HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Online-Only Appendix All Versions of this Article: db08-0244v1 57/9/2402    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miller, R. Articles by Crisa, L. Search for Related Content PubMed PubMed Citation Articles by Miller, R. Articles by Crisa, L. Social Bookmarking                What's this?

Switching-on Survival and Repair Response Programs in Islet Transplants by Bone Marrow-derived Vasculogenic Cells

¹Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA
²Department of Pediatrics and
³Department of Medicine, Biomedical Genomics Microarray Facility (BIOGEM), University of California San Diego, La Jolla, CA
⁴The Sloan Kettering Cancer Center, New York, NY

Objective: Vascular progenitors of bone marrow (BM) origin participate to neo-vascularization at sites of wound healing and transplantation. We hypothesized that the biological purpose of this BM-derived vascular component is to contribute angiogenic and survival functions distinct from those provided by the local tissue-derived vasculature.

Research Design and Results: To address this hypothesis, we investigated the functional impact of BM-derived vascular cells on pancreatic islets engraftment using BM-reconstituted Id+/–Id3–/– mice, a model of BM-derived vasculogenesis. We show that, in this model, BM-derived vasculogenic cells primarily contribute to the formation of new blood vessels within islet transplants. In contrast, grafts re-vascularization in a wild type background occurs by tissue-derived blood vessels only. Using these distinct transplant models in which BM- and tissue-derived vasculature are virtually mutually exclusive, we demonstrate that BM-derived vasculogenic cells exhibit enhanced angiogenic functions and support prompt activation of islets survival pathways which significantly impact on islets engraftment and function. Moreover, gene profiling of vascular and inflammatory cells of the grafts demonstrate that neo-vascularization by BM-derived cells is accompanied by the activation of a genetic program uniquely tuned to down-regulate harmful inflammatory responses and promote tissue repair.

Conclusions: These studies uncover the biological significance of BM-derived vasculogenic cells in the response to injury during transplantation. Enhancing the contribution of BM-derived vasculogenic cells to transplantation sites may help to overcome both limited angiogenic responses of the adult tissue-derived vasculature and untoward effects of inflammation on transplant engraftment.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Brissova and A. C. Powers Revascularization of Transplanted Islets: Can It Be Improved? Diabetes, September 1, 2008; 57(9): 2269 - 2271. [Full Text] [PDF]