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Immunogenicity of allogeneic mesenchymal stem cells.

Schu S, Nosov M, O'Flynn L, Shaw G, Treacy O, Barry F, Murphy M, O'Brien T, Ritter T - J. Cell. Mol. Med. (2012)

Bottom Line: However, intravenous injection of allo-MSCs in rats led to the formation of alloantibodies with the capacity to facilitate complement-mediated lysis, although IgM levels were markedly decreased compared with animals that received T cells.The allo-MSC induced immune response was sufficient to lead to significantly reduced survival of subsequently injected allo-MSCs.Interestingly, no increased immunogenicity of IFN-γ stimulated allo-MSCs was observed in vivo.

View Article: PubMed Central - PubMed

Affiliation: College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.

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Allogeneic mesenchymal stem cells (MSCs) do not induce markers of T cell activation. LEW rats were injected with 5 × 106 DA MSCs, DA T cells or PBS. Spleens were harvested 24 or 48 hr after injection and expression of early activation markers was analysed. Cells were stained with anti-CD4, anti-CD25, and anti-CD71 (left) or anti-CD4 and anti-CD62L (right), or appropriate isotype controls. Shown are mean percentages of positive cells ± S.D. (n = 2–3).
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fig03: Allogeneic mesenchymal stem cells (MSCs) do not induce markers of T cell activation. LEW rats were injected with 5 × 106 DA MSCs, DA T cells or PBS. Spleens were harvested 24 or 48 hr after injection and expression of early activation markers was analysed. Cells were stained with anti-CD4, anti-CD25, and anti-CD71 (left) or anti-CD4 and anti-CD62L (right), or appropriate isotype controls. Shown are mean percentages of positive cells ± S.D. (n = 2–3).

Mentions: Next, we analysed whether injection of allogeneic MSCs leads to the activation of T cells in vivo. First, we tested for systemic early activation of CD4+ T cells in response to allogeneic MSCs. Spleens were harvested from animals 24 or 48 hr after injection of 5 × 106 MSCs, T cells or PBS and expression of the early activation markers CD25 and CD71 as well as expression of CD62L on CD4+ T cells was analysed by flow cytometry (Fig. 3). We found that in allo-T cell-injected animals, more CD4+CD25+CD71+ and CD4+CD62L− cells were detectable at 24 and 48 hr compared to PBS and allo-MSC-injected rats. Levels of T cell activation were similar in allo-MSC-treated and control-treated rats at both time points. In addition to the characterization of T cell activation in the spleen, T cells from mesenteric lymph nodes were also analysed for the expression of pro-inflammatory cytokines upon injection of allo-MSCs. The relative quantities of IL-1β, IL-2, IL-6 and IFN-γ mRNAs compared with β-actin mRNA were analysed with TaqMan semi-quantitative real time PCR (Invitrogen). No significant changes in the mRNA expression profile of any of these immune markers could be detected in lymphocytes of allo-MSC-injected animals after 24 and 48 hr when compared to PBS controls (Fig. S1). In contrast, injection of allogeneic T cells led to a transient upregulation of mRNAs of all inflammatory cytokines investigated after 24 hr.


Immunogenicity of allogeneic mesenchymal stem cells.

Schu S, Nosov M, O'Flynn L, Shaw G, Treacy O, Barry F, Murphy M, O'Brien T, Ritter T - J. Cell. Mol. Med. (2012)

Allogeneic mesenchymal stem cells (MSCs) do not induce markers of T cell activation. LEW rats were injected with 5 × 106 DA MSCs, DA T cells or PBS. Spleens were harvested 24 or 48 hr after injection and expression of early activation markers was analysed. Cells were stained with anti-CD4, anti-CD25, and anti-CD71 (left) or anti-CD4 and anti-CD62L (right), or appropriate isotype controls. Shown are mean percentages of positive cells ± S.D. (n = 2–3).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3822979&req=5

fig03: Allogeneic mesenchymal stem cells (MSCs) do not induce markers of T cell activation. LEW rats were injected with 5 × 106 DA MSCs, DA T cells or PBS. Spleens were harvested 24 or 48 hr after injection and expression of early activation markers was analysed. Cells were stained with anti-CD4, anti-CD25, and anti-CD71 (left) or anti-CD4 and anti-CD62L (right), or appropriate isotype controls. Shown are mean percentages of positive cells ± S.D. (n = 2–3).
Mentions: Next, we analysed whether injection of allogeneic MSCs leads to the activation of T cells in vivo. First, we tested for systemic early activation of CD4+ T cells in response to allogeneic MSCs. Spleens were harvested from animals 24 or 48 hr after injection of 5 × 106 MSCs, T cells or PBS and expression of the early activation markers CD25 and CD71 as well as expression of CD62L on CD4+ T cells was analysed by flow cytometry (Fig. 3). We found that in allo-T cell-injected animals, more CD4+CD25+CD71+ and CD4+CD62L− cells were detectable at 24 and 48 hr compared to PBS and allo-MSC-injected rats. Levels of T cell activation were similar in allo-MSC-treated and control-treated rats at both time points. In addition to the characterization of T cell activation in the spleen, T cells from mesenteric lymph nodes were also analysed for the expression of pro-inflammatory cytokines upon injection of allo-MSCs. The relative quantities of IL-1β, IL-2, IL-6 and IFN-γ mRNAs compared with β-actin mRNA were analysed with TaqMan semi-quantitative real time PCR (Invitrogen). No significant changes in the mRNA expression profile of any of these immune markers could be detected in lymphocytes of allo-MSC-injected animals after 24 and 48 hr when compared to PBS controls (Fig. S1). In contrast, injection of allogeneic T cells led to a transient upregulation of mRNAs of all inflammatory cytokines investigated after 24 hr.

Bottom Line: However, intravenous injection of allo-MSCs in rats led to the formation of alloantibodies with the capacity to facilitate complement-mediated lysis, although IgM levels were markedly decreased compared with animals that received T cells.The allo-MSC induced immune response was sufficient to lead to significantly reduced survival of subsequently injected allo-MSCs.Interestingly, no increased immunogenicity of IFN-γ stimulated allo-MSCs was observed in vivo.

View Article: PubMed Central - PubMed

Affiliation: College of Medicine, Nursing and Health Sciences, School of Medicine, Regenerative Medicine Institute, National University of Ireland, Galway, Ireland.

Show MeSH
Related in: MedlinePlus