A Promising Future for Stem-Cell-Based Therapies in Muscular Dystrophies—In Vitro and In Vivo Treatments to Boost Cellular Engraftment

Abstract

Muscular dystrophies (MD) are a group of genetic diseases that lead to skeletal muscle wasting and may affect many organs (multisystem). Unfortunately, no curative therapies are available at present for MD patients, and current treatments mainly address the symptoms. Thus, stem-cell-based therapies may present hope for improvement of life quality and expectancy. Different stem cell types lead to skeletal muscle regeneration and they have potential to be used for cellular therapies, although with several limitations. In this review, we propose a combination of genetic, biochemical, and cell culture treatments to correct pathogenic genetic alterations and to increase proliferation, dispersion, fusion, and differentiation into new or hybrid myotubes. These boosted stem cells can also be injected into pretreate recipient muscles to improve engraftment. We believe that this combination of treatments targeting the limitations of stem-cell-based therapies may result in safer and more efficient therapies for MD patients. Matricryptins have also discussed.

Effects of ASC Application on Endplate Regeneration Upon Glycerol-Induced Muscle Damage

“…Necrotic leakage and linked degradative processes can also lead to the loss of dominant cytosolic skeletal muscle proteins, such as f-actin (Huang and Gopalakrishnakone, 1996) and dystrophin (Biral et al, 2000). Muscle fibrosis is characterized by deposition of collagen type I (Gibertini et al, 2014), one of the major components of ECM (Huebner et al, 2008;Serrano and Muñoz-Cánoves, 2010;Gillies and Lieber, 2011;Feng et al, 2019). Following muscle degeneration, muscle recovery involves detection of regenerating myofibers, which are characterized by the expression of embryonic myosin heavy chain (eMHC, also known as myosin 3) (Schiaffino et al, 1986;Murphy et al, 2011;Judson et al, 2013;McDonald et al, 2015;Kastenschmidt et al, 2019) and by nuclei in central position (in the following, referred to as center-nucleated fibers, CNFs) (Judson et al, 2013;McDonald et al, 2015;Arecco et al, 2016;Kastenschmidt et al, 2019).…”

Induced Pluripotent Stem Cells: Hope in the Treatment of Diseases, including Muscular Dystrophies

“…Besides the genetic correction of underlying pathological mutations, these cells can be further treated in culture to boost cell proliferation, long-term survival, dispersion in the muscle, differentiation into muscle fibers, and others. We proposed before the use of multiple combined in vitro treatments for adoptively transferred myoblasts for cell-based therapy, and these are summarized in [101]. These treatments include vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1) and basic fibroblast growth factor (bFGF), Wnt7a, Ursolic acid, and extracellular matrix components.…”

“…Muscular dystrophies (MD) are a group of genetic diseases that lead to skeletal muscle wasting and may affect many organs (multisystem) [101]. The terminal pathology often shows muscle fibers necrosis and muscle tissue replacement by fibrotic or adipose tissues.…”

“…Myoblasts are the progeny of muscle satellite cells (SC), the main stem cell population found in adult skeletal muscles. Quiescent SCs are triggered to reenter into the cell cycle mainly by muscle damage, and the SC-derived myoblasts proliferate and fuse to form new multinucleated myofibers [101]. In most myoblast-based therapies, allogeneic cells were obtained from muscle biopsies from healthy donors, resulting in transplanted cell rejection by the immune system, with low surviving rates, poor dispersion, and differentiation [103][104][105].…”

Systemic cell therapy for muscular dystrophies

“…Collagen is more of a structural component, it improved the self-renewal of SC [147,150]. Several peptides released from ECM proteins called matricryptins have been suggested to be useful in the proliferation, migration, and survival rates of myoblasts [151,152] although specific research is missing.…”