Kidney-derived mesenchymal stromal cells modulate dendritic cell function to suppress alloimmune responses and delay allograft rejection

Yanfei Huang, Ping Chen, Cassie B. Zhang, Gang Jee Ko, Miriam Ruiz, Paolo Fiorina, Mehboob A. Hussain, Barbara A. Wasowska, Hamid Rabb, Karl L. Womer

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background. Mesenchymal stromal cells (MSCs) are multipotent cells with immunoregulatory capacity that are present in most adult organs. We previously demonstrated that co-culture of C57BL/6 kidney-derived MSCs (KSCs) in syngeneic bone marrow-derived dendritic cell (DC) culture induced a DC phenotype (KSC-DC) with reduced major histocompatibility complex (MHC) class II/increased CD80 expression and ability to suppress T-cell responses. Methods. To study their effects on allogeneic DCs, C57BL/6 KSCs were added to incipient BALB/c DC culture, with surface expression of MHC class II/CD80 measured by fluorescence-activated cell sorting. The ability to stimulate T-cell responses was then assessed in an allogeneic mixed leukocyte response. Next, we isolated either BALB/c (donor) or C57BL/6 (recipient) KSC-DCs from co-culture and measured the tempo of rejection after cotransplantation with islet grafts in a mouse model of islet transplantation. Finally, we measured the effects of KSC-DC stimulation on B-cell proliferation and IgM/IgG production in allogeneic cultures. Results. C57BL/6 KSCs induced a BALB/c DC phenotype with significantly decreased MHC class II, increased CD80 expression, and decreased T-cell stimulatory capacity in the mixed leukocyte response (P<0.01 vs. control). Cotransplantation of donor (BALB/c) but not recipient (C57BL/6) KSC-DCs resulted in significant delay of rejection after islet transplantation (P<0.01 vs. control). Finally, stimulation by KSC-DCs resulted in significantly reduced B-cell proliferation and antibody production in allogeneic culture (P<0.01 vs. control). Conclusions. Our results highlight an important mechanism of MSC-based immunotherapy and its potential for use in clinical transplantation as prevention of rejection and possibly sensitization.

Original languageEnglish
Pages (from-to)1307-1311
Number of pages5
JournalTransplantation
Volume90
Issue number12
DOIs
Publication statusPublished - 2010 Dec 27

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Mesenchymal Stromal Cells
Dendritic Cells
Allografts
Kidney
Major Histocompatibility Complex
Islets of Langerhans Transplantation
Coculture Techniques
T-Lymphocytes
Leukocytes
B-Lymphocytes
Cell Culture Techniques
Cell Proliferation
Phenotype
Immunotherapy
Antibody Formation
Immunoglobulin M
Flow Cytometry
Immunoglobulin G
Transplantation
Bone Marrow

Keywords

  • Antigen-presenting cells
  • Dendritic cells
  • Islet transplantation
  • Mesenchymal stem cells

ASJC Scopus subject areas

  • Transplantation

Cite this

Kidney-derived mesenchymal stromal cells modulate dendritic cell function to suppress alloimmune responses and delay allograft rejection. / Huang, Yanfei; Chen, Ping; Zhang, Cassie B.; Ko, Gang Jee; Ruiz, Miriam; Fiorina, Paolo; Hussain, Mehboob A.; Wasowska, Barbara A.; Rabb, Hamid; Womer, Karl L.

In: Transplantation, Vol. 90, No. 12, 27.12.2010, p. 1307-1311.

Research output: Contribution to journalArticle

Huang, Y, Chen, P, Zhang, CB, Ko, GJ, Ruiz, M, Fiorina, P, Hussain, MA, Wasowska, BA, Rabb, H & Womer, KL 2010, 'Kidney-derived mesenchymal stromal cells modulate dendritic cell function to suppress alloimmune responses and delay allograft rejection', Transplantation, vol. 90, no. 12, pp. 1307-1311. https://doi.org/10.1097/TP.0b013e3181fdd9eb
Huang, Yanfei ; Chen, Ping ; Zhang, Cassie B. ; Ko, Gang Jee ; Ruiz, Miriam ; Fiorina, Paolo ; Hussain, Mehboob A. ; Wasowska, Barbara A. ; Rabb, Hamid ; Womer, Karl L. / Kidney-derived mesenchymal stromal cells modulate dendritic cell function to suppress alloimmune responses and delay allograft rejection. In: Transplantation. 2010 ; Vol. 90, No. 12. pp. 1307-1311.
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T1 - Kidney-derived mesenchymal stromal cells modulate dendritic cell function to suppress alloimmune responses and delay allograft rejection

AU - Huang, Yanfei

AU - Chen, Ping

AU - Zhang, Cassie B.

AU - Ko, Gang Jee

AU - Ruiz, Miriam

AU - Fiorina, Paolo

AU - Hussain, Mehboob A.

AU - Wasowska, Barbara A.

AU - Rabb, Hamid

AU - Womer, Karl L.

PY - 2010/12/27

Y1 - 2010/12/27

N2 - Background. Mesenchymal stromal cells (MSCs) are multipotent cells with immunoregulatory capacity that are present in most adult organs. We previously demonstrated that co-culture of C57BL/6 kidney-derived MSCs (KSCs) in syngeneic bone marrow-derived dendritic cell (DC) culture induced a DC phenotype (KSC-DC) with reduced major histocompatibility complex (MHC) class II/increased CD80 expression and ability to suppress T-cell responses. Methods. To study their effects on allogeneic DCs, C57BL/6 KSCs were added to incipient BALB/c DC culture, with surface expression of MHC class II/CD80 measured by fluorescence-activated cell sorting. The ability to stimulate T-cell responses was then assessed in an allogeneic mixed leukocyte response. Next, we isolated either BALB/c (donor) or C57BL/6 (recipient) KSC-DCs from co-culture and measured the tempo of rejection after cotransplantation with islet grafts in a mouse model of islet transplantation. Finally, we measured the effects of KSC-DC stimulation on B-cell proliferation and IgM/IgG production in allogeneic cultures. Results. C57BL/6 KSCs induced a BALB/c DC phenotype with significantly decreased MHC class II, increased CD80 expression, and decreased T-cell stimulatory capacity in the mixed leukocyte response (P<0.01 vs. control). Cotransplantation of donor (BALB/c) but not recipient (C57BL/6) KSC-DCs resulted in significant delay of rejection after islet transplantation (P<0.01 vs. control). Finally, stimulation by KSC-DCs resulted in significantly reduced B-cell proliferation and antibody production in allogeneic culture (P<0.01 vs. control). Conclusions. Our results highlight an important mechanism of MSC-based immunotherapy and its potential for use in clinical transplantation as prevention of rejection and possibly sensitization.

AB - Background. Mesenchymal stromal cells (MSCs) are multipotent cells with immunoregulatory capacity that are present in most adult organs. We previously demonstrated that co-culture of C57BL/6 kidney-derived MSCs (KSCs) in syngeneic bone marrow-derived dendritic cell (DC) culture induced a DC phenotype (KSC-DC) with reduced major histocompatibility complex (MHC) class II/increased CD80 expression and ability to suppress T-cell responses. Methods. To study their effects on allogeneic DCs, C57BL/6 KSCs were added to incipient BALB/c DC culture, with surface expression of MHC class II/CD80 measured by fluorescence-activated cell sorting. The ability to stimulate T-cell responses was then assessed in an allogeneic mixed leukocyte response. Next, we isolated either BALB/c (donor) or C57BL/6 (recipient) KSC-DCs from co-culture and measured the tempo of rejection after cotransplantation with islet grafts in a mouse model of islet transplantation. Finally, we measured the effects of KSC-DC stimulation on B-cell proliferation and IgM/IgG production in allogeneic cultures. Results. C57BL/6 KSCs induced a BALB/c DC phenotype with significantly decreased MHC class II, increased CD80 expression, and decreased T-cell stimulatory capacity in the mixed leukocyte response (P<0.01 vs. control). Cotransplantation of donor (BALB/c) but not recipient (C57BL/6) KSC-DCs resulted in significant delay of rejection after islet transplantation (P<0.01 vs. control). Finally, stimulation by KSC-DCs resulted in significantly reduced B-cell proliferation and antibody production in allogeneic culture (P<0.01 vs. control). Conclusions. Our results highlight an important mechanism of MSC-based immunotherapy and its potential for use in clinical transplantation as prevention of rejection and possibly sensitization.

KW - Antigen-presenting cells

KW - Dendritic cells

KW - Islet transplantation

KW - Mesenchymal stem cells

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