DNA sequences from a primate-specific CMT element

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Hepatology. 2009 Jun 15.

Hepatic targeting and biodistribution of human fetal liver stem/progenitor cells

and adult hepatocytes in mice.

Cheng K, Benten D, Bhargava K, Inada M, ph B, Palestro C, Gupta S.

n Bessin Liver Research Center, Diabetes Research Center, and Cancer

Research Center, Departments of Medicine and Pathology, Albert Einstein College

of Medicine, Bronx, NY.

Tracking stem/progenitor cells through noninvasive imaging is a helpful means of

assessing the targeting of transplanted cells to specific organs. We performed

in vitro and in vivo studies wherein adult human hepatocytes and human fetal

liver stem/progenitor cells were labeled with indium-111 ((111)In)-oxine and

technetium-99m ((99m)Tc)-Ultratag or (99m)Tc-Ceretec. The labeling efficiency

and viability of cells was analyzed in vitro, and organ biodistribution of cells

was analyzed in vivo after transplantation in xenotolerant nonobese

diabetic/severe combined immunodeficiency mice through intrasplenic or

intraportal routes. We found that adult hepatocytes and fetal liver

stem/progenitor cells incorporated (111)In but not (99m)Tc labels. After

radiolabeling, cell viability was unchanged. Transplanted adult hepatocytes or

fetal liver stem/progenitor cells were targeted to the liver more effectively by

the intraportal rather than the intrasplenic route. Transplanted cells were

retained in the liver after intraportal injection and in the liver and spleen

after intrasplenic injection, without translocations into pulmonary or systemic

circulations. Compared with fetal liver stem/progenitor cells, fewer adult

hepatocytes were retained in the spleen after intrasplenic transplantation.

The distribution of transplanted cells in organs was substantiated by genetic

assays, including polymerase chain reaction amplification of DNA sequences from

a primate-specific Charcot-Marie-Tooth element, and in situ hybridization for

primate alphoid satellite sequences ubiquitous in all centromeres.

Conclusion: (111)In labeling of human fetal liver stem/progenitor cells and

adult hepatocytes was effective for noninvasive localization of transplanted

cells. This should facilitate continued development of cell therapies through

further animal and clinical studies.