Lack of CD47 on Donor Hepatocytes Promotes Innate Immune Cell Activation and Graft Loss: A Potential Barrier to Hepatocyte Xenotransplantation

Author:

Navarro-Alvarez Nalu12,Yang Yong-Guang12

Affiliation:

1. Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY, USA

2. Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Abstract

We have previously shown that interspecies incompatibility of CD47 plays an important role in triggering rejection of xenogeneic hematopoietic cells by macrophages. However, whether CD47 incompatibility also induces rejection of nonhematopoietic cellular xenografts remains unknown. Herein, we have addressed this question in a mouse model of hepatocyte transplantation in which CD47-/- hepatocytes were used to resemble xenografts for CD47 incompatibility. We show that intrasplenic transplantation of CD47-/-, but not wild-type (WT) hepatocytes, into partially hepatectomized syngeneic WT mice resulted in a rapid increase in Mac-1+ cells with an activation phenotype (i.e., Mac-1+CD14+ and Mac-1+CD16/32high), compared to nontransplant controls. In addition, CD47-/- hepatocytes were more severely damaged than WT hepatocytes as indicated by the greater AST and ALT serum levels in these mice. Furthermore, long-term donor hepatocyte survival and liver repopulation were observed in mice receiving WT hepatocytes, whereas CD47-/- hepatocytes were completely rejected within 2 weeks. These results suggest that CD47 on donor hepatocytes prevents recipient myeloid innate immune cell activation, hence aiding in graft survival after hepatocyte transplantation. Thus, CD47 incompatibility is likely to present an additional barrier to hepatocyte xenotransplantation.

Publisher

SAGE Publications

Subject

Transplantation,Cell Biology,Biomedical Engineering

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3