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

This Article Full Text Full Text (PDF) 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 Google Scholar Google Scholar Articles by Bogdani, M. Articles by Pipeleers, D. Search for Related Content PubMed PubMed Citation Articles by Bogdani, M. Articles by Pipeleers, D. Social Bookmarking                What's this?

Growth and Functional Maturation of ß-Cells in Implants of Endocrine Cells Purified From Prenatal Porcine Pancreas

¹ Diabetes Research Center, Brussels Free University and Juvenile Diabetes Research Foundation Center for Beta Cell Therapy in Diabetes, Brussels, Belgium
² Research Laboratory for Stereology and Neuroscience, H:S Bispebjerg Hospital, University Hospital of Copenhagen, Denmark

The development of islet cell transplantation as a cure for diabetes is limited by the shortage of human donor organs. Moreover, currently used grafts exhibit a marginal ß-cell mass with an apparently low capacity for ß-cell renewal and growth. Although duct-associated nonendocrine cells have often been suggested as a potential source for ß-cell production, recent work in mice has demonstrated the role of ß-cells in postnatal growth of the pancreatic ß-cell mass. The present study investigated whether the ß-cell mass can grow in implants that are virtually devoid of nonendocrine cells. Endocrine islet cells were purified from prenatal porcine pancreases (gestation >110 days) and implanted under the kidney capsule of nude mice. ß-Cells initially presented with signs of immaturity: small size, low insulin content, undetectable C-peptide release, and an inability to correct hyperglycemia. They exhibited a proliferative activity that was highest during posttransplant week 1 (2.6 and 5% bromodeoxyuridine [BrdU]-positive ß-cells 4 and 72 h posttransplant) and then decreased over 20 weeks to rates measured in the pancreas (0.2% BrdU-positive cells). ß-Cell proliferation in implants first compensated for ß-cell loss during posttransplant week 1 and then increased the ß-cell number fourfold between posttransplant weeks 1 and 20. Rates of -cell proliferation were only shortly and moderately increased, which explained the shift in cellular composition of the implant (ß-cell 40 vs. 90% and -cell 40 vs. 7% at the start and posttransplant week 20, respectively). ß-Cells progressively matured during the 20 weeks after transplantation, with a twofold increase in cell volume, a sixfold increase in cellular insulin content, plasma C-peptide levels of 1–2 ng/ml, and an ability to correct diabetes. They became structurally organized as homogenous clusters with their secretory vesicles polarized toward fenestrated capillaries. We concluded that the immature ß-cell phenotype provides grafts with a marked potential for ß-cell growth and differentiation and hence may have a potential role in curing diabetes. Cells with this phenotype can be isolated from prenatal organs; their presence in postnatal organs needs to be investigated.

Abbreviations: BrdU, bromodeoxyuridine; CK-7, cytokeratin

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