Umbilical cord blood xenografts in immunodeficient mice reveal that T cells enhance hematopoietic engraftment beyond overcoming immune barriers by stimulating stem cell differentiation.

Umbilical cord blood xenografts in immunodeficient mice reveal that T cells enhance hematopoietic engraftment beyond overcoming immune barriers by stimulating stem cell differentiation. Research Abstract Details 

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Umbilical cord blood xenografts in immunodeficient mice reveal that T cells enhance hematopoietic engraftment beyond overcoming immune barriers by stimulating stem cell differentiation. Abstract Text:

Elizabeth O Hexner, Danet-Desnoyers,Yi Zhang,Dale M Frank,James L Riley,Bruce L Levine,David L Porter,Carl H June,Stephen G Emerson,Elizabeth O Hexner, Danet-Desnoyers,Yi Zhang,Dale M Frank,James L Riley,Bruce L Levine,David L Porter,Carl H June,Stephen G Emerson,

Clinical experience and animal models have shown that donor T cell depletion (TCD) adversely affects engraftment of hematopoietic stem cells (HSCs). Although it is known that donor T cells are acting to overcome residual host immune barriers, they may also exert effects independent of host resistance via direct or indirect interactions with donor stem cells, their microenvironment, or key differentiation events. To more precisely define the effect of T cells on engraftment, we have performed human umbilical cord blood (UCB) transplantation into immunodeficient mice under limiting dilution conditions. UCB mononuclear cells (MNC) or TCD UCB were transplanted into NOD/LtSz-scid/scid B2m(null) (NOD/SCID-beta(2)m(-/-)) mice. Cohorts of mice received UCB MNC or TCD UCB at 5 dose levels between 5 x 10(4) and 5 x 10(6) cells. At dose levels at or above 10(5) cells, engraftment was higher in the MNC recipients (n = 32) than the TCD recipients (n = 31) in a dose-dependent manner. Despite this difference, limiting dilution analysis to determine functional stem cell frequency revealed that SCID repopulating cells in TCD UCB was not significantly less than in CB MNCs, suggesting that T cells may facilitate engraftment at stages beyond the stem cell. Add-back of CD3/CD28 costimulated T cells restored and appeared to enhance engraftment, both in NOD/SCID-beta(2)m(-/-) as well as NOD/LtSz-scid IL2Rgamma(null) (NOG) recipients. These results, in a model where there are minimal host immune barriers to overcome, suggest T cells possess additional graft-facilitating properties. CD3/CD28 costimulation of UCB T cells represents a potential strategy for enhancing the engraftment of UCB.

Umbilical cord blood xenografts in immunodeficient mice reveal that T cells enhance hematopoietic engraftment beyond overcoming immune barriers by stimulating stem cell differentiation. Publishing Authors By Initials

EO Hexner,GA Danet-Desnoyers,Y Zhang,DM Frank,JL Riley,BL Levine,DL Porter,CH June,SG Emerson,EO Hexner,GA Danet-Desnoyers,Y Zhang,DM Frank,JL Riley,BL Levine,DL Porter,CH June,SG Emerson,

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Umbilical cord blood xenografts in immunodeficient mice reveal that T cells enhance hematopoietic engraftment beyond overcoming immune barriers by stimulating stem cell differentiation. Journal Published:

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

Journal: Biology of blood and marrow transplantation : jour

VOLUME: 13

Page Numbers: 1135-44

Journal Abbreviation: Biol. Blood Marrow Transplant.

ISSN: 1083-8791

DAY: 24

MONTH: Oct

YEAR: 2007

Umbilical cord blood xenografts in immunodeficient mice reveal that T cells enhance hematopoietic engraftment beyond overcoming immune barriers by stimulating stem cell differentiation. Information

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LANGUAGE: eng

NlmUniqueID: 9600628

Umbilical cord blood xenografts in immunodeficient mice reveal that T cells enhance hematopoietic engraftment beyond overcoming immune barriers by stimulating stem cell differentiation. Keywords Mesh Terms:

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Grant and Affiliation Information for Umbilical cord blood xenografts in immunodeficient mice reveal that T cells enhance hematopoietic engraftment beyond overcoming immune barriers by stimulating stem cell differentiation.

AFFILIATION: Division of Hematology/Oncology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Country: United States

AGENCY: United States NCRR

GRANT: K12 RR017625

ACRONYM: RR

MEDLINETA: Biol Blood Marrow Transplant

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