Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration

Abstract

Peripheral nerve injuries and neuropathies lead to profound functional deficits. Here, we have demonstrated that muscle-derived stem/progenitor cells (MDSPCs) isolated from adult human skeletal muscle (hMDSPCs) can adopt neuronal and glial phenotypes in vitro and ameliorate a critical-sized sciatic nerve injury and its associated defects in a murine model. Transplanted hMDSPCs surrounded the axonal growth cone, while hMDSPCs infiltrating the regenerating nerve differentiated into myelinating Schwann cells. Engraftment of hMDSPCs into the area of the damaged nerve promoted axonal regeneration, which led to functional recovery as measured by sustained gait improvement. Furthermore, no adverse effects were observed in these animals up to 18 months after transplantation. Following hMDSPC therapy, gastrocnemius muscles from mice exhibited substantially less muscle atrophy, an increase in muscle mass after denervation, and reorganization of motor endplates at the postsynaptic sites compared with those from PBS-treated mice. Evaluation of nerve defects in animals transplanted with vehicle-only or myoblast-like cells did not reveal histological or functional recovery. These data demonstrate the efficacy of hMDSPC-based therapy for peripheral nerve injury and suggest that hMDSPC transplantation has potential to be translated for use in human neuropathies.

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery

“…If compared, their results of approximately 450 axons recovered in the ruptured sciatic nerve and 50% retention of downstream muscle mass are apparently less than the values of the non-cell transplanted media control group in the present study. Nonetheless, previous and present studies have collectively demonstrated that skeletal muscles are important and practical cell sources for nerve repair [9, 15–17]. Similarly, several human adult somatic stem cell lines, such as human hair follicle stem cells [22], human umbilical cord-derived mesenchymal stem cells [23], and human bone marrow stromal cells [24], have been applied to the regeneration of damaged peripheral nerves, and their cellular differentiation capacities have been examined in vivo .…”

“…Another group has reported similar differentiation and therapeutic capacity using human muscle-derived stem cells [15]. The isolated cells demonstrated neuronal and glial phenotypes in vitro and ameliorated a critical-sized sciatic nerve injury after in vivo transplantation into the SCID mouse model, showing differentiation into Schwann cells.…”

“…Human skeletal muscle-derived stem cells (Sk-SCs) have been isolated, characterized, and examined with respect to their in vivo differentiation capacities [10–14]. However, the therapeutic application of human Sk-SCs to nerve repair has never been investigated, even though they are thought to be involved in nerve regeneration [15]. We also studied the optimal methods for the therapeutic isolation and fractionation of human skeletal muscle-derived cells (Sk-Cs), and established appropriate cell expansion culture methods [16].…”

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth

“…Various types of transplanted stem cells were shown to enhance peripheral nerve regeneration in preclinical animal studies of nerve reconstruction. A variety of cell types, such as bone marrow stromal cells, adipose-derived stromal cells, muscle-derived stem cells, and dental pulp stem cells, were applied to this approach [17][18][19][20][21][22][23][24]. However, recent studies have reported low transplanted stem cell survival rates.…”

Stem cells, the current state of researches on this problem and the main directions of their development. From theory to clinical practice

“…Больше того, было установлено, что эффективным может быть даже ксеногенный клеточный материал. Введение мышам человече-ских прекьюсорных клеток обусловливало развитие у подопытных животных регенерации аксонов при участии донорских клеток [20].…”