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Induced pluripotent stem cell-derived endothelial cells promote angiogenesis and accelerate wound closure in a murine excisional wound healing mode
Heart Res Inst, Australia.
Heart Res Inst, Australia; Univ Sydney, Australia.
Linköping University, Faculty of Medicine and Health Sciences. Heart Res Inst, Australia.
Linköping University, Faculty of Medicine and Health Sciences. Heart Res Inst, Australia.
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2018 (English)In: Bioscience Reports, ISSN 0144-8463, E-ISSN 1573-4935, Vol. 38, article id BSR20180563Article in journal (Refereed) Published
Abstract [en]

Chronic wounds are a major complication in patients with cardiovascular diseases. Cell therapies have shown potential to stimulate wound healing, but clinical trials using adult stem cells have been tempered by limited numbers of cells and invasive procurement procedures. Induced pluripotent stem cells (iPSCs) have several advantages of other cell types, for example they can be generated in abundance from patients somatic cells (autologous) or those from a matched donor. iPSCs can be efficiently differentiated to functional endothelial cells (iPSC-ECs). Here, we used a murine excisional wound model to test the pro-angiogenic properties of iPSC-ECs in wound healing. Two full-thickness wounds were made on the dorsum of NOD-SCID mice and splinted. iPSC-ECs (5 x 10(5)) were topically applied to one wound, with the other serving as a control. Treatment with iPSC-ECs significantly increased wound perfusion and accelerated wound closure. Expression of endothelial cell (EC) surface marker, platelet endothelial cell adhesion molecule (PECAM-1) (CD31), and pro-angiogenic EC receptor, Tie1, mRNA was up-regulated in iPSC-EC treated wounds at 7 days post-wounding. Histological analysis of wound sections showed increased capillary density in iPSC-EC wounds at days 7 and 14 post-wounding, and increased collagen content at day 14. Anti-GFP fluorescence confirmed presence of iPSC-ECs in the wounds. Bioluminescent imaging (BLI) showed progressive decline of iPSC-ECs over time, suggesting that iPSC-ECs are acting primarily through short-term paracrine effects. These results highlight the pro-regenerative effects of iPSC-ECs and demonstrate that they are a promising potential therapy for intractable wounds.

Place, publisher, year, edition, pages
PORTLAND PRESS LTD , 2018. Vol. 38, article id BSR20180563
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:liu:diva-152835DOI: 10.1042/BSR20180563ISI: 000449560000043PubMedID: 29976773OAI: oai:DiVA.org:liu-152835DiVA, id: diva2:1265201
Note

Funding Agencies|National Health and Medical Research Council (NHMRC) Early Career Fellowship [GNT0633283]

Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2018-11-22

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