Interspecies Organogenesis for Human Transplantation

Andrew T. Crane, Rajagopal N. Aravalli, Atsushi Asakura, Andrew W. Grande, Venkatramana D. Krishna, Daniel F. Carlson, Maxim C.J. Cheeran, Georgette Danczyk, James R. Dutton, Perry B. Hackett, Wei Shou Hu, Ling Li, Wei Cheng Lu, Zachary D. Miller, Timothy D. O’Brien, Angela Panoskaltsis-Mortari, Ann M. Parr, Clairice Pearce, Mercedes Ruiz-Estevez, Maple ShiaoChristopher J. Sipe, Nikolas G. Toman, Joseph Voth, Hui Xie, Clifford J. Steer, Walter C. Low

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Blastocyst complementation combined with gene editing is an emerging approach in the field of regenerative medicine that could potentially solve the worldwide problem of organ shortages for transplantation. In theory, blastocyst complementation can generate fully functional human organs or tissues, grown within genetically engineered livestock animals. Targeted deletion of a specific gene(s) using gene editing to cause deficiencies in organ development can open a niche for human stem cells to occupy, thus generating human tissues. Within this review, we will focus on the pancreas, liver, heart, kidney, lung, and skeletal muscle, as well as cells of the immune and nervous systems. Within each of these organ systems, we identify and discuss (i) the common causes of organ failure; (ii) the current state of regenerative therapies; and (iii) the candidate genes to knockout and enable specific exogenous organ development via the use of blastocyst complementation. We also highlight some of the current barriers limiting the success of blastocyst complementation.

Original languageEnglish (US)
Pages (from-to)1091-1105
Number of pages15
JournalCell transplantation
Volume28
Issue number9-10
DOIs
StatePublished - Sep 1 2019

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study is supported in part by National Institute of Diabetes and Digestive and Kidney Diseases Grant 1R01DK117286-01 to C. J. Steer.

Funding Information:
The authors wish to acknowledge Marra Evans who contributed illustrations for the figures. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study is supported in part by National Institute of Diabetes and Digestive and Kidney Diseases Grant 1R01DK117286-01 to C. J. Steer.

Publisher Copyright:
© The Author(s) 2019.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • blastocyst complementation
  • development
  • gene editing
  • organ bioengineering
  • transplantation

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