Journal
STEM CELLS
Volume 32, Issue 3, Pages 694-705Publisher
WILEY-BLACKWELL
DOI: 10.1002/stem.1538
Keywords
Spheroids; Neovascularization; Fibronectin; Platelet-derived growth factor receptor; Endothelial; Mesenchymal stromal cells
Categories
Funding
- Medical Research Council (U.K.) [G0902170]
- British Heart Foundation
- MRC [G0701165, G0902170] Funding Source: UKRI
- Medical Research Council [G0902170, G0701165] Funding Source: researchfish
Ask authors/readers for more resources
Realizing the full therapeutic potential of mesenchymal stromal/stem cells (MSCs) awaits improved understanding of mechanisms controlling their fate. Using MSCs cultured as spheroids to recapitulate a three-dimensional cellular environment, we show that perturbing the mesenchymal regulators, platelet-derived growth factor (PDGF) receptors or fibronectin, reverts MSCs toward mesodermal progenitors with endothelial potential that can potently induce neovascularization in vivo. MSCs within untreated spheroids retain their mesenchymal spindle shape with abundant smooth muscle alpha-actin filaments and fibronectin-rich matrix. Inhibiting PDGF receptors or depleting fibronectin induces rounding and depletes smooth muscle alpha-actin expression; these cells have characteristics of mesenchymoangioblasts, with enhanced expression of mesendoderm and endoderm transcription factors, prominent upregulation of E-cadherin, and Janus kinase signaling-dependent expression of Oct4A and Nanog. PDGF receptor-inhibited spheroids also upregulate endothelial markers platelet endothelial cell adhesion molecule 1 and vascular endothelial-cadherin and secrete many angiogenic factors, and in vivo they potently stimulate neovascularization, and their MSCs integrate within functional blood vessels that are perfused by the circulation. Thus, MSC potency and vascular induction are regulated by perturbing mesenchymal fate. Stem Cells 2014;32:694-705
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available