Table 2.

Pre-clinical studies using various muscle progenitor cell types in cell therapy approaches for muscular dystrophies

Cell type	Abbreviation	Administration	(Pre-)clinical study	Comments/ pitfalls
Aldehyde dehydrogenase 1A1 cell	ALDH cell	i.m.	Only the CD34- fraction of human ALDH+ cells was myogenic after transplantation in de TA of immunodeficient scid mice [53].	Unclear if systemic delivery is possible, if so, the high proliferative capacity of ALDH cells is positive.
CD133+ (muscle derived) progenitor cell	CD133+ cell	i.m. and i.a.	Genetically corrected CD133+ cells obtained from DMD patients produced dystrophin and recovered muscle morphology and function in immunodeficient mdx mice [55]. Intra-arterially injected autologous engineered canine CD133+ cells restore dystrophin expression in GRMD dogs improving clinical outcome [58].	CD133+ cells are a heterogenous population. Specific subpopulations were used. CD34 to decipher between activated (CD34+) cells and more quiescent (CD34−) cells. CD56, a marker of muscle progenitors, influences the regenerative capacity [57].
Mesenchymal(-like) stem cell	MSC	i.v. and i.m.	MSCs restored cytoplasmic expression of dystrophin, reduced central nucleation, and rescued the expression of mouse mechano growth factor in immunosuppressed mdx mice [63].	MSCs can secrete trophic factors that can influence endogenous mechanisms of tissue regeneration [61]. Anti-inflammatory activity may exert additional positive effects [64].
Mesoangioblast	MAB	i.a.	After a single i.a. injection, SG expression was found in >90% of muscle fibers in the TA muscle of α-SG-null mice. Protein expression was restored to roughly 60% of wild-type levels [122].	Delivery was optimized as MABs were exposed to combined pretreatment with SDF-1 or TNFα and expression of α4 integrin [122].
Muscle-derived stem cell including -Muscle stem cell -Side population cell	MDSC - MuStem cell - SP cell	i.a. and i.m.	MDSCs from normal dog muscle restored some dystrophin expression in myofibers of GRMD dogs, after i.m. or i.a. injection [66]. Murine SP cells exhibited the potential to give rise to both myocytes and SCs after i.m. transplantation into immunodeficient SCID/bg or NOD/scid mice [68, 70].	Heterogenous group of muscle SP cells show low abundance and absence of specific SP cell markers [69]. Further characterization is needed before MDSCs should be considered for therapeutic approaches. The myogenicity of SP cells depends, in some articles, on the presence of myoblasts and/or specific culture conditions [68, 69]. SP cells isolated from dystrophic muscle differentiate along fibro-adipogenic lineage [69].
Myoendothelial cell		i.m.	Human myoendothelial cells injected into immunodeficient scid mice regenerate myofibers. They do so more efficiently than CD56+ myogenic progenitors, which could be partly explained by their faster proliferation rate and higher resistance to oxidative stress, as shown in vitro [72]. Another group used the same name for cells isolated from the mouse endomysium that were able of differentiating into muscle and endothelial cells after transplantation in NOD/shi-scid mice [75].	Human myoendothelial cells did not form hybrid myofibers, but only form de novo fibers [72]. The cell population used could partly consist of SP cells [75].
Pericyte	PC	i.m. or i.a.	GRMD dogs were treated with local or systemic injections of pericytes together with different immunosuppression regimes with steroids. Variable dystrophin expression was observed from different biopsy samples (10%– 70%) for all dogs however, a significant increase in force production in the treated leg was seen [128].	Donor wild-type cells significantly ameliorate symptoms of canine DMD, whereas autologous genetically corrected cells were less effective [128].
PW1+/Pax7- interstitial cell	PIC	i.m.	PICS isolated from mouse or porcine muscles are myogenic in vitro and can contribute to skeletal muscle regeneration in vivo [76, 77].	Enhanced skeletal muscle repair was not caused by a direct fusion of pPICs, since these were eliminated by the host immune system, but rather due to the stimulation of the endogenous stem pool [77].

i.m. intramuscular, i.v. intravenous, i.a. intra-arterial, TA tibialis anterior