No evidence for significant transdifferentiation of bone marrow into pancreatic beta-cells in vivo.
Several recent studies have suggested that the adult bone marrow harbors cells that can differentiate into tissues from all three germ layers. Other reports have contradicted these findings or attributed them to cell fusion. In this study, we investigated whether bone marrow-derived cells contribute to the renewal of adult pancreatic endocrine cells, in particular insulin-producing beta-cells, in vivo. To address this issue, we studied mice transplanted with green fluorescent protein (GFP)-positive, sex-mismatched bone marrow. We also extended our studies to pancreatic injury models (partial pancreatectomy and streptozotocin administration). All animals showed stable full donor chimerism in the peripheral blood and microscopic analysis at 4-6 weeks and 3 months after transplantation, indicating that the GFP(+) and Y chromosome-positive donor bone marrow contributed substantially to blood, lymphatic, and interstitial cells in the pancreas. However, after examining >100,000 beta-cells, we found only 2 beta-cells positive for GFP, both of which were in control animals without pancreatic injury. Thus our study results did not support the concept that bone marrow contributes significantly to adult pancreatic beta-cell renewal.
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts, USA.
Andreas
A
Lechner
Yong-Guang
YG
Yang
Robyn A
RA
Blacken
Lan
L
Wang
Anna L
AL
Nolan
Joel F
JF
Habener
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D016026:Bone Marrow Transplantation / Q000473:pathology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D005260:Female; D005819:Genetic Markers; D049452:Green Fluorescent Proteins; D007515:Islets of Langerhans / Q000166:cytology*; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010180:Pancreatectomy; D013997:Time Factors; D014184:Transplantation, Homologous
D005819:Genetic Markers; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins