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The mobilization and effect of endogenous bone marrow progenitor cells in diabetic wound healing

Fiorina, Paolo and Pietramaggiori, Giorgio and Scherer, Saja and Jurewicz, Mollie and Mathews, Jasmine and Vergani, Andrea and Thoma, Gebhard and Orsenigo, Elena and Staudacher, Carlo and La Rosa, Stefano and Capella, Carlo and Carothers, Adelaide and Zerwes, Hans-Guenter and Luzi, Livio and Abdi, Reza and Orgill, Dennis (2011) The mobilization and effect of endogenous bone marrow progenitor cells in diabetic wound healing. Cell Transplantation, 19 (11). pp. 1369-1386. ISSN 0963-6897

Abstract

Diabetic patients suffer from impaired wound healing, characterized by only modest angiogenesis and cell proliferation. Stem cells may stimulate healing, but little is known about the kinetics of mobilization and function of bone marrow progenitor cells (BMPCs) during diabetic wound repair. Objective of this study is to investigate the kinetics of
BM-PC mobilization and their role during early diabetic wound repair in diabetic db/db mice. After wounding, circulating hematopoietic stem cells (Lin-c-Kit+Sca-1+) stably
increased in the periphery and lymphoid tissue of db/db mice compared to unwounded controls. Peripheral endothelial progenitor cells (CD34+VEGFR+) were 2.5- and 3.5-fold
increased on days 6 and 10 after wounding, respectively. Targeting the CXCR4-CXCL12 axis induced an increased release and engraftment of endogenous BM-PCs that was
paralleled by an increased expression of CXCL12/SDF-1α in the wounds. Increased levels of peripheral and engrafted BM-PCs corresponded to stimulated angiogenesis and cell proliferation, while the addition of an agonist (GM-CSF) or an antagonist (ACK2) did not further modulate wound healing. Macroscopic-histological correlations showed that increased levels of stem cells corresponded to higher levels of wound reepithelialization. After wounding, a natural release of endogenous BM-PCs was shown in diabetic mice, but only low levels of these cells homed in the healing tissue. Higher
levels of CXCL12/SDF-1α and circulating stem cells were required to enhance their engraftment and biological effects. Despite controversial data about the functional
impairment of diabetic BM-PCs, in this model our data showed a residual capacity of these cells to trigger angiogenesis and cell proliferation.

Item Type: Article
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Additional Information: The work was done by the external authors, we supplied the CXCR4 antagonist which was used in these studies, associated data and gave input re pharmacology Compound was given out under the MTA The original manuscript was reviewed and released by Patents (G.von Sprecher) in March 2009.
Keywords: CXCR4
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2377

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