(Journal Article): No evidence for significant transdifferentiation of bone marrow into pancreatic beta-cells in vivo.
Lechner A, Yang YG, Blacken RA, Wang L, Nolan AL, Habener JF (Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts, USA.)
IN:
Diabetes
2004; 53(3):616-623
Impact Factor(s) of Diabetes: 8.848 (2004), 8.298 (2003), 8.256 (2002), 7.7 (2001)
ABSTRACT: 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.
TYPE OF PUBLICATION: Original article
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(Journal Article): Cell fusion is the principal source of bone-marrow-derived hepatocytes.
Wang X, Willenbring H, Akkari Y, Torimaru Y, Foster M, Al-Dhalimy M, Lagasse E, Finegold M, Olson S, Grompe M (Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, Oregon 97239, USA.)
IN:
Nature
2003; 422(6934):897-901
Impact Factor(s) of Nature: 29.273 (2005), 32.182 (2004), 30.979 (2003), 30.432 (2002), 27.955 (2001)
ABSTRACT: Evidence suggests that haematopoietic stem cells might have unexpected developmental plasticity, highlighting therapeutic potential. For example, bone-marrow-derived hepatocytes can repopulate the liver of mice with fumarylacetoacetate hydrolase deficiency and correct their liver disease. To determine the underlying mechanism in this murine model, we performed serial transplantation of bone-marrow-derived hepatocytes. Here we show by Southern blot analysis that the repopulating hepatocytes in the liver were heterozygous for alleles unique to the donor marrow, in contrast to the original homozygous donor cells. Furthermore, cytogenetic analysis of hepatocytes transplanted from female donor mice into male recipients demonstrated 80,XXXY (diploid to diploid fusion) and 120,XXXXYY (diploid to tetraploid fusion) karyotypes, indicative of fusion between donor and host cells. We conclude that hepatocytes derived form bone marrow arise from cell fusion and not by differentiation of haematopoietic stem cells.
TYPE OF PUBLICATION: Original article
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