Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression.

Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression. Research Abstract Details 

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Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression. Abstract Text:

L S Kean,A B Adams,E Strobert,R Hendrix,S Gangappa,T R Jones,N Shirasugi,M R Rigby,K Hamby,J Jiang,H Bello,D Anderson,K Cardona,M M Durham,T C Pearson,C P Larsen,

A strategy for producing high-level hematopoietic chimerism after non-myeloablative conditioning has been established in the rhesus macaque. This strategy relies on hematopoietic stem cell transplantation after induction with a non-myeloablative dose of busulfan and blockade of the IL2-receptor in the setting of mTOR inhibition with sirolimus and combined CD28/CD154 costimulation blockade. Hematopoietic stem cells derived from bone marrow and leukopheresis products both were found to be successful in inducing high-level chimerism. Mean peripheral blood peak donor chimerism was 81% with a median chimerism duration of 145 days. Additional immune modulation strategies, such as pre-transplant CD8 depletion, donor-specific transfusion, recipient thymectomy or peritransplant deoxyspergualin treatment did not improve the level or durability of chimerism. Recipient immunologic assessment suggested that chimerism occurred amidst donor-specific down-regulation of alloreactive T cells, and the reappearance of vigorous T-mediated alloreactivity accompanied rejection of the transplants. Furthermore, viral reactivation constituted a significant transplant-related toxicity and may have negatively impacted the ability to achieve indefinite survival of transplanted stem cells. Nevertheless, this chimerism-induction regimen induced amongst the longest-lived stem cell chimerism reported to date for non-human primates and thus represents a platform upon which to evaluate emerging tolerance-induction strategies.

Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression. Publishing Authors By Initials

LS Kean,AB Adams,E Strobert,R Hendrix,S Gangappa,TR Jones,N Shirasugi,MR Rigby,K Hamby,J Jiang,H Bello,D Anderson,K Cardona,MM Durham,TC Pearson,CP Larsen,

For similar biological phenomena, cell phenomena, and immunity: immunity: immune tolerance: transplantation tolerance research abstracts see: biological phenomena, cell phenomena, and immunity: immunity: immune tolerance: transplantation tolerance research

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Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: American journal of transplantation : official jou

VOLUME: 7

Page Numbers: 320-35

Journal Abbreviation: Am. J. Transplant.

ISSN: 1600-6135

DAY: 3

MONTH: Feb

YEAR: 2007

Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100968638

Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression. Keywords Mesh Terms:

KEYWORDS: Transplantation Tolerance

MESH TERMS: immunology

Chemical & Substance for Abstract: Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression. Information

Substance Name: Busulfan

Registry Number: 55-98-1

Grant and Affiliation Information for Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression.

AFFILIATION: The Emory Transplant Center, Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.

Country: Denmark

AGENCY: United States NCRR

GRANT: P51-RR000165-45

ACRONYM: RR

MEDLINETA: Am J Transplant

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