Management of platelet-rich plasma and stem cells versus conventional treatments in musculoskeletal injury repair: A systematic review

INTRODUCTION

Musculoskeletal injuries constitute a leading cause of morbidity and functional impairment, exerting a substantial burden on quality of life. Conventional therapeutic approaches – such as physical rehabilitation, non-steroidal anti-inflammatory drugs (NSAIDs), and surgical procedures in severe cases – are widely used but often provide limited and inconsistent outcomes in terms of pain relief, recovery speed, and recurrence rates.^[1]

In response to these limitations, biologically based interventions have garnered increasing attention. Platelet-rich plasma (PRP), derived from autologous blood and enriched with growth factors, has demonstrated potential to accelerate tissue healing. Likewise, stem cell (SC) therapy, particularly using mesenchymal stem cells (MSCs), is of interest due to its capacity for differentiating and regenerating damaged musculoskeletal structures.^[2]

These therapies have been prioritized in this review because conventional treatments often fail to promote tissue regeneration and tend to offer only symptomatic relief. In contrast, PRP and SCs hold biological potential to target the underlying pathophysiology of musculoskeletal damage.

Despite the expanding body of research on these therapies, findings remain inconclusive. Some clinical studies report significant improvements in pain, function, and tissue repair with PRP or SC, while others show marginal or no added benefit over traditional treatments. Further complicating interpretation, the protocols for preparing and applying these therapies vary widely, limiting comparability and clinical translation.^[3]

Recent studies, including those by Shanmugasundaram et al. (2021)^[4] and Tsubosaka et al. (2021),^[5] highlight the promise of these biologics but emphasize the need for standardized methods and rigorous clinical trials.

Given the regenerative capabilities of PRP and SC, it is hypothesized that these modalities may provide superior clinical outcomes compared to conventional treatments in musculoskeletal injury management. This systematic review addresses the question: How do PRP and SC therapies compare with conventional interventions in terms of efficacy, safety, and functional recovery in musculoskeletal injuries?^[6]

To answer this, a structured literature review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on randomized controlled trials (RCTs) that evaluated PRP and/or SC therapies in comparison to standard treatments. Primary outcomes included pain reduction, functional recovery, and time to return to activity. Secondary outcomes examined adverse events and quality-of-life indicators.^[7,8]

This review is expected to provide a clear and evidence-based synthesis of the usefulness of PRP and stem cells in managing musculoskeletal injuries, which could contribute to optimizing therapeutic strategies and supporting clinical decision-making.

MATERIALS AND METHODS

Search methods for study identification

Electronic searches

Systematic searches were performed in the following electronic databases:

MEDLINE (via PubMed), Embase, LILACS

These databases were selected due to their comprehensive coverage of biomedical literature, including clinical trials and Latin American publications relevant to musculoskeletal conditions. The study selection process is illustrated in Figure 1.

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Figure 1:

PRISMA 2020 flow diagram illustrating the process of study selection. A total of 437 records were identified, of which 122 were screened after removing duplicates and ineligible records. Ultimately, 23 studies met the inclusion criteria and were included in the systematic review.

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Language restrictions were applied to include only studies published in English and Spanish, as these languages were accessible to the research team. Studies in other languages were excluded due to limitations in translation capacity.

Search strategy

(“Platelet-Rich Plasma” [MeSH Terms] OR “platelet-rich plasma” [Title/Abstract] OR PRP [Title/Abstract]) AND (“Stem Cells” [MeSH Terms] OR “stem cells” [Title/Abstract] OR “mesenchymal stem cells” [Title/Abstract] OR MSCs [Title/Abstract]) AND (“Musculoskeletal Diseases” [MeSH Terms] OR “musculoskeletal injuries” [Title/Abstract] OR “musculoskeletal lesions” [Title/Abstract] OR “muscle injuries” [Title/Abstract] OR “tendon injuries” [Title/Abstract] OR “ligament injuries” [Title/Abstract] OR “bone injuries” [Title/Abstract]) AND (“Pain” [MeSH Terms] OR pain [Title/Abstract] OR “pain reduction” [Title/Abstract]) AND (“Treatment Outcome” [MeSH Terms] OR “treatment outcome” [Title/Abstract] OR “functional improvement” [Title/Abstract] OR “recovery time” [Title/Abstract] OR “time to recovery” [Title/Abstract]).

Additional boolean strategy

([tw: (“Platelet-Rich Plasma” OR “PRP” OR “platelet-rich fibrin” OR “autologous platelet concentrate” OR “platelet-derived growth factors” OR “platelet concentrate” OR “platelet gel” OR “platelet lysate”)] OR [mh: “Plasma Rico en Plaquetas”]) AND ([tw: (“Stem Cells” OR “mesenchymal stem cells” OR MSC OR “progenitor cells” OR “bone marrow-derived cells” OR “adipose-derived stem cells” OR “hematopoietic stem cells” OR “stromal cells” OR “pluripotent stem cells” OR “multipotent stem cells” OR “induced pluripotent stem cells” OR “iPSC”)] OR [mh: “Células Madre”]) AND ([tw: (“musculoskeletal injuries” OR “musculoskeletal disorders” OR “musculoskeletal trauma” OR “muscle injuries” OR “muscle tears” OR “tendon injuries” OR “tendon tears” OR “ligament injuries” OR “ligament tears” OR “cartilage injuries” OR “cartilage degeneration” OR “bone fractures” OR “joint injuries” OR “osteoarthritis” OR “sports injuries” OR “soft tissue injuries” OR “connective tissue injuries” OR “degenerative joint diseases”)] OR [mh: “Lesiones Musculoesqueléticas”] OR [mh: “Enfermedades Musculoesqueléticas”]) AND ([tw: (“pain relief ” OR “pain reduction” OR “pain management” OR “analgesia” OR “functional recovery” OR “rehabilitation” OR “functional improvement” OR “healing time” OR “recovery time” OR “wound healing” OR “tissue repair” OR “regeneration” OR “mobility improvement”)] OR [mh: “Dolor”] OR [mh: ‘Recuperación Funcional”] OR [mh: “Cicatrización”]).

Search for other resources

The references of the included articles were reviewed to identify additional studies.

RESULTS

The studies included in this systematic review evaluated the effectiveness, efficacy, and safety of PRP and SCs therapies compared to conventional treatments for the repair of musculoskeletal injuries. An overview of the main findings is summarized.

In patients with knee OA, the administration of mesenchymal stem cells (MSCs) with or without PRP showed significant improvements in both the global Knee Injury and Osteoarthritis Outcome Score (KOOS) and pain scores at 12 months compared to corticosteroids, with statistically significant differences in pain reduction (Δ23.2, P < 0.001) and functional improvement (Δ24.0, P = 0.002).^[9] Similarly, Prizov et al. reported that PRP significantly improved global KOOS scores (Δ + 40 points, P < 0.05) and reduced VAS pain scores (Δ–5 points, P < 0.05) in patients undergoing high tibial osteotomy, with better cartilage regeneration observed in those treated with stromal vascular fraction (SVF).^[10] In patients with lumbar disc degenerative disease, SVF injection with PRP resulted in a 35.7% reduction in VAS pain scores (P = 0.01) and a 19.1% increase in lumbar range of motion (P = 0.02) at 6 months.^[11] In contrast Nguyen et al. found that the combination of PRP and SVF in patients with knee OA significantly improved function (WOMAC: Δ–71%, P < 0.05; Lysholm: Δ + 58.5%, P < 0.05) and reduced VAS pain by 75% (P < 0.05) at 18 months, compared to arthroscopic microfracture alone, which showed no significant improvements.^[12]

Other studies on knee OA have shown that MSCs reduced WOMAC scores by 55% (P < 0.001) and VAS pain scores by 50% (P < 0.001), whereas the control group showed no significant changes.^[13]

Studies by Angoorani et al. and Raeissadat et al. analyzed PRP, PRGF, hyaluronic acid, and ozone therapy, demonstrating that PRP and PRGF achieved significant pain reduction (VAS: −41.1–−52.3%, P < 0.001) and improvements in functionality (WOMAC: −36.2–−55.3%, P < 0.001);^[14,15] with greater satisfaction reported in these groups compared to hyaluronic acid and ozone therapy. Finally, compared with Transcutaneous Electrical Nerve Stimulation (TENS) and exercise, PRP significantly increased the time to intolerable pain on a treadmill (P < 0.001) and improved KOOS symptom scores (P = 0.010) at 8 weeks.^[16,17]

These results suggest that PRP- and SC-based therapies may offer superior benefits in pain reduction and functional improvement across various musculoskeletal conditions compared to conventional treatments [Table 1].

To ensure consistency, effect sizes were expressed either as percentage reductions in western ontario and mcmaster universities osteoarthritis index SCORES (WOMAC)/VAS scores or as absolute change (Δ) values whenever possible.

In patients with knee OA, multiple studies reported significant reductions in pain, as measured by the VAS scale, in groups treated with bone marrow aspirate concentrate (BMAC), MSCs, and PRP.^[18] Dulic et al. found that treatment with BMAC resulted in greater short-term pain reduction (P < 0.001) and functional improvement as measured by WOMAC and KOOS, compared to PRP and hyaluronic acid.^[18] LamoEspinosa et al. reported greater pain reduction with Bone Marrow-derived Mesenchymal Stem Cells (BMMSC) + PRGF^® compared to PRGF^® alone (−1.8 vs. −0.5 points on the VAS, P = 0.01).^[19] Similarly, Mormone et al. showed that BMAC obtained from the iliac crest and proximal tibia had a greater impact on pain reduction and functional improvement compared to PRP (P < 0.001 for both VAS and WOMAC).^[20]

Conversely, Bąkowski et al. evaluated the use of fragmented autologous adipose tissue versus PRP, observing improvements in the KOOS, IKDC, and WOMAC scores over a 1-year period.^[21] Mormone et al. and Koh and Choi found that combining adipose-derived MSCs with PRP significantly improved joint function (as measured by the Lysholm and Tegner Activity Scale) and reduced pain compared to PRP alone (P < 0.001).^[20,22]

Another study on rotator cuff tendinopathy has demonstrated that PRP reduces VAS pain by 53.7% (P = 0.023) and improves range of motion at 3 months compared to corticosteroids.^[23] In the treatment of Achilles tendon tendinopathy, Usuelli et al. reported that injection of SVF derived from adipose tissue resulted in a greater reduction in pain (−67.7% vs. −58.7%) and improved function (VISA-A: +113.2% vs. +77%, P < 0.001) compared to PRP.^[24] These findings suggest that biological therapies, particularly those combining MSCs with PRP, may offer superior benefits in pain reduction and functional improvement compared to PRP alone or conventional treatments. However, the heterogeneity in intervention protocols and the lack of studies with low risk of bias highlight the need for more high-quality clinical trials to confirm these results [Table 2].

A high degree of heterogeneity was observed in intervention protocols (e.g., LR-PRP vs. LP-PRP, MSC sources, dosing, and delivery methods) and outcome measures (VAS, WOMAC, KOOS, etc.), which limits the interpretation of pooled data.

Risk of bias analysis in the 23 included studies revealed that a significant proportion had methodological limitations that could compromise the validity of their findings. In total, 10 studies (43.5%) were classified as having a high risk of bias, while the remaining 13 (56.5%) had “some concerns.”

This variability in study quality underscores the need for cautious interpretation of the observed effects [Table 3].

DISCUSSION

The findings of this systematic review highlight the potential of PRP and SC therapies as regenerative strategies for musculoskeletal injuries. Across a range of RCTs, these interventions consistently demonstrated clinically meaningful improvements in pain reduction, joint function, and patient-reported outcomes, particularly in conditions such as knee OA, rotator cuff tendinopathy, and degenerative disc disease (DDD).

These results align with prior meta-analyses and systematic reviews. For instance, Hurley et al. (2019)^[3] found that PRP significantly improved outcomes in arthroscopic rotator cuff repair compared to control groups, while Ding et al. (2021)^[2] showed superior efficacy of intra-articular cell-based therapies over HA or corticosteroids in OA management. Our findings reinforce these conclusions and further suggest that combining PRP with MSCs – particularly BM-MSCs or AD-MSCs – may offer synergistic benefits.

In comparison with conventional modalities, such as NSAIDs, corticosteroid injections, HA, and PT, biological therapies appear to produce more sustained improvements in function and symptom control. For example, several included studies reported greater and longer-lasting reductions in VAS and WOMAC scores with PRP or MSCs versus corticosteroids or HA alone. This suggests that regenerative approaches may address underlying pathology more effectively, rather than merely alleviating symptoms.

However, the significant heterogeneity across studies remains a challenge. Differences were observed in PRP preparation methods (e.g., leukocyte-rich vs. leukocyte-poor PRP, activated vs. non-activated), MSC sources (bone marrow, adipose tissue), cell doses, and delivery routes (injection vs. surgical implantation). These factors likely contribute to the variability in outcomes and complicate comparison across trials.

In addition, nearly half of the included studies were classified as having a high risk of bias. This raises concerns about the internal validity of their results and highlights the necessity for better-designed trials with blinding, larger sample sizes, and longer follow-up periods.

From a translational perspective, practical issues such as the high cost of biologic therapies, lack of standardized preparation protocols, and regulatory variability across regions pose barriers to clinical implementation. Differences in product formulation between centers also pose challenges to reproducibility.

In terms of clinical applicability, PRP and SC therapies may be considered particularly in patients who are refractory to conventional care or those seeking to delay or avoid surgery. Future clinical guidelines should clearly define their role within treatment algorithms for musculoskeletal conditions.

CONCLUSION

This systematic review suggests that both PRP and SC therapies hold promise for treating musculoskeletal injuries. While the magnitude of effect varies, many studies demonstrate improved pain control and functional recovery when compared to conventional therapies. However, methodological limitations and protocol heterogeneity limit the ability to draw definitive conclusions. As such, these biologic treatments should be considered as emerging options with the potential to enhance musculoskeletal repair in selected clinical scenarios.