Normal Relationship of β- and Non–β-Cells Not Needed for Successful Islet Transplantation
Aileen J.F. King 1 2 3 ,
Justin R. Fernandes 1 ,
Jennifer Hollister-Lock 1 ,
Cameron E. Nienaber 1 ,
Susan Bonner-Weir 1 2 and
Gordon C. Weir 1 2
1 Section on Islet Transplantation and Cell Biology, Research Division, Joslin Diabetes Center, Boston, Massachusetts
2 Department of Medicine, Harvard Medical School, Boston, Massachusetts
3 Division of Reproduction and Endocrinology, Guy's Campus, King's College London, United Kingdom
Address correspondence and reprint requests to Gordon C. Weir, MD, Section on Islet Transplantation and Cell Biology, Joslin
Diabetes Center, One Joslin Place, Boston, MA 02215. E-mail: gordon.weir{at}joslin.harvard.edu
Abstract
Islets are composed mostly of β-cells, and therefore stem cell research has concentrated on generating purified β-cells, neglecting
the other endocrine cell types in the islet. We investigated the presence of endocrine non–β-cells after islet transplantation.
In addition, we studied whether the transplantation of pure β-cells, in volumes similar to that used in islet transplantation,
would suffice to reverse hyperglycemia in diabetic mice. Rat islets were dispersed and β-cells were purified by fluorescence-activated
cell sorting according to their endogenous fluorescence. After reaggregation, 600 islet equivalents of the purified β-cell
aggregates were implanted into diabetic SCID mice. In mice implanted with β-cell–enriched aggregates, the hyperglycemia was
reversed and good graft function over a 12-week period was observed with regard to glucose and insulin levels, glucose tolerance
tests, and graft insulin content. The endocrine cell composition of the β-cell–enriched aggregates remained constant; before
and 12 weeks after transplantation, the β-cell–enriched aggregates comprised 95% β-cells and 5% endocrine non–β-cells. However,
islet grafts, despite originally having comprised 75% β-cells and 25% endocrine non–β-cells, comprised just 5% endocrine non–β-cells
after transplantation, indicating a loss of these cells. β-Cell–enriched aggregates can effectively reverse hyperglycemia
in mice, and transplanted intact islets are depleted in non–β-cells. It is therefore likely that islet non–β-cells are not
essential for successful islet transplantation.
IE, islet equivalent
IPGTT, intraperitoneal glucose tolerance test
Footnotes
Published ahead of print at http://diabetes.diabetesjournals.org on 11 June 2007. DOI: 10.2337/db07-0191.
A.J.F.K. and J.R.F. contributed equally to this work.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted J...

Normal Relationship of β- and Non–β-Cells Not Needed for Successful Islet Transplantation

10.2337/db07-0191