Back to Search
Start Over
Efficient engraftment of pluripotent stem cell-derived myogenic progenitors in a novel immunodeficient mouse model of limb girdle muscular dystrophy 2I
- Source :
- Skeletal Muscle, Skeletal Muscle, Vol 10, Iss 1, Pp 1-13 (2020)
- Publication Year :
- 2020
- Publisher :
- BioMed Central, 2020.
-
Abstract
- Background Defects in α-dystroglycan (DG) glycosylation characterize a group of muscular dystrophies known as dystroglycanopathies. One of the key effectors in the α-DG glycosylation pathway is the glycosyltransferase fukutin-related protein (FKRP). Mutations in FKRP lead to a large spectrum of muscular dystrophies, including limb girdle muscular dystrophy 2I (LGMD2I). It remains unknown whether stem cell transplantation can promote muscle regeneration and ameliorate the muscle wasting phenotype associated with FKRP mutations. Results Here we transplanted murine and human pluripotent stem cell-derived myogenic progenitors into a novel immunodeficient FKRP-mutant mouse model by intra-muscular injection. Upon both mouse and human cell transplantation, we observe the presence of donor-derived myofibers even in absence of pre-injury, and the rescue of α-DG functional glycosylation, as shown by IIH6 immunoreactivity. The presence of donor-derived cells expressing Pax7 under the basal lamina is indicative of satellite cell engraftment, and therefore, long-term repopulation potential. Functional assays performed in the mouse-to-mouse cohort revealed enhanced specific force in transplanted muscles compared to PBS-injected controls. Conclusions Altogether, our data demonstrate for the first time the suitability of a cell-based therapeutic approach to improve the muscle phenotype of dystrophic FKRP-mutant mice.
- Subjects :
- 0301 basic medicine
Pluripotent Stem Cells
lcsh:Diseases of the musculoskeletal system
Cell
Muscle Fibers, Skeletal
Mice, SCID
Biology
03 medical and health sciences
Mice
0302 clinical medicine
Mice, Inbred NOD
Muscle regeneration
medicine
Animals
Humans
Orthopedics and Sports Medicine
Pentosyltransferases
Muscular dystrophy
Progenitor cell
Induced pluripotent stem cell
Dystroglycans
Molecular Biology
Cells, Cultured
Transplantation
Research
LGMD2I
PAX7 Transcription Factor
Cell Differentiation
Cell Biology
Genetic Therapy
medicine.disease
Cell biology
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Muscular Dystrophies, Limb-Girdle
PAX7
Stem cell
lcsh:RC925-935
030217 neurology & neurosurgery
FKRP
Limb-girdle muscular dystrophy
Stem Cell Transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 20445040
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Skeletal Muscle
- Accession number :
- edsair.doi.dedup.....e59439df25dad5e791ff3fea61c7ee2d