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Endothelial cells direct mesenchymal stem cells toward a smooth muscle cell fate.

ABSTRACT: Under defined conditions, mesenchymal stem cells can differentiate into unique cell types, making them attractive candidates for cell-based disease therapies. Ischemic diseases would greatly benefit from treatments that include the formation of new blood vessels from mesenchymal stem cells. However, blood vessels are complex structures composed of endothelial cells and smooth muscle cells, and their assembly and function in a diseased environment is reliant upon joining with the pre-existing vasculature. Although endothelial cell/smooth muscle cell interactions are well known, how endothelial cells may influence mesenchymal stem cells and facilitate their differentiation has not been defined. Therefore, we sought to explore how endothelial cells might drive mesenchymal stem cells toward a smooth muscle fate. Our data show that cocultured endothelial cells induce smooth muscle cell differentiation in mesenchymal stem cells. Endothelial cells can promote a contractile phenotype, reduce proliferation, and enhance collagen synthesis and secretion. Our data show that Notch signaling is essential for endothelial cell-dependent differentiation, and this differentiation pathway is largely independent of growth factor signaling mechanisms.

SUBMITTER: Lin CH

PROVIDER: S-EPMC4201243 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Endothelial cells direct mesenchymal stem cells toward a smooth muscle cell fate.

Lin Cho-Hao CH Lilly Brenda B

Stem cells and development 20140714 21

Under defined conditions, mesenchymal stem cells can differentiate into unique cell types, making them attractive candidates for cell-based disease therapies. Ischemic diseases would greatly benefit from treatments that include the formation of new blood vessels from mesenchymal stem cells. However, blood vessels are complex structures composed of endothelial cells and smooth muscle cells, and their assembly and function in a diseased environment is reliant upon joining with the pre-existing vas ...[more]

PMID: 24914692

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Project description:Oligodendrogenesis encompasses lineage specification of neural progenitor cells (NPCs) and differentiation into oligodendrocytes that ultimately culminates in the myelination of central nervous system axons. Each individual process must be tightly regulated by extracellular and cell-intrinsic mechanisms, whose identities are barely understood. We had previously demonstrated that soluble factors derived from rat mesenchymal stem cells (MSCs) induce oligodendrogenesis in differentiating adult NPCs under differentiation conditions. However, since lineage specification predominantly occurs in proliferating progenitors and not necessarily during early differentiation, we investigated if soluble factors derived from MSCs are able to prime NPCs to the oligodendroglial fate already under proliferation conditions. Therefore, we analyzed the effects of a 3 weeks stimulation of adult NPCs under proliferation conditions with conditioned media derived from MSCs (MSC-CM) in terms of cell morphology, proliferation, cell-specific marker expression profile, response to growth factor withdrawal (GFW), cell-lineage restriction, and expression of glial fate determinants. While MSC-CM did not affect the proliferation rate of NPCs, it boosted the formation of 2', 3'-cyclic-nucleotide-3'-phosphodieesterase (CNPase)- and myelin basic protein-expressing oligodendrocytes after GFW, even when cells were exposed to an astrogenic milieu. Moreover, it reinforced the proper development of oligodendrocytes, since it ensured a sustained expression of the functional marker CNPase. Finally, the presence of MSC-CM reduced the anti-oligodendrogenic determinant Id2 in proliferating NPCs, thus increasing the relative proportion of the pro-oligodendrogenic factor Olig2 expression. In summary, MSCs prime proliferating progenitors and, thus, reinforce cell fate choice and accelerate differentiation toward the oligodendrocyte lineage. The present findings underscore the potential use of MSCs in cell therapies for remyelination such as in multiple sclerosis and spinal cord injury. Moreover, they urge the identification of the oligodendrogenic activity(ies) derived from MSCs to develop novel molecular therapies for demyelinating diseases.

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Endothelial cells direct mesenchymal stem cells toward a smooth muscle cell fate.

Publications

Endothelial cells direct mesenchymal stem cells toward a smooth muscle cell fate.

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