HB-EGF augments the ability of mesenchymal stem cells to attenuate intestinal injury

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• 作者：Daniel J. Watkins ; Yu Zhou ; Mika A.B. Matthews ; Li Chen ; Gail E. Besner ; ^{gail.besner@nationwidechildrens.org" class="auth_mail}
• 关键词：Heparin-binding EGF-like growth factor ; Mesenchymal stem cells ; Bone marrow ; Amniotic fluid ; Ischemia/reperfusion ; Intestinal injury
• 刊名：Journal of Pediatric Surgery
• 出版年：June 2014
• 年：2014
• 卷：49
• 期：6
• 页码：938-944
• 全文大小：860 K

文摘

We have previously demonstrated that heparin-binding EGF-like growth factor (HB-EGF) and mesenchymal stem cell (MSC) administration protect the intestines from ischemia/reperfusion (I/R) injury in vivo, with amniotic fluid-derived MSC (AF-MSC) being more efficacious than bone marrow-derived MSC (BM-MSC). The goal of the current study was to determine whether the protective effects of HB-EGF were from direct effects on MSC or via alternative mechanisms.

bsSec_2">Methods

Murine MSC were transfected with an HB-EGF plasmid or control plasmid by electroporation. Mice were subjected to segmental intestinal I/R injury and received either BM-MSC or AF-MSC either with or without exogenous HB-EGF, or BM-MSC or AF-MSC that endogenously over-expressed HB-EGF. MSC engraftment, intestinal histologic injury, and intestinal permeability were quantified.

bsSec_3">Results

There was increased MSC engraftment into injured compared to uninjured intestine. HB-EGF increased AF-MSC engraftment into injured intestine. Administration of HB-EGF and MSC improved intestinal histology and intestinal permeability after I/R injury, with AF-MSC being most efficacious. The effect of HB-EGF on MSC was similar when the growth factor was administered exogenously, or when it was overexpressed endogenously.

bsSec_4">Conclusions

The effect of HB-EGF on AF-MSC was similar with both exogenous administration and endogenous overexpression of the growth factor, implying that HB-EGF has a direct effect on AF-MSC. This information may assist in guiding potential future AF-MSC-based therapies for patients at risk of intestinal ischemic injuries.