Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats

Ali Emre Aksu, Elaine Horibe, Justin Michael Sacks, Ryosuke Ikeguchi, Jeremy Breitinger, Merissa Scozio, Jignesh Unadkat, Maryam Feili-Hariri

Research output: Contribution to journalArticle

Abstract

We investigated the effect of autologous mesenchymal stem cells (MSC) on multiple unmodified donor bone marrow (BM) infusions and vascularized skin graft outcome. BM-derived rat MSC were examined for phenotype and function. MSC/MSC-conditioned-medium suppressed IFN-γ production by T cells and modified DC function. Infusions of MSC with one-time BM improved vascularized skin graft survival, while with one-two-times BM reversed graft versus host disease (GVHD). Mixed chimerism was enhanced in recipients given two-four-times BM with MSC infusions. Interestingly, four-times BM infusions with MSC delayed GVHD onset, reduced host tissue damage and enhanced vascularized skin allograft survival compared to four-times BM alone. These data demonstrate that, the co-infusion of MSC with unmodified BM limit the toxicity of allogeneic BM transplantation, enhance mixed chimerism and improve vascularized skin graft survival. These findings provide insights for the development of autologous MSC-based BM transplantation and prevention of graft rejection or treatment of autoimmunity.

Original languageEnglish (US)
Pages (from-to)348-358
Number of pages11
JournalClinical Immunology
Volume127
Issue number3
DOIs
StatePublished - Jun 2008
Externally publishedYes

Fingerprint

Graft vs Host Disease
Mesenchymal Stromal Cells
Allografts
Bone Marrow
Skin
Chimerism
Graft Survival
Bone Marrow Transplantation
Homologous Transplantation
Graft Rejection
Conditioned Culture Medium
Autoimmunity
T-Lymphocytes
Transplants
Phenotype

Keywords

  • Bone marrow
  • GVHD
  • Mesenchymal stem cells
  • Rat
  • Vascularized skin

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats. / Aksu, Ali Emre; Horibe, Elaine; Sacks, Justin Michael; Ikeguchi, Ryosuke; Breitinger, Jeremy; Scozio, Merissa; Unadkat, Jignesh; Feili-Hariri, Maryam.

In: Clinical Immunology, Vol. 127, No. 3, 06.2008, p. 348-358.

Research output: Contribution to journalArticle

Aksu, Ali Emre ; Horibe, Elaine ; Sacks, Justin Michael ; Ikeguchi, Ryosuke ; Breitinger, Jeremy ; Scozio, Merissa ; Unadkat, Jignesh ; Feili-Hariri, Maryam. / Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats. In: Clinical Immunology. 2008 ; Vol. 127, No. 3. pp. 348-358.
@article{32b21531a1d84f54a17b085c04d69b9d,
title = "Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats",
abstract = "We investigated the effect of autologous mesenchymal stem cells (MSC) on multiple unmodified donor bone marrow (BM) infusions and vascularized skin graft outcome. BM-derived rat MSC were examined for phenotype and function. MSC/MSC-conditioned-medium suppressed IFN-γ production by T cells and modified DC function. Infusions of MSC with one-time BM improved vascularized skin graft survival, while with one-two-times BM reversed graft versus host disease (GVHD). Mixed chimerism was enhanced in recipients given two-four-times BM with MSC infusions. Interestingly, four-times BM infusions with MSC delayed GVHD onset, reduced host tissue damage and enhanced vascularized skin allograft survival compared to four-times BM alone. These data demonstrate that, the co-infusion of MSC with unmodified BM limit the toxicity of allogeneic BM transplantation, enhance mixed chimerism and improve vascularized skin graft survival. These findings provide insights for the development of autologous MSC-based BM transplantation and prevention of graft rejection or treatment of autoimmunity.",
keywords = "Bone marrow, GVHD, Mesenchymal stem cells, Rat, Vascularized skin",
author = "Aksu, {Ali Emre} and Elaine Horibe and Sacks, {Justin Michael} and Ryosuke Ikeguchi and Jeremy Breitinger and Merissa Scozio and Jignesh Unadkat and Maryam Feili-Hariri",
year = "2008",
month = "6",
doi = "10.1016/j.clim.2008.02.003",
language = "English (US)",
volume = "127",
pages = "348--358",
journal = "Clinical Immunology",
issn = "1521-6616",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats

AU - Aksu, Ali Emre

AU - Horibe, Elaine

AU - Sacks, Justin Michael

AU - Ikeguchi, Ryosuke

AU - Breitinger, Jeremy

AU - Scozio, Merissa

AU - Unadkat, Jignesh

AU - Feili-Hariri, Maryam

PY - 2008/6

Y1 - 2008/6

N2 - We investigated the effect of autologous mesenchymal stem cells (MSC) on multiple unmodified donor bone marrow (BM) infusions and vascularized skin graft outcome. BM-derived rat MSC were examined for phenotype and function. MSC/MSC-conditioned-medium suppressed IFN-γ production by T cells and modified DC function. Infusions of MSC with one-time BM improved vascularized skin graft survival, while with one-two-times BM reversed graft versus host disease (GVHD). Mixed chimerism was enhanced in recipients given two-four-times BM with MSC infusions. Interestingly, four-times BM infusions with MSC delayed GVHD onset, reduced host tissue damage and enhanced vascularized skin allograft survival compared to four-times BM alone. These data demonstrate that, the co-infusion of MSC with unmodified BM limit the toxicity of allogeneic BM transplantation, enhance mixed chimerism and improve vascularized skin graft survival. These findings provide insights for the development of autologous MSC-based BM transplantation and prevention of graft rejection or treatment of autoimmunity.

AB - We investigated the effect of autologous mesenchymal stem cells (MSC) on multiple unmodified donor bone marrow (BM) infusions and vascularized skin graft outcome. BM-derived rat MSC were examined for phenotype and function. MSC/MSC-conditioned-medium suppressed IFN-γ production by T cells and modified DC function. Infusions of MSC with one-time BM improved vascularized skin graft survival, while with one-two-times BM reversed graft versus host disease (GVHD). Mixed chimerism was enhanced in recipients given two-four-times BM with MSC infusions. Interestingly, four-times BM infusions with MSC delayed GVHD onset, reduced host tissue damage and enhanced vascularized skin allograft survival compared to four-times BM alone. These data demonstrate that, the co-infusion of MSC with unmodified BM limit the toxicity of allogeneic BM transplantation, enhance mixed chimerism and improve vascularized skin graft survival. These findings provide insights for the development of autologous MSC-based BM transplantation and prevention of graft rejection or treatment of autoimmunity.

KW - Bone marrow

KW - GVHD

KW - Mesenchymal stem cells

KW - Rat

KW - Vascularized skin

UR - http://www.scopus.com/inward/record.url?scp=45249100402&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45249100402&partnerID=8YFLogxK

U2 - 10.1016/j.clim.2008.02.003

DO - 10.1016/j.clim.2008.02.003

M3 - Article

VL - 127

SP - 348

EP - 358

JO - Clinical Immunology

JF - Clinical Immunology

SN - 1521-6616

IS - 3

ER -