Human marrow-derived mesodermal progenitor cells generate insulin-secreting islet-like clusters in vivo.
Transplantation of pancreatic islet cells is the only known potential cure for diabetes mellitus. However, the difficulty in obtaining sufficient numbers of purified islets for transplantation severely limits its use. A renewable and clinically accessible source of stem cells capable of differentiating into insulin-secreting beta-cells might circumvent this limitation. Here, we report that human fetal bone marrow (BM)-derived mesodermal progenitor cells (MPCs) possess the potential to generate insulinsecreting islet-like clusters (ISILCs) when injected into human fetal pancreatic tissues implanted in severe combined immunodeficiency (SCID) mice. Seven essential genes involved in pancreatic endocrine development, including insulin, glucagon, somatostatin, pdx-1, glut-2, nkx 2.2, and nkx 6.1, are expressed in these BM-MPC-derived ISILCs, suggesting that ISILCs are generated through neogenesis of BM-MPCs. Our data further suggest that differentiation of BM-MPCs into ISILCs is not mediated by cell fusion. Insulin secretion from these ISILCs is regulated by glucose concentration in vitro, and transplantation of purified ISILCs normalizes hyperglycemia in streptozocin (STZ)- induced nonobese diabetic (NOD)/SCID mice.
Ai
Cuiwei
C
Division of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA 91010-3000, USA.
Todorov
Ivan
I
Slovak
Marilyn L
ML
Digiusto
David
D
Forman
Stephen J
SJ
Shih
Chu-Chih
CC
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002448:Cell Adhesion; D002459:Cell Fusion; D049109:Cell Proliferation; D020732:Cytogenetic Analysis; D005333:Fetus / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology*; D016381:Islets of Langerhans Transplantation; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype; D013234:Stem Cells / Q000166:cytology*
D007328:Insulin; D049452:Green Fluorescent Proteins; D017493:Leukocyte Common Antigens