Stem cells from umbilical cord blood differentiate into myotubes and express dystrophin in vitro only after exposure to in vivo muscle environment.
BACKGROUND
Duchenne muscular dystrophy is a disease characterized by progressive and irreversible muscle degeneration for which there is no therapy. HUCB (human umbilical cord blood) has been considered as an important source of haematopoietic and mesenchymal stem cells, each having been shown to differentiate into distinct cell types. However, it remains unclear if these cells are able to differentiate into muscle cells.


RESULTS
We have showed that stem cells from HUCB did not differentiate into myotubes or express dystrophin when cultured in muscle-conditioned medium or with human muscle cells. However, delivery of GFP (green fluorescent protein)-transduced mononucleated cells from HUCB, which comprises both haematopoietic and mesenchymal populations, into quadriceps muscle of mdx (mouse dystrophy X-chromosome linked) mice resulted in the expression of human myogenic markers. After recovery of these cells from mdx muscle and in vitro cultivation, they were able to fuse and form GFP-positive myotubes that expressed dystrophin.


CONCLUSIONS
These results indicate that chemical factors and cell-to-cell contact provided by in vitro conditions were not enough to trigger the differentiation of stem cells into muscle cells. Nevertheless, we showed that the HUCB-derived stem cells were capable of acquiring a muscle phenotype after exposure to an in vivo muscle environment, which was required to activate the differentiation programme.
Nunes
Viviane A
VA
Human Genome Research Center, Department of Genetics and Evolutionary Biology, University of Sao Paulo, Sao Paulo, SP, Brazil. vanunes@ib.usp.br
Cavaçana
Natale
N
Canovas
Martha
M
Strauss
Bryan E
BE
Zatz
Mayana
M
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D002459:Cell Fusion; D002478:Cells, Cultured; D018920:Coculture Techniques; D016189:Dystrophin / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology*; D019085:Fluorescent Antibody Technique, Direct; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000166:cytology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D013997:Time Factors; D014183:Transplantation, Heterologous
D015415:Biomarkers; D016189:Dystrophin; D049452:Green Fluorescent Proteins