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Animal Bioresource in Japan

.: Home > Animal Bioresource in Japan > 2014 > Volume 63 Number 4 > Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan

A Long-term Follow-up Study on the Engraftment of Human Hematopoietic Stem Cells in Sheep

Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan
engraftment, hematopoietic stem cells, large animal models, long-term follow-up, sheep
Abstract :

Xenograft models of human hematopoiesis are essential to the study of the engraftment and proliferative potential of human hematopoietic stem cells (HSCs) in vivo. Immunodeficient mice and fetal sheep are often used as xenogeneic recipients because they are immunologically naive. In this study, we transplanted human HSCs into fetal sheep and assessed the long-term engraftment of transplanted human HSCs after birth. Fourteen sheep were used in this study. In 4 fetal sheep, HSCs were transduced with homeo-box B4 (HOXB4) gene before transplantation, which promoted the expansion of HSCs. Another 4 fetal sheep were subjected to non-myeloablative conditioning with busulfan. Seven of these 8 sheep showed successful engraftment of human HSCs (1–3% of colony-forming units) as assessed after the birth of fetal sheep (5 months post-transplantation), although HOXB4-transduced HSCs showed sustained engraftment for up to 40 months. Intact HSCs were transplanted into six non-conditioned fetal sheep, and human colony-forming units were not detected in the sheep after birth. These results suggest that, as compared with mouse models, where the short lifespan of mice limits long-term follow-up of HSC engraftment, the fetal sheep model provides a unique perspective for evaluating long-term engraftment and proliferation of human HSCs.

Keywords :
engraftment, hematopoietic stem cells, large animal models, long-term follow-up, sheep

Date Deposited : 07 Apr 2015 16:09

Last Modified : 07 Apr 2015 16:09

Official URL: http://https://www.jstage.jst.go.jp/browse/expanim/62/1/_contents

Volume 63, Number 4, - 2014

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