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Development of a Functional Biomarker for Use in Cell-Based Therapy Studies in Seropositive Rheumatoid Arthritis

View Article: PubMed Central - PubMed

ABSTRACT

This study tested the hypothesis that an ex vivo T-cell suppression assay could estimate response to novel cell-based therapy for rheumatoid arthritis (RA). Results showed multipotent adult progenitor cell products suppressed RA effector T cells. The study demonstrated the feasibility of using suppressor assays to detect biological effects of cell-based therapy in RA and suggests these effects are dose-dependent.

No MeSH data available.


Related in: MedlinePlus

Multipotent adult progenitor cells (MAPCs) suppressed active RA and HD effector T-cell (Teff) response. CD4+ cells were isolated from peripheral blood mononuclear cells from HD and patients with RA. Cells were stained and then sorted into Teff and Treg populations based on CD4 and CD25 expression. Teffs were stimulated with anti-CD2/CD3/CD28-coated beads and then loaded with eFluor670 vital dye. Teff proliferation was measured using flow cytometry. (A): T-cell suppression assays were performed in the presence of BCM with or without Tregs at ratios of 1:1 and 1:2. (B): T-cell suppression assays were performed with CCM or GMC. Abbreviations: BCM, basal medium; CCM, multipotent adult progenitor cell-conditioned medium; GMC, control growth medium; HD, blood from healthy donors; RA, rheumatoid arthritis patient; Treg, T-regulatory cell.
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Figure 1: Multipotent adult progenitor cells (MAPCs) suppressed active RA and HD effector T-cell (Teff) response. CD4+ cells were isolated from peripheral blood mononuclear cells from HD and patients with RA. Cells were stained and then sorted into Teff and Treg populations based on CD4 and CD25 expression. Teffs were stimulated with anti-CD2/CD3/CD28-coated beads and then loaded with eFluor670 vital dye. Teff proliferation was measured using flow cytometry. (A): T-cell suppression assays were performed in the presence of BCM with or without Tregs at ratios of 1:1 and 1:2. (B): T-cell suppression assays were performed with CCM or GMC. Abbreviations: BCM, basal medium; CCM, multipotent adult progenitor cell-conditioned medium; GMC, control growth medium; HD, blood from healthy donors; RA, rheumatoid arthritis patient; Treg, T-regulatory cell.

Mentions: To characterize the effects of MAPC products on Teff proliferation or suppression, Teffs were stimulated using anti-CD2, -3, and -28 antibody beads. Teff from HD and RA proliferated and were suppressed by Tregs (Fig. 1A). HD and RA Teffs were both suppressed when cultured in CCM (Fig. 1B). Proliferation rates that dropped to 7% for HD and 10% for RA were observed in the presence of CCM. This correlated with 87% suppression of Teff proliferation in HD and 78% suppression in RA. Because might be anticipated for a drug, the effects of CCM on Teffs were dose dependent with concentrations from 12.5% to 87.5% of CCM tested. The greatest effects of CCM were observed at concentrations of CCM greater than 50% by volume (Fig. 2).


Development of a Functional Biomarker for Use in Cell-Based Therapy Studies in Seropositive Rheumatoid Arthritis
Multipotent adult progenitor cells (MAPCs) suppressed active RA and HD effector T-cell (Teff) response. CD4+ cells were isolated from peripheral blood mononuclear cells from HD and patients with RA. Cells were stained and then sorted into Teff and Treg populations based on CD4 and CD25 expression. Teffs were stimulated with anti-CD2/CD3/CD28-coated beads and then loaded with eFluor670 vital dye. Teff proliferation was measured using flow cytometry. (A): T-cell suppression assays were performed in the presence of BCM with or without Tregs at ratios of 1:1 and 1:2. (B): T-cell suppression assays were performed with CCM or GMC. Abbreviations: BCM, basal medium; CCM, multipotent adult progenitor cell-conditioned medium; GMC, control growth medium; HD, blood from healthy donors; RA, rheumatoid arthritis patient; Treg, T-regulatory cell.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4835254&req=5

Figure 1: Multipotent adult progenitor cells (MAPCs) suppressed active RA and HD effector T-cell (Teff) response. CD4+ cells were isolated from peripheral blood mononuclear cells from HD and patients with RA. Cells were stained and then sorted into Teff and Treg populations based on CD4 and CD25 expression. Teffs were stimulated with anti-CD2/CD3/CD28-coated beads and then loaded with eFluor670 vital dye. Teff proliferation was measured using flow cytometry. (A): T-cell suppression assays were performed in the presence of BCM with or without Tregs at ratios of 1:1 and 1:2. (B): T-cell suppression assays were performed with CCM or GMC. Abbreviations: BCM, basal medium; CCM, multipotent adult progenitor cell-conditioned medium; GMC, control growth medium; HD, blood from healthy donors; RA, rheumatoid arthritis patient; Treg, T-regulatory cell.
Mentions: To characterize the effects of MAPC products on Teff proliferation or suppression, Teffs were stimulated using anti-CD2, -3, and -28 antibody beads. Teff from HD and RA proliferated and were suppressed by Tregs (Fig. 1A). HD and RA Teffs were both suppressed when cultured in CCM (Fig. 1B). Proliferation rates that dropped to 7% for HD and 10% for RA were observed in the presence of CCM. This correlated with 87% suppression of Teff proliferation in HD and 78% suppression in RA. Because might be anticipated for a drug, the effects of CCM on Teffs were dose dependent with concentrations from 12.5% to 87.5% of CCM tested. The greatest effects of CCM were observed at concentrations of CCM greater than 50% by volume (Fig. 2).

View Article: PubMed Central - PubMed

ABSTRACT

This study tested the hypothesis that an ex vivo T-cell suppression assay could estimate response to novel cell-based therapy for rheumatoid arthritis (RA). Results showed multipotent adult progenitor cell products suppressed RA effector T cells. The study demonstrated the feasibility of using suppressor assays to detect biological effects of cell-based therapy in RA and suggests these effects are dose-dependent.

No MeSH data available.


Related in: MedlinePlus