Background Musculoskeletal disorders are one of the most common causes that lead to disability throughout the world and routinely present with only limited or short-term symptom relief following traditional treatments. Recent developments, such as platelet-rich plasma (PRP) and mesenchymal stem/stromal cell (MSC) interventions, are being used as regenerative biologic adjuncts in musculoskeletal medicine, yet significant variability exists in preparation strategies, activation methods, and dosing protocols. In addition, clinical interpretation remains limited by inconsistent biologic characterization and protocol variability. Objective A comprehensive review of current clinical evidence regarding dosing parameters, activation methods, and functional outcomes of PRP and MSC therapies for musculoskeletal recovery, focusing on protocol variability and clinical reproducibility. Methods A structured literature search was conducted using predefined search terms in PubMed, BMJ Journals, and SpringerLink to identify human clinical studies evaluating platelet-rich plasma and mesenchymal stem cell therapies for musculoskeletal conditions. Studies published between January 2016 and December 2025 were screened. An updated search extending through December 31, 2025 identified additional records published after February 2025; however, none met the predefined inclusion criteria. Results Five controlled trials featuring PRP or MSC techniques met inclusion criteria. Significant heterogeneity was observed across studies in biologic preparation techniques, leukocyte content, activation methods, cell expansion protocols, dosing regimens, and follow-up duration. While improvements in pain and functional scores were reported across both types of interventions, dose-response relationships were inconsistently evaluated and direct protocol comparisons were limited. Conclusion Although regenerative biologic therapies such as PRP and MSC are associated with improvements in musculoskeletal rehabilitation, significant variability and inconsistent reporting in dosing, activation, and preparation limit generalizability and reproducibility. Prospective clinical trials featuring standardized biologic characterization and uniform reporting frameworks are necessary to begin defining evidence-informed dosing recommendations and rehabilitation delivery.
Obaid et al. (Wed,) studied this question.