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J Invest Dermatol. 2019 Mar;139(3):692-701. doi: 10.1016/j.jid.2018.08.031. Epub 2018 Oct 28.

Reconstituting Human Cutaneous Regeneration in Humanized Mice under Endothelial Cell Therapy.

Author information

1
Department of Medicine, Sungkyunkwan University School of Medicine, Kyunggi, Republic of Korea; Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea; APR Lab Inc, Seoul, Republic of Korea.
2
Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea; BYON Co Ltd, Stem Cell Research Center, Seoul, Republic of Korea.
3
Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea.
4
Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea; Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea.
5
Department of Stem Cell Biology, School of Medicine, Konkuk University, Seoul, Republic of Korea; Mirae Cell Bio Co Ltd, Seoul, Republic of Korea.
6
Soonchunhyang Institute of Medi-Bio Science, College of Medicine, Soon Chun Hyang University, Cheonan, Republic of Korea. Electronic address: leeman@sch.ac.kr.
7
Stem Cell and Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea; Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Republic of Korea; Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: kmhyj.kim@samsung.com.
8
Department of Medicine, School of Medicine, Konkuk University, Seoul, Republic of Korea. Electronic address: sunghwanmoon@kku.ac.kr.

Abstract

Much of our understanding of human biology and the function of mammalian cells in tissue regeneration have been derived from mechanistically and genetically manipulated rodent models. However, current models examining epidermal wound repair fail to address both the cross-species mechanistic and immunogenic differences simultaneously. Herein, we describe a multifaceted approach intended to better recapitulate human skin recovery in rodent models. First, immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice were intravenously inoculated with human hematopoietic stem cells to become, in essence, humanized, and capable of initiating an adaptive immune response. Next, a chimney-shaped mechanical device was implanted onto the excisional wound site to prevent healing by primary intention (contraction) and expedite cell transplantation. Subsequently, cell therapy was administered by transplanting cord blood-derived endothelial progenitor cells or human pluripotent stem cell-derived endothelial cells into the wound site to examine the regeneration process at a histological level. This study demonstrates human cutaneous repair in a murine model by addressing both the mechanistic and immunogenic differences in the epidermis. We further show human leukocyte recruitment in damaged tissue and improved healing by secondary intention in the transplanted groups, highlighting the need for useful preclinical animal models to better understand leukocyte function in human (tissue repair and) regeneration.

PMID:
30393080
DOI:
10.1016/j.jid.2018.08.031
[Indexed for MEDLINE]
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