed to determine its potential therapeutic benefits [16].

What the Evidence Shows

Clinical Efficacy and Safety

• MSCs have been used in clinical practice in orthopaedics and traumatology in accordance with government health regulations [7].
• The application of MSCs should be guided by the pathophysiology of the target disease and follow regulatory frameworks to ensure safe and effective use [7].
• Intra-articular injection of umbilical cord–derived mesenchymal stem cells (UC-MSCs) is a viable therapeutic option for knee osteoarthritis (KOA) combined with synovitis [14].
• UC-MSC treatment showed clinical improvement at the end of follow-up, especially in patients with moderate to severe pain [14].
• Arthroscopic surgical repair combined with MSC augmentation reported better structural outcomes compared to isolated surgical repair for rotator cuff tears [27].
• Augmenting hamstring allograft anterior cruciate ligament (ACL) reconstruction with an amnion collagen matrix and injecting bone marrow aspirate concentrate (BMAC) appeared to be safe [23].
• Clinical outcomes for ACL reconstruction augmented with amnion collagen matrix and BMAC injection were favorable up to 2 years postoperation [23].
• The augmentation of ACL reconstruction with amnion collagen matrix and BMAC injection had no quantifiable effect on graft maturation [23].

Mechanisms and Biological Properties

• MSCs and endothelial progenitor cells (EPCs) constitute a powerful candidate cell type for regenerative medicine [3].
• More knowledge regarding the biological properties of MSCs and EPCs is required before using these cells as a routinely applied therapy in the clinical setting [3].
• MSCs may improve osteoarthritis by secreting superoxide dismutase to regulate oxidative stress response [29].
• MSCs may act as a promising therapy in osteoarthritis through antiapoptosis and regeneration in chondrocytes by secreting superoxide dismutase and improving oxidative stress [29].

Exosomes and Cell-Free Therapies

• Exosomes overcome limitations of stem cell therapies such as donor-site morbidity and tumorigenesis [5].
• The secretome of adipose-derived mesenchymal stem cells may be a well-tolerated treatment for osteoarthritis [16].
• Further studies are needed to determine the potential therapeutic benefits of the adipose-derived mesenchymal stem cell secretome [16].
• ADSC-derived exosomes require clinical data to validate results and confirm clinical applicability in tendon healing [17].
• Local delivery of MSC-derived extracellular vesicles (EVs) embedded within an injectable collagen scaffold enhanced tendon regeneration in a rat model of collagenase-induced tendinopathy [18].
• Injection of atelocollagen containing induced pluripotent stem cell-derived tenocytes (iPSC-TCs) into the lesion after rotator cuff repair produced excellent residual effects [28].

Delivery, Timing, and Carriers

• The best effects of stem cell treatment for PTOA were observed on days 7 and 14 after anterior cruciate ligament transection [4].
• Local application of BMAC without appropriate carriers could not enhance bone-tendon interface healing in a rabbit model of chronic rotator cuff tear [19].
• BMAC combined with an appropriate carrier effectively promotes bone-tendon interface healing in a rabbit model of chronic rotator cuff tear [19].
• MSC application in biodegradable scaffold for nerve injuries promotes good results in terms of regeneration and functional recovery [21].

Research Quality and Bias

• Spin bias was present in most MSC-related trials for knee osteoarthritis [20].
• Spin bias had a higher frequency among trials that utilized adipose-derived MSCs [20].
• There is a significant risk of reporting bias in randomized controlled trials and clinical trials of MSCs for the treatment of knee osteoarthritis [22].
• Abstracts of MSC trials for knee osteoarthritis show a significantly higher proportion of significant P values compared to main texts [22].
• The superiority of BMAC over other orthobiologic treatments cannot be assessed given the conflicting results presently available [12].

Practical Considerations

• Exosomes offer a cell-free alternative to mesenchymal stem cell therapies for upper-extremity tissue regeneration [5].
• Interventions employing PRP, MSCs, and exosomes are considered for degenerative osteoarthritis [8].
• Osteogenic pre-differentiation augments the therapeutic potential of adipose-derived stem cells (ASCs) for fracture nonunion [10].
• The interaction between adipose-derived stem cells and the immune system is complex [16].
• The secretome of adipose-derived stem cells may be a well-tolerated treatment for osteoarthritis [16].
• Further studies are needed to determine the potential therapeutic benefits of the adipose-derived stem cell secretome [16].
• Augmenting hamstring allograft anterior cruciate ligament reconstruction with an amnion collagen matrix and injecting BMAC appeared to be safe [23].
• Clinical outcomes for hamstring allograft anterior cruciate ligament reconstruction augmented with an amnion collagen matrix and BMAC injection were favorable up to 2 years postoperation [23].
• Augmenting hamstring allograft anterior cruciate ligament reconstruction with an amnion collagen matrix and injecting BMAC had no quantifiable effect on graft maturation [23].
• Targeted partial arthroscopic trapeziectomy and distraction is considered suitable for a young population that does not wish to undergo invasive procedures [31].
• Targeted partial arthroscopic trapeziectomy and distraction can be used in an older population [31].

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)
• [L2] MSC injections represent a growing area of research in traumatology and orthopaedics. [2] (10.1186/s12891-025-09123-8)
• [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. [3] (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. [4] (10.1177/03635465251326499)
• [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. [5] (10.1016/j.jhsa.2023.11.016)
• [L5] The combination of PRP and ADSCs demonstrated enhanced therapeutic efficacy, suggesting its potential as a treatment option for OA. [6] (10.1186/s13018-024-05396-2)
• [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. [7] (10.1530/eor-2026-0056)
• [L5] Interventions employing PRP, MSCs and exosomes are considered in this article. [8] (10.1016/j.reth.2020.07.007)
• [L5] The findings of these studies have demonstrated the significant potential of MSC-derived exosomes as a promising cell-free therapeutic strategy. [9] (10.1186/s13018-026-06907-z)
• [Paper] These findings indicate that osteogenic pre-differentiation augments the therapeutic potential of ASCs and support their further evaluation in multimodal strategies for fracture nonunion. [10] (10.1186/s12891-026-10114-6)
• [L5] The outcome of these approaches is influenced by the methodologies and materials used during the cycle from the isolation of MSCs to their re-implantation. [11] (10.1016/s0020-1383(08)70006-8)
• [L2] However, the superiority of BMAC over other orthobiologic treatments cannot be assessed given the conflicting results presently available. [12] (10.1186/s13018-025-06509-1)
• [Paper] BMAC-derived MSCs consistently exhibit colony-forming ability, express standard MSC markers, and retain multipotent differentiation capacity, but their viability and proliferation can be significantly affected by certain intraoperative medications. [13] (10.1177/2325967126s00427)
• [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. [14] (10.1186/s12891-025-09440-y)
• [L5] Endogenous MSCs can be pharmacologically mobilized into peripheral blood and recruited to the site of rotator cuff repair via local delivery of MCP-1. [15] (10.1177/03635465251341439)
• [L5] This study highlights the complexity of ASC interactions with the immune system, while secretome may be a well-tolerated treatment, further studies are needed to determine its potential therapeutic benefits. [16] (10.1186/s12891-025-08642-8)
• [Paper] However, it is essential to obtain clinical data to validate these results and confirm the clinical applicability of ADSC-derived exosomes in the context of tendon healing. [17] (10.1016/j.jseint.2024.08.039)
• [L5] Local delivery of MSC-EVs embedded within an injectable collagen scaffold enhanced tendon regeneration in a rat model of collagenase-induced tendinopathy. [18] (10.1177/03635465261421555)
• [L5] Local application of BMAC without appropriate carriers could not enhance bone-tendon interface healing. [19] (10.1177/03635465241313124)
• [L2] Spin bias was present in most MSC-related trials for knee osteoarthritis, with a higher frequency among those that utilized adipose-derived MSCs. [20] (10.1177/03635465241274155)
• [Paper] These results suggest the MSC application in biodegradable scaffold in nerve injuries promotes good results in terms of regeneration and functional recovery. [21] (10.1016/s0020-1383(14)70003-8)
• [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. [22] (10.1177/23259671251374306)
• [L4] This case series demonstrated that augmenting hamstring allograft ACL reconstruction with an amnion collagen matrix and injecting BMAC appeared to be safe, and clinical outcomes were favorable up to 2 years postoperation despite having no quantifiable effect on graft maturation. [23] (10.1016/j.asmr.2025.101209)
• [L5] These findings provide a theoretical rationale and identify promising therapeutic targets for the development of exosome-based therapeutic strategies against OA. [24] (10.1186/s13018-026-06765-9)
• [Paper] This mechanism inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells and aggravates osteoporosis. [25] (10.1186/s13018-023-03918-y)
• [L5] Hypoxic MSCs might exert therapeutic effects mediated by stimulating TGF-β and subsequently promote and inhibit the expressions of COL II and COL X respectively. [26] (10.1186/s13018-025-06184-2)
• [L1] Arthroscopic surgical repair combined with MSC augmentation reported better structural outcomes compared to isolated surgical repair for RCT. [27] (10.1016/j.jseint.2025.03.017)
• [L5] Injection of atelocollagen containing iPSC-TCs into the lesion after rotator cuff repair produced excellent residual effects. [28] (10.1177/23259671251405287)
• [L5] The study demonstrated that MSC might be a promising therapy in OA through antiapoptosis and regeneration in chondrocyte by secreting SOD and improving oxidative stress. [29] (10.1186/s12891-025-08670-4)
• [Paper] Even in the irrigation fluid, which is normally discarded, cells with the characteristics of stromal stem cells were isolated. [30] (10.1016/s0020-1383(15)30051-6)
• [L5] The technique is considered suitable for a young population that does not wish to undergo invasive procedures, although it can be used in an older population. [31] (10.1016/j.eats.2022.08.040)

References

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

[2] 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

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

[4] 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

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

[6] 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

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

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

[9] Application of exosomes derived from mesenchymal stem cells in osteoarthritis. Journal of Orthopaedic Surgery and Research. 2026. DOI: 10.1186/s13018-026-06907-z

[10] Evaluation of mesenchymal stem cells’ bone repair capacity via osteogenic lineage differentiation in experimental nonunion fractures. BMC Musculoskeletal Disorders. 2026. DOI: 10.1186/s12891-026-10114-6

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

[12] 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

[13] Poster 123. Characterization of Human Bone Marrow Aspirate Concentrate Derived Mesenchymal Stem Cells and the Effect of Commonly Used Clinical Drugs on Their Viability and Proliferation. Orthopaedic Journal of Sports Medicine. 2026. DOI: 10.1177/2325967126s00427

[14] 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

[15] Pharmacologic Mobilization and Chemokine-Directed Recruitment of Mesenchymal Stromal Cells to the Surgically Repaired Rotator Cuff. The American Journal of Sports Medicine. 2025. DOI: 10.1177/03635465251341439

[16] Impact of adipose-derived mesenchymal stem cells and their secretome on osteoarthritis in a rat model. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08642-8

[17] Exosomes From The Adipose-Derived Stem Cells: A Novel Approach For Promoting Healing And Matrix Remodeling In Tendon Regeneration. JSES International. 2024. DOI: 10.1016/j.jseint.2024.08.039

[18] Regenerative Effect of Injectable Collagen Loaded With Mesenchymal Stem Cell–Derived Extracellular Vesicles in a Collagenase-Induced Tendinopathy Rat Model. The American Journal of Sports Medicine. 2026. DOI: 10.1177/03635465261421555

[19] Bone Marrow Aspirate Concentrate Combined With an Appropriate Carrier Effectively Promotes Bone-Tendon Interface Healing in a Rabbit Model of Chronic Rotator Cuff Tear. The American Journal of Sports Medicine. 2025. DOI: 10.1177/03635465241313124

[20] 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

[21] Peripheral nerve regeneration after experimental section in ovine radial and tibial nerves using synthetic nerve grafts, including expanded bone marrow mesenchymal cells: morphological and neurophysiological results. Injury. 2014. DOI: 10.1016/s0020-1383(14)70003-8

[22] 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

[23] Augmenting an Allograft for Anterior Cruciate Ligament Reconstruction With a Collagen Matrix and Bone Marrow Aspirate Concentrate Injection Appears Safe and Produces Favorable Clinical Outcomes at 2‐Year Follow‐Up. Arthroscopy, Sports Medicine, and Rehabilitation. 2025. DOI: 10.1016/j.asmr.2025.101209

[24] Mesenchymal stem cell-derived miR-125b-1-3p-abundant exosomes alleviate osteoarthritis by modulating the KDM6B-H3K27me3-FOXM1 axis. Journal of Orthopaedic Surgery and Research. 2026. DOI: 10.1186/s13018-026-06765-9

[25] MiR-137 promotes TLR4/NF-κB pathway activity through targeting KDM4A, inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells and aggravates osteoporosis. Journal of Orthopaedic Surgery and Research. 2023. DOI: 10.1186/s13018-023-03918-y

[26] Roles of TGF-β in the therapeutic potential of hypoxic mesenchymal stem cells for treating osteoarthritis in a Rabbit model. Journal of Orthopaedic Surgery and Research. 2025. DOI: 10.1186/s13018-025-06184-2

[27] Combined arthroscopic rotator cuff repair with mesenchymal stem cell augmentation shows similar functional outcomes but a higher structural integrity rate compared with isolated repair: a meta-analysis of comparative studies. JSES International. 2025. DOI: 10.1016/j.jseint.2025.03.017

[28] Combination of Atelocollagen Gel With Induced Pluripotent Stem Cell-Derived Tenocyte for Rotator Cuff Tendon Regeneration in a Rat Model. Orthopaedic Journal of Sports Medicine. 2026. DOI: 10.1177/23259671251405287

[29] Mesenchymal stem cells improve osteoarthritis by secreting superoxide dismutase to regulate oxidative stress response. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08670-4

[30] RIA fractions contain mesenchymal stroma cells with high osteogenic potency. Injury. 2015. DOI: 10.1016/s0020-1383(15)30051-6

[31] Targeted Partial Arthroscopic Trapeziectomy and Distraction: Surgical Technique. Arthroscopy Techniques. 2022. DOI: 10.1016/j.eats.2022.08.040