Mesenchymal stem/stromal cells generated from induced pluripotent stem cells are highly resistant to senescence
概要
Mesenchymal stem/stromal cells (MSCs) are stem cells that exhibit self-renewal and differentiation potential, defined by their osteogenic, chondrogenic, and adipogenic properties and
surface markers.1 MSCs exist in vivo in the bone marrow, adipose tissue, and umbilical cord.
The use of MSCs has attracted attention in the field of regenerative medicine owing to their
anti-inflammatory effects and tissue repair-enhancing effects via proliferation of progenitor cells,
angiogenesis, and anti-apoptotic effects. We have also demonstrated the therapeutic effects of
MSCs in nephritis and acute kidney injury.2-4
As advances in clinical applications of MSCs have progressed, several critical issues have
emerged. First, cellular senescence is a concern in the clinical application of MSCs, since it
has been reported in vitro that MSCs have a decreased proliferation rate5 and a decreased differentiation potential6 with further cell passaging. Second, cellular heterogeneity is a potential
bottleneck in ensuring sufficient cell numbers for therapy. MSCs exhibit different proliferative and
differentiation capacities depending on their source.7-9 As a possible solution to these problems,
MSCs can be generated from induced pluripotent stem cells (iPSCs).10-13 iPSC-derived MSCs
(iMSCs) are expected to represent a new source of MSCs based on the possibility of obtaining
a large amount of cells showing relatively high uniformity and low invasiveness in cell harvesting. Therefore, we investigated the characteristics of iMSCs. We determined whether cellular
senescence observed in normal MSCs is overcome in iMSCs since there are few studies that
evaluate cellular senescence. In the present study, we successfully demonstrated that iMSCs are
more resistant to cellular senescence than bone marrow-derived MSCs (BM-MSCs) by staining
cells with fluorescein di-b-D-galactopyranoside (FDG), which can quantitatively evaluate the
cellular senescence,14 after continuous passaging and analyzing cell proliferation potential and
cell morphology. ...