Enhanced Mmyogenic potential of mesoangioblast-derived induced pluripotent stem cells

M. Quattrocelli, G. Palazzolo, I. Perini, L. Thorrez, E. Berardi, Marinee Chuah, Thierry VandenDriessche, M. Sampaolesi

Research output: Contribution to journalEditorial

Abstract

Mesoangioblasts (MABs) are a myogenic subset of pericytes,
present in the adult skeletal muscles of mice, dogs and humans.
MABs can migrate and efficiently engraft into chronically damaged
fibres of dystrophic murine and canine muscles. However,
MAB expansion is limited by senescence after 15-20 passages.
Induced pluripotent stem cells (iPSCs) constitute a novel frontier
in the regenerative medicine. iPSCs are obtained from somatic
cells via overexpression of a combination of pluripotency-related
transcription factors and/or microRNAs. iPSCs share many aspects
with embryonic stem cells (ESCs), e.g. wide differentiation
potency and vast proliferation capacity, and circumvent ESCrelated
ethical issues. Nevertheless, iPSCs should still carefully be
investigated before a real clinical application, in order to avoid
teratomas and to efficiently achieve in vivo regeneration. Recently,
iPSCs were generated from murine MABs (MAB-iPSCs), through
retroviral overexpression of Oct4, Sox2, Klf4 and cMyc. MABiPSCs
were comparable to fibroblast-derived iPSCs (f-iPSCs) and
to ESCs in morphology, pluripotency marker expression and
teratoma formation ability. Strikingly, MAB-iPSC-derived teratomas
showed 70% of striated muscle tissue (5% in f-iPSC teratomas).
Moreover, flanking regions of myogenic markers were
hypomethylated in MAB-iPSCs, as compared to f-iPSCs. In A24 ORAL ABSTRACTS
addition, following transient transfection with Pax3 and Pax7,
MAB-iPSCs yielded in vitro, at a higher rate than f-iPSCs, CD56+
myogenic progenitors. MAB-iPSC-derived CD56+ and CD56-
cells were intramuscularly injected into tibialis anterior muscles of
asg-null dystrophic mice. Only CD56+ progenitors did robustly
engraft into severely damaged fibres, partially recovering asg
expression and reconstituting, even if rarely, the satellite cell pool.
Original languageEnglish
Pages (from-to)24-25
Number of pages2
JournalHum Gene Ther
Volume22
Issue numberOctober
Publication statusPublished - 2011

Keywords

  • stem cells

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