Neonatal immune-tolerance in mice does not prevent xenograft rejection.
Assessing the efficacy of human stem cell transplantation in rodent models is complicated by the significant immune rejection that occurs. Two recent reports have shown conflicting results using neonatal tolerance to xenografts in rats. Here we extend this approach to mice and assess whether neonatal tolerance can prevent the rapid rejection of xenografts. In three strains of neonatal immune-intact mice, using two different brain transplant regimes and three independent stem cell types, we conclusively show that there is rapid rejection of the implanted cells. We also address specific challenges associated with the generation of humanized mouse models of disease.
Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Virginia B
VB
Mattis
Rush University, Chicago, IL, USA.
Dustin R
DR
Wakeman
Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Colton
C
Tom
Rush University, Chicago, IL, USA.
Hemraj B
HB
Dodiya
University of California-Irvine, Irvine, CA, USA.
Sylvia Y
SY
Yeung
University of California-Irvine, Irvine, CA, USA.
Andrew H
AH
Tran
University of Wisconsin-Madison, Madison, WI, USA.
Ksenija
K
Bernau
Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Loren
L
Ornelas
Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Anais
A
Sahabian
University of California-Irvine, Irvine, CA, USA.
Jack
J
Reidling
Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Dhruv
D
Sareen
University of California-Irvine, Irvine, CA, USA.
Leslie M
LM
Thompson
Rush University, Chicago, IL, USA.
Jeffrey H
JH
Kordower
Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: Clive.Svendsen@cshs.org.
Clive N
CN
Svendsen
D000818:Animals; D000831:Animals, Newborn; D021461:Animals, Outbred Strains; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology; D004195:Disease Models, Animal; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000276:immunology; D064593:Heterografts / Q000276:immunology*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D007108:Immune Tolerance / Q000276:immunology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics; D058953:Neural Stem Cells / Q000276:immunology* / Q000637:transplantation*; D009687:Nuclear Proteins / Q000235:genetics; D014183:Transplantation, Heterologous
C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins
Huntington's disease; Immune rejection; Neonatal immunity; Neonatal tolerance; Xenograft