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Intramuscular (IM) administration of perinatal-derived mesenchymal stem/stromal cells (MSCs) is a novel therapeutic strategy designed to deliver regenerative, anti-inflammatory, and immunomodulatory effects directly into skeletal muscle tissue. Unlike intra-articular therapy, IM delivery targets muscle architecture, where MSCs may enhance angiogenesis, modulate fibrosis, and promote repair of injured or degenerative muscle fibers. The paracrine signaling profile of perinatal MSCs makes them especially attractive for conditions involving chronic myopathy, ischemia, or post-traumatic muscle damage.
Perinatal stem cell IM therapy may be considered in patients with:
Chronic muscle injuries (hamstring, calf, rotator cuff, quadriceps) not responding to conventional rehabilitation.
Myopathies of metabolic or inflammatory origin where adjunctive biologics may aid repair.
Peripheral artery disease–related ischemic myopathy (as studied in critical limb ischemia trials).
Postsurgical muscle loss or fibrosis (following orthopedic or tendon repair).
Adjunctive use in sports medicine for enhanced recovery in carefully selected athletes.
Greatest potential is in patients with persistent pain, weakness, or MRI-confirmed muscle pathology where conservative care has failed.
Patient Selection
Ideal candidates include:
Adults with documented muscle pathology confirmed by MRI, ultrasound, or EMG.
Patients with refractory pain or weakness despite physical therapy, NSAIDs, and standard biologics (e.g., PRP).
Non-smokers and metabolically optimized patients (BMI <35, controlled diabetes).
Patients with realistic expectations—therapy supports tissue recovery but does not guarantee full regeneration.
Contraindications
IM stem cell therapy should be avoided in:
Active infection at the injection site or systemic infection.
Advanced neuromuscular disorders with irreversible denervation (e.g., late-stage ALS).
History of malignancy in the injected region.
Uncontrolled autoimmune or systemic inflammatory disease.
Severe coagulopathy or patients on anticoagulants (risk of hematoma).
Pregnancy or breastfeeding (safety data insufficient).
Relative MSC dosing is influenced by muscle size, vascularity, and extent of pathology:
Small muscle groups (intrinsic foot muscles, hand muscles): 2–5 million viable MSCs.
Medium muscle groups (calf, hamstrings, rotator cuff, biceps): 10–20 million viable MSCs.
Large muscle groups (quadriceps, gluteal, paraspinals): 30–50 million viable MSCs.
Injections are typically distributed across multiple sites within the target muscle to ensure even coverage and prevent localized overconcentration.
Important note: Intramuscular stem cell injections require precise anatomical knowledge and image guidance (ultrasound or fluoroscopy) to avoid neurovascular injury, inadvertent tendon injection, or compartment syndrome. Practitioners must be trained and comfortable with musculoskeletal injection techniques to reduce risks.
Conclusion
Intramuscular delivery of perinatal MSCs is an emerging regenerative option for patients with chronic muscle pathology, myopathy, or ischemia-related weakness. By leveraging the paracrine signaling and trophic factors of perinatal MSCs, this therapy may promote angiogenesis, reduce fibrosis, and enhance functional recovery. Careful patient selection, appropriate dosing by muscle group, and technical expertise in musculoskeletal injections are essential to optimize outcomes and minimize risk.
References
Murphy MP, Wang H, Patel AN, Kambhampati S, Angle N, Chan K, et al. Allogeneic endometrial regenerative cells: An ‘off the shelf solution’ for critical limb ischemia? J Transl Med. 2008;6:45. doi:10.1186/1479-5876-6-45
Lawall H, Bramlage P, Amann B. Stem cell and progenitor cell therapy in peripheral artery disease: A critical appraisal. Thromb Haemost. 2010;103(4):696–709. doi:10.1160/TH09-07-0500
Lopa S, Colombini A, Moretti M, de Girolamo L. Injective mesenchymal stem cell-based treatments for tendon and muscle injuries: A narrative review. Biomed Res Int. 2019;2019:2371217. doi:10.1155/2019/2371217
Saini A, Al-Shanti N, Stewart CE. Waste management—Cytokines, growth factors and cachexia. Cytokine Growth Factor Rev. 2006;17(6):475–86. doi:10.1016/j.cytogfr.2006.09.001
Matas J, Orrego M, Amenabar D, Infante C, Tapia-Limonchi R, Cadiz MI, et al. Umbilical cord-derived mesenchymal stromal cells in musculoskeletal regenerative medicine. Stem Cells Transl Med. 2019;8(6):504–13. doi:10.1002/sctm.18-0121
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