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Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts

Standard

Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. / Swijnenburg, Rutger Jan; Schrepfer, Sonja; Govaert, Johannes A.; Cao, Feng; Ransohoff, Katie; Sheikh, Ahmad Y.; Haddad, Munif; Connolly, Andrew J.; Davis, Mark M.; Robbins, Robert C.; Wu, Joseph C.

in: P NATL ACAD SCI USA, Jahrgang 105, Nr. 35, 02.09.2008, S. 12991-12996.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Swijnenburg, RJ, Schrepfer, S, Govaert, JA, Cao, F, Ransohoff, K, Sheikh, AY, Haddad, M, Connolly, AJ, Davis, MM, Robbins, RC & Wu, JC 2008, 'Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts', P NATL ACAD SCI USA, Jg. 105, Nr. 35, S. 12991-12996. https://doi.org/10.1073/pnas.0805802105

APA

Swijnenburg, R. J., Schrepfer, S., Govaert, J. A., Cao, F., Ransohoff, K., Sheikh, A. Y., Haddad, M., Connolly, A. J., Davis, M. M., Robbins, R. C., & Wu, J. C. (2008). Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. P NATL ACAD SCI USA, 105(35), 12991-12996. https://doi.org/10.1073/pnas.0805802105

Vancouver

Swijnenburg RJ, Schrepfer S, Govaert JA, Cao F, Ransohoff K, Sheikh AY et al. Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts. P NATL ACAD SCI USA. 2008 Sep 2;105(35):12991-12996. https://doi.org/10.1073/pnas.0805802105

Bibtex

@article{b4a963c633a745e78a8e40d96212ae74,
title = "Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts",
abstract = "Given their self-renewing and pluripotent capabilities, human embryonic stem cells (hESCs) are well poised as a cellular source for tissue regeneration therapy. However, the host immune response against transplanted hESCs is not well characterized. In fact, controversy remains as to whether hESCs have immune-privileged properties. To address this issue, we used in vivo bioluminescent imaging to track the fate of transplanted hESCs stably transduced with a double-fusion reporter gene consisting of firefly luciferase and enhanced GFP. We show that survival after transplant is significantly limited in immunocompetent as opposed to immunodeficient mice. Repeated transplantation of hESCs into immunocompetent hosts results in accelerated hESC death, suggesting an adaptive donor-specific immune response. Our data demonstrate that transplanted hESCs trigger robust cellular and humoral immune responses, resulting in intragraft infiltration of inflammatory cells and subsequent hESC rejection. Moreover, we have found CD4+ T cells to be an important modulator of hESC immune-mediated rejection. Finally, we show that immunosuppressive drug regimens can mitigate the anti-hESC immune response and that a regimen of combined tacrolimus and sirolimus therapies significantly prolongs survival of hESCs for up to 28 days. Taken together, these data suggest that hESCs are immunogenic, trigger both cellular and humoral-mediated pathways, and, as a result, are rapidly rejected in xenogeneic hosts. This process can be mitigated by a combined immunosuppressive regimen as assessed by molecular imaging approaches.",
keywords = "Immunological response, Immunosuppression, Molecular imaging",
author = "Swijnenburg, {Rutger Jan} and Sonja Schrepfer and Govaert, {Johannes A.} and Feng Cao and Katie Ransohoff and Sheikh, {Ahmad Y.} and Munif Haddad and Connolly, {Andrew J.} and Davis, {Mark M.} and Robbins, {Robert C.} and Wu, {Joseph C.}",
year = "2008",
month = sep,
day = "2",
doi = "10.1073/pnas.0805802105",
language = "English",
volume = "105",
pages = "12991--12996",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "35",

}

RIS

TY - JOUR

T1 - Immunosuppressive therapy mitigates immunological rejection of human embryonic stem cell xenografts

AU - Swijnenburg, Rutger Jan

AU - Schrepfer, Sonja

AU - Govaert, Johannes A.

AU - Cao, Feng

AU - Ransohoff, Katie

AU - Sheikh, Ahmad Y.

AU - Haddad, Munif

AU - Connolly, Andrew J.

AU - Davis, Mark M.

AU - Robbins, Robert C.

AU - Wu, Joseph C.

PY - 2008/9/2

Y1 - 2008/9/2

N2 - Given their self-renewing and pluripotent capabilities, human embryonic stem cells (hESCs) are well poised as a cellular source for tissue regeneration therapy. However, the host immune response against transplanted hESCs is not well characterized. In fact, controversy remains as to whether hESCs have immune-privileged properties. To address this issue, we used in vivo bioluminescent imaging to track the fate of transplanted hESCs stably transduced with a double-fusion reporter gene consisting of firefly luciferase and enhanced GFP. We show that survival after transplant is significantly limited in immunocompetent as opposed to immunodeficient mice. Repeated transplantation of hESCs into immunocompetent hosts results in accelerated hESC death, suggesting an adaptive donor-specific immune response. Our data demonstrate that transplanted hESCs trigger robust cellular and humoral immune responses, resulting in intragraft infiltration of inflammatory cells and subsequent hESC rejection. Moreover, we have found CD4+ T cells to be an important modulator of hESC immune-mediated rejection. Finally, we show that immunosuppressive drug regimens can mitigate the anti-hESC immune response and that a regimen of combined tacrolimus and sirolimus therapies significantly prolongs survival of hESCs for up to 28 days. Taken together, these data suggest that hESCs are immunogenic, trigger both cellular and humoral-mediated pathways, and, as a result, are rapidly rejected in xenogeneic hosts. This process can be mitigated by a combined immunosuppressive regimen as assessed by molecular imaging approaches.

AB - Given their self-renewing and pluripotent capabilities, human embryonic stem cells (hESCs) are well poised as a cellular source for tissue regeneration therapy. However, the host immune response against transplanted hESCs is not well characterized. In fact, controversy remains as to whether hESCs have immune-privileged properties. To address this issue, we used in vivo bioluminescent imaging to track the fate of transplanted hESCs stably transduced with a double-fusion reporter gene consisting of firefly luciferase and enhanced GFP. We show that survival after transplant is significantly limited in immunocompetent as opposed to immunodeficient mice. Repeated transplantation of hESCs into immunocompetent hosts results in accelerated hESC death, suggesting an adaptive donor-specific immune response. Our data demonstrate that transplanted hESCs trigger robust cellular and humoral immune responses, resulting in intragraft infiltration of inflammatory cells and subsequent hESC rejection. Moreover, we have found CD4+ T cells to be an important modulator of hESC immune-mediated rejection. Finally, we show that immunosuppressive drug regimens can mitigate the anti-hESC immune response and that a regimen of combined tacrolimus and sirolimus therapies significantly prolongs survival of hESCs for up to 28 days. Taken together, these data suggest that hESCs are immunogenic, trigger both cellular and humoral-mediated pathways, and, as a result, are rapidly rejected in xenogeneic hosts. This process can be mitigated by a combined immunosuppressive regimen as assessed by molecular imaging approaches.

KW - Immunological response

KW - Immunosuppression

KW - Molecular imaging

UR - http://www.scopus.com/inward/record.url?scp=51349086014&partnerID=8YFLogxK

U2 - 10.1073/pnas.0805802105

DO - 10.1073/pnas.0805802105

M3 - SCORING: Journal article

C2 - 18728188

AN - SCOPUS:51349086014

VL - 105

SP - 12991

EP - 12996

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 35

ER -