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

• ABE Tomoyuki

  Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan University Farm, Department of Agriculture, Utsunomiya University, 443 Shimokomoriya, Mouka-shi, Tochigi 321-4415, Japan

• HANAZONO Yutaka

  Division of Regenerative Medicine, Center for Molecular Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan CREST, Japan Science and Technology Agency, 5-3 Yonbancho, Chiyoda-ku, Tokyo 102-8666, Japan

• NAGAO Yoshikazu

  University Farm, Department of Agriculture, Utsunomiya University, 443 Shimokomoriya, Mouka-shi, Tochigi 321-4415, Japan

Bibliographic Information

Other Title

• 10.1538/expanim.63.475
• Long-term follow-up study on the engraftment of human hematopoietic stem cells in 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.

Journal

• Experimental Animals

  Experimental Animals 63 (4), 475-481, 2014

  Japanese Association for Laboratory Animal Science

Keywords

• engraftment
• hematopoietic stem cells
• large animal models
• long-term follow-up
• sheep

Details

• CRID: 1390001205047220864
• NII Article ID: 130005089324
• NII Article ID: 130004701642
• NII Book ID: AA11032321
• DOI: 10.1538/expanim.14-0036
• DOI: 10.1538/expanim.63.475
• ISSN: 18817122
• ISSN: 00075124
• ISSN: 13411357
• NDL BIB ID: 025857967
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I025857967
• Web Site: https://www.jstage.jst.go.jp/article/expanim/63/4/63_14-0036/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2015248371
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed