Hematopoietic stem cells derived from adult donors are not a source of pancreatic beta-cells in adult nondiabetic humans.
OBJECTIVE
Type 1 and type 2 diabetes are characterized by an approximately 98 and approximately 65% loss of pancreatic beta-cells, respectively. Efforts to reverse either form of diabetes increasingly focus on the possibility of promoting beta-cell replacement and/or regeneration. Islet transplantation has been explored, but it does not provide long-term insulin independence. One possible source of beta-cell regeneration is hematopoietic stem cells. In mice, there are conflicting data as to whether hematopoietic stem cells contribute to pancreatic beta-cells. We sought to establish whether hematopoietic stem cells (derived from adult donors) transdifferentiate into pancreatic beta-cells in adult humans.


METHODS
We addressed this in 31 human pancreata obtained at autopsy from hematopoietic stem cell transplant recipients who had received their transplant from a donor of the opposite sex.


RESULTS
Whereas some donor-derived cells were observed in the nonendocrine pancreata, no pancreatic beta-cells were identified that were derived from donor hematopoietic stem cells, including two cases with type 2 diabetes.


CONCLUSIONS
We conclude that hematopoietic stem cells derived from adult donors contribute minimally to pancreatic beta-cells in nondiabetic adult humans. These data do not rule out the possibility that hematopoietic stem cells contribute to pancreatic beta-cells in childhood or in individuals with type 1 diabetes.
Butler
Alexandra E
AE
University of California Los Angeles, Larry L. Hillblom Islet Research Center, 900 Veteran Ave., Los Angeles, CA 90095-7073, USA.
Huang
Andrew
A
Rao
P Nagesh
PN
Bhushan
Anil
A
Hogan
William J
WJ
Rizza
Robert A
RA
Butler
Peter C
PC
D000328:Adult; D003924:Diabetes Mellitus, Type 2; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000502:physiology*; D012038:Regeneration