Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/116585
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Type: Journal article
Title: Induced pluripotent stem cell-derived endothelial cells promote angiogenesis and accelerate wound closure in a murine excisional wound healing model
Author: Clayton, Z.
Tan, R.
Miravet, M.
Lennartsson, K.
Cooke, J.
Bursill, C.
Wise, S.
Patel, S.
Citation: Bioscience Reports, 2018; 38(4):BSR20180563-1-BSR20180563-11
Publisher: Portland Press
Issue Date: 2018
ISSN: 0144-8463
1573-4935
Statement of
Responsibility: 
Zoë E. Clayton, Richard P. Tan, Maria M. Miravet, Katarina Lennartsson, John P. Cooke, Christina A. Bursill, Steven G. Wise, Sanjay Patel
Abstract: 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 × 105) 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.
Keywords: Cells, Cultured; Endothelial Cells; Animals; Mice, Inbred NOD; Humans; Mice, SCID; Wound Healing; Cell Differentiation; Neovascularization, Physiologic; Male; Induced Pluripotent Stem Cells
Rights: © 2018 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY).
RMID: 0030096308
DOI: 10.1042/BSR20180563
Grant ID: http://purl.org/au-research/grants/nhmrc/633283
Appears in Collections:Biochemistry publications

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