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Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells.

Joo S, Lim HJ, Jackson JD, Atala A, Yoo JJ - J Tissue Eng (2014)

Bottom Line: Therefore, our aim was to evaluate the effects of mesenchymal stem cell differentiation on the immune characteristics of cells in vitro.Two different 5-aza-2'-deoxycytidine doses (0.5 and 3 µM) were evaluated for their effects on mesenchymal stem cell skeletal myogenic differentiation potential, immune antigen expression, and mixed lymphocytic reactions.Myogenic-induced mesenchymal stem cells do not elicit alloreactive lymphocyte proliferative responses and are able to modulate immune responses.

View Article: PubMed Central - PubMed

Affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA ; Biomedical Research Institute, Joint Institute for Regenerative Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.

ABSTRACT
Cell therapy for patients who have intractable muscle disorders may require highly regenerative cells from young, healthy allogeneic donors. Mesenchymal stem cells are currently under clinical investigation because they are known to induce muscle regeneration and believed to be immune privileged, thus making them suitable for allogeneic applications. However, it is unclear whether allogeneic and myogenic-induced mesenchymal stem cells retain their immunomodulatory characteristics. Therefore, our aim was to evaluate the effects of mesenchymal stem cell differentiation on the immune characteristics of cells in vitro. We investigated the immunologic properties of mesenchymal stem cells after myogenic induction. Mesenchymal stem cells were obtained from C57BL/6 mice and the C3H/10T1/2 murine mesenchymal stem cell line. Two different 5-aza-2'-deoxycytidine doses (0.5 and 3 µM) were evaluated for their effects on mesenchymal stem cell skeletal myogenic differentiation potential, immune antigen expression, and mixed lymphocytic reactions. Using a mixed lymphocytic reaction, we determined the optimal splenocyte proliferation inhibition dose. The induction of regulatory T cells was markedly increased by the addition of 3 µM 5-aza-2'-deoxycytidine-treated mesenchymal stem cells. Myogenic-induced mesenchymal stem cells do not elicit alloreactive lymphocyte proliferative responses and are able to modulate immune responses. These findings support the hypothesis that myogenic-induced mesenchymal stem cells may be transplantable across allogeneic barriers.

No MeSH data available.


Related in: MedlinePlus

Induction of regulatory T cells in response to undifferentiated and 5-aza-CdR-treated MSCs. (a–c) After 5 days of coculture, splenocytes cocultured with MSCs were stained with antibodies against CD4, CD25, and Foxp3 and assessed by flow cytometry. Addition of undifferentiated MSCs and 5-aza-CdR-treated myogenic-induced MSCs dose dependently increased the proportion of (a) CD4+Foxp3+, (b) CD4+CD25+, and (c) CD25+Foxp3+ expression in splenocyte culture by flow cytometry. Numbers represent percentages of cells staining positive for the given antibody. Data are representative of two independent experiments with the same pattern of results.5-Aza-CdR: 5-aza-2′-deoxycytidine; MSC: mesenchymal stem cell; PE: phycoerythrin; FITC: fluorescence isothiocyanate; APC: allophycocyanin.
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fig4-2041731414524758: Induction of regulatory T cells in response to undifferentiated and 5-aza-CdR-treated MSCs. (a–c) After 5 days of coculture, splenocytes cocultured with MSCs were stained with antibodies against CD4, CD25, and Foxp3 and assessed by flow cytometry. Addition of undifferentiated MSCs and 5-aza-CdR-treated myogenic-induced MSCs dose dependently increased the proportion of (a) CD4+Foxp3+, (b) CD4+CD25+, and (c) CD25+Foxp3+ expression in splenocyte culture by flow cytometry. Numbers represent percentages of cells staining positive for the given antibody. Data are representative of two independent experiments with the same pattern of results.5-Aza-CdR: 5-aza-2′-deoxycytidine; MSC: mesenchymal stem cell; PE: phycoerythrin; FITC: fluorescence isothiocyanate; APC: allophycocyanin.

Mentions: In order to assess the immunoregulatory function of MSCs related to Treg cells, we designed a transwell assay using the splenocytes from C57BL/6 mice in the presence of various concentrations of undifferentiated and 5-aza-CdR-treated myogenic-induced MSCs. Treg cells were increased with an increase in MSC dose from 104 to 106. Addition of undifferentiated MSCs and 5-aza-CdR-treated myogenic-induced MSCs dose dependently increased the proportion of CD4+Foxp3+ (Figure 4(a)), CD4+CD25+ (Figure 4(b)), and CD25+Foxp3+ (Figure 4(c)) expression in splenocyte culture by flow cytometry. In the presence of 3 µM 5-aza-CdR-treated MSCs, the proportion of CD4+Foxp3+, CD4+CD25+, and CD25+Foxp3+ expression in splenocytes showed highest.


Myogenic-induced mesenchymal stem cells are capable of modulating the immune response by regulatory T cells.

Joo S, Lim HJ, Jackson JD, Atala A, Yoo JJ - J Tissue Eng (2014)

Induction of regulatory T cells in response to undifferentiated and 5-aza-CdR-treated MSCs. (a–c) After 5 days of coculture, splenocytes cocultured with MSCs were stained with antibodies against CD4, CD25, and Foxp3 and assessed by flow cytometry. Addition of undifferentiated MSCs and 5-aza-CdR-treated myogenic-induced MSCs dose dependently increased the proportion of (a) CD4+Foxp3+, (b) CD4+CD25+, and (c) CD25+Foxp3+ expression in splenocyte culture by flow cytometry. Numbers represent percentages of cells staining positive for the given antibody. Data are representative of two independent experiments with the same pattern of results.5-Aza-CdR: 5-aza-2′-deoxycytidine; MSC: mesenchymal stem cell; PE: phycoerythrin; FITC: fluorescence isothiocyanate; APC: allophycocyanin.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC3927963&req=5

fig4-2041731414524758: Induction of regulatory T cells in response to undifferentiated and 5-aza-CdR-treated MSCs. (a–c) After 5 days of coculture, splenocytes cocultured with MSCs were stained with antibodies against CD4, CD25, and Foxp3 and assessed by flow cytometry. Addition of undifferentiated MSCs and 5-aza-CdR-treated myogenic-induced MSCs dose dependently increased the proportion of (a) CD4+Foxp3+, (b) CD4+CD25+, and (c) CD25+Foxp3+ expression in splenocyte culture by flow cytometry. Numbers represent percentages of cells staining positive for the given antibody. Data are representative of two independent experiments with the same pattern of results.5-Aza-CdR: 5-aza-2′-deoxycytidine; MSC: mesenchymal stem cell; PE: phycoerythrin; FITC: fluorescence isothiocyanate; APC: allophycocyanin.
Mentions: In order to assess the immunoregulatory function of MSCs related to Treg cells, we designed a transwell assay using the splenocytes from C57BL/6 mice in the presence of various concentrations of undifferentiated and 5-aza-CdR-treated myogenic-induced MSCs. Treg cells were increased with an increase in MSC dose from 104 to 106. Addition of undifferentiated MSCs and 5-aza-CdR-treated myogenic-induced MSCs dose dependently increased the proportion of CD4+Foxp3+ (Figure 4(a)), CD4+CD25+ (Figure 4(b)), and CD25+Foxp3+ (Figure 4(c)) expression in splenocyte culture by flow cytometry. In the presence of 3 µM 5-aza-CdR-treated MSCs, the proportion of CD4+Foxp3+, CD4+CD25+, and CD25+Foxp3+ expression in splenocytes showed highest.

Bottom Line: Therefore, our aim was to evaluate the effects of mesenchymal stem cell differentiation on the immune characteristics of cells in vitro.Two different 5-aza-2'-deoxycytidine doses (0.5 and 3 µM) were evaluated for their effects on mesenchymal stem cell skeletal myogenic differentiation potential, immune antigen expression, and mixed lymphocytic reactions.Myogenic-induced mesenchymal stem cells do not elicit alloreactive lymphocyte proliferative responses and are able to modulate immune responses.

View Article: PubMed Central - PubMed

Affiliation: Wake Forest Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, NC, USA ; Biomedical Research Institute, Joint Institute for Regenerative Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea.

ABSTRACT
Cell therapy for patients who have intractable muscle disorders may require highly regenerative cells from young, healthy allogeneic donors. Mesenchymal stem cells are currently under clinical investigation because they are known to induce muscle regeneration and believed to be immune privileged, thus making them suitable for allogeneic applications. However, it is unclear whether allogeneic and myogenic-induced mesenchymal stem cells retain their immunomodulatory characteristics. Therefore, our aim was to evaluate the effects of mesenchymal stem cell differentiation on the immune characteristics of cells in vitro. We investigated the immunologic properties of mesenchymal stem cells after myogenic induction. Mesenchymal stem cells were obtained from C57BL/6 mice and the C3H/10T1/2 murine mesenchymal stem cell line. Two different 5-aza-2'-deoxycytidine doses (0.5 and 3 µM) were evaluated for their effects on mesenchymal stem cell skeletal myogenic differentiation potential, immune antigen expression, and mixed lymphocytic reactions. Using a mixed lymphocytic reaction, we determined the optimal splenocyte proliferation inhibition dose. The induction of regulatory T cells was markedly increased by the addition of 3 µM 5-aza-2'-deoxycytidine-treated mesenchymal stem cells. Myogenic-induced mesenchymal stem cells do not elicit alloreactive lymphocyte proliferative responses and are able to modulate immune responses. These findings support the hypothesis that myogenic-induced mesenchymal stem cells may be transplantable across allogeneic barriers.

No MeSH data available.


Related in: MedlinePlus