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Advancing animal models of human type 1 diabetes by engraftment of functional human tissues in immunodeficient mice.

Authors
  • Brehm, Michael A
  • Powers, Alvin C
  • Shultz, Leonard D
  • Greiner, Dale L
Type
Published Article
Journal
Cold Spring Harbor Perspectives in Medicine
Publisher
Cold Spring Harbor Laboratory
Publication Date
May 01, 2012
Volume
2
Issue
5
Identifiers
DOI: 10.1101/cshperspect.a007757
PMID: 22553498
Source
Medline
License
Unknown

Abstract

Despite decades of studying rodent models of type 1 diabetes (T1D), no therapy capable of preventing or curing T1D has successfully been translated from rodents to humans. This inability to translate otherwise promising therapies to clinical settings likely resides, to a major degree, from significant species-specific differences between rodent and human immune systems as well as species-related variances in islets in terms of their cellular composition, function, and gene expression. Indeed, taken collectively, these differences underscore the need to define interactions between the human immune system with human β cells. Immunodeficient mice engrafted with human immune systems and human β cells represent an interesting and promising opportunity to study these components in vivo. To meet this need, years of effort have been extended to develop mice depleted of undesirable components while at the same time, allowing the introduction of constituents necessary to recapitulate physiological settings as near as possible to human T1D. With this, these so-called "humanized mice" are currently being used as a preclinical bridge to facilitate identification and translation of novel discoveries to clinical settings.

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