Review of the Delivery Route for Mesenchymal Stromal Cells Through Skeletal Muscle

Mesenchymal stromal cells (MSCs) have repeatedly demonstrated the capacity to limit injury and promote regeneration through signaling and secretion of trophic factors. Considering this, MSCs have been increasingly used as a treatment for a wide variety of injuries and immune-related, infectious, and degenerative diseases.  

In this review, Jahromi et al. provide a brief overview of the fate and efficacy of intramuscular (IM) delivered MSCs and identify the gaps that require additional study before IM-delivered MSCs are adopted as a primary treatment of systemic diseases.

Specifically, a recent study has demonstrated significant advantages of using skeletal muscle for the delivery of MSC. While skeletal muscle has been used as a delivery route for myopathic, neurodegenerative, and vascular diseases, these studies have identified 3 main advantages of skeletal muscle MSC delivery. 

These advantages include extended dwell time provided by dense muscle fibers that retain the MSCs in situ; high vascular density that provides a conduit for systemic release of MSC trophic factors; and an abundance of tissue that allows for multiple injection sites.  

Research has identified two key factors that profoundly affect observed dwell-time variations of 72 hours to 8 months observed in MSCs transplanted in the skeletal muscle; these factors include immune rejection and the methods used for MSC detections. Considering this, the authors point out that allotransplantation provides an advantage since MSCs exhibit low immunogenicity and are expected to evade the immune system. 

Although little information on the IM delivery of MSCs currently exists, previously conducted clinical trials demonstrated no therapeutic advantage of using higher doses of MSCs; other studies demonstrated medium doses of MSCs to be more effective than either a lower or higher dose.

While IM-delivery has been shown to be clinically safe and increases the longevity of the secretory activity of the delivered cells, the authors point out that it is important to further evaluate the fate of MSCs post-delivery in skeletal muscle.

Jahromi et al. conclude that the studies reviewed as part of this brief collectively support the notion of broadening the applicability of IM-delivery route from local therapy to the treatment of system disease with multiple studies demonstrating IM-delivered MSCs to be safe and to provide and extended dwell time while remaining secretorily active.

Source:   “Concise Review: Skeletal Muscle as a Delivery Route for … – NCBI.” 5 Feb. 2019, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477141/.