TY - JOUR
T1 - The repopulation potential of hepatocyte populations differing in size and prior mitotic expansion
AU - Overturf, Ken
AU - Al-Dhalimy, Muhsen
AU - Finegold, Milton
AU - Grompe, Markus
N1 - Funding Information:
Supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant DK 51592 (to M. G. and M. F.) and NIDDK National Research Service Award DK009429 (to K. O.).
PY - 1999/12
Y1 - 1999/12
N2 - Recently the stem cell-like regenerative potential of adult liver cells was demonstrated by serial transplantation. This repopulation capacity could be useful for the treatment of genetic liver diseases by cell transplantation and/or expansion of genetically manipulated cells. However, previous experiments used unfractionated populations of liver cells, and therefore it remained undetermined whether all hepatocytes or only a subpopulation (stem cells) possessed this high regenerative ability. To address this question we used centrifugal elutriation to separate hepatocytes by cell density. Unexpectedly, small hepatocytes (16 μm) had lower repopulation capacity during the first round of transplantation when compared with both the medium- sized (21 μm) and large (27 μm) cells. We also compared the repopulation capacity of hepatocytes that had undergone different degrees of in vivo expansion. Previous cell division neither reduced nor increased the repopulation capacity of transplanted liver cells. Finally, retroviral tagging experiments demonstrated that liver-repopulating cells occur at a frequency of > 1:10,000. We conclude that short-term therapeutic liver repopulation does not require progenitor or stem cells.
AB - Recently the stem cell-like regenerative potential of adult liver cells was demonstrated by serial transplantation. This repopulation capacity could be useful for the treatment of genetic liver diseases by cell transplantation and/or expansion of genetically manipulated cells. However, previous experiments used unfractionated populations of liver cells, and therefore it remained undetermined whether all hepatocytes or only a subpopulation (stem cells) possessed this high regenerative ability. To address this question we used centrifugal elutriation to separate hepatocytes by cell density. Unexpectedly, small hepatocytes (16 μm) had lower repopulation capacity during the first round of transplantation when compared with both the medium- sized (21 μm) and large (27 μm) cells. We also compared the repopulation capacity of hepatocytes that had undergone different degrees of in vivo expansion. Previous cell division neither reduced nor increased the repopulation capacity of transplanted liver cells. Finally, retroviral tagging experiments demonstrated that liver-repopulating cells occur at a frequency of > 1:10,000. We conclude that short-term therapeutic liver repopulation does not require progenitor or stem cells.
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U2 - 10.1016/S0002-9440(10)65531-9
DO - 10.1016/S0002-9440(10)65531-9
M3 - Article
C2 - 10595942
AN - SCOPUS:0032805945
SN - 0002-9440
VL - 155
SP - 2135
EP - 2143
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -