Functional skeletal muscle regeneration from differentiating embryonic stem cells

Abstract

Little progress has been made toward the use of embryonic stem (ES) cells to study and isolate skeletal muscle progenitors. This is due to the paucity of paraxial mesoderm formation during embryoid body (EB) in vitro differentiation and to the lack of reliable identification and isolation criteria for skeletal muscle precursors. Here we show that expression of the transcription factor Pax3 during embryoid body differentiation enhances both paraxial mesoderm formation and the myogenic potential of the cells within this population. Transplantation of Pax3-induced cells results in teratomas, however, indicating the presence of residual undifferentiated cells. By sorting for the PDGF-alpha receptor, a marker of paraxial mesoderm, and for the absence of Flk-1, a marker of lateral plate mesoderm, we derive a cell population from differentiating ES cell cultures that has substantial muscle regeneration potential. Intramuscular and systemic transplantation of these cells into dystrophic mice results in extensive engraftment of adult myofibers with enhanced contractile function without the formation of teratomas. These data demonstrate the therapeutic potential of ES cells in muscular dystrophy.

Amniotic Fluid Stem Cells Restore the Muscle Cell Niche in a HSA‐Cre , Smn F7/F7 Mouse Model

“…Alternatively, functional myogenic cells can be also derived from embryonic stem cells (ESCs) [34]. Intramuscular and systemic transplantation of Pax3 þ PDGF-aR þ and Flk1 þ ES-derived cells into dystrophic mice results in extensive engraftment of adult myofibers, with enhanced contractile function and no teratoma formation [35]. In order to overcome the immunological problem related to ESCs transplantation, patient-specific induced pluripotent stem (iPS) cells could also be generated [36].…”

“…Only the latter group showed consistently the ability of giving rise to new fibers and that did not differ to the one injected with SCs derived from C57BL/6 GFP þ mice. While SCs have been isolated according to a well-established protocol [10], we are limited by not using a SC lineage tracing mouse for deriving AFS cells [35].…”

Engraftment of mesenchymal stem cells into dystrophin-deficient mice is not accompanied by functional recovery

“…We have demonstrated that Pax3, an essential transcription factor for embryonic muscle specification [53][54][55][56], enables the generation of early skeletal muscle progenitors from differentiating mouse embryonic stem cells [57]. Upon local and systemic transplantation into mdx mice, these cells produce substantial engraftment of adult myofibers, which are endowed with superior contractile function [57].…”

“…Upon local and systemic transplantation into mdx mice, these cells produce substantial engraftment of adult myofibers, which are endowed with superior contractile function [57]. In order to assess whether Pax3 would enable the reprogramming of adult cells towards the myogenic lineage, we began by extending this approach to a mesenchymal stem cell line (MSCB9) derived from adult mouse bone marrow [39].…”

Characterization of porcine partially reprogrammed iPSCs from adipose-derived stem cells

“…As ESCs have high proliferation activity and differentiation potency, they are ideal materials for gene modification (Gropp et al 2003) and regenerative medicine (Darabi et al 2008). Currently, as no bona fide in vitro porcine ESCs are available, porcine iPSCs (PiPSCs) were used as the candidate cells.…”