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Derivation of hepatocytes from bone marrow cells in mice after radiation‐induced myeloablation
Author(s) -
Theise Neil D.,
Badve Sunil,
Saxena Romil,
Henegariu Octavian,
Sell Stewart,
Crawford James M.,
Krause Diane S.
Publication year - 2000
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510310135
Subject(s) - bone marrow , cd34 , pathology , biology , transplantation , medicine , liver injury , haematopoiesis , liver regeneration , stem cell , regeneration (biology) , endocrinology , microbiology and biotechnology
Abstract Following a report of skeletal muscle regeneration from bone marrow cells, we investigated whether hepatocytes could also derive in vivo from bone marrow cells. A cohort of lethally irradiated B6D2F1 female mice received whole bone marrow transplants from age‐matched male donors and were sacrificed at days 1, 3, 5, and 7 and months 2, 4, and 6 posttransplantation (n = 3 for each time point). Additionally, 2 archival female mice of the same strain who had previously been recipients of 200 male fluorescence‐activated cell sorter (FACS)‐sorted CD34 + lin − cells were sacrificed 8 months posttransplantation under the same protocol. Fluorescence in situ hybridization (FISH) for the Y‐chromosome was performed on liver tissue. Y‐positive hepatocytes, up to 2.2% of total hepatocytes, were identified in 1 animal at 7 days posttransplantation and in all animals sacrificed 2 months or longer posttransplantation. Simultaneous FISH for the Y‐chromosome and albumin messenger RNA (mRNA) confirmed male‐derived cells were mature hepatocytes. These animals had received lethal doses of irradiation at the time of bone marrow transplantation, but this induced no overt, histologically demonstrable, acute hepatic injury, including inflammation, necrosis, oval cell proliferation, or scarring. We conclude that hepatocytes can derive from bone marrow cells after irradiation in the absence of severe acute injury. Also, the small subpopulation of CD34 + lin − bone marrow cells is capable of such hepatic engraftment.