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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.


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Effector T cells are suppressed by multipotent adult progenitor cell (MAPC)-conditioned medium in a dose-dependent manner in RA and HD. MAPCs were grown in serum-free MAPC medium that contains tumor necrosis factor-α (10 ng/ml), interleukin-1β (10 ng/ml), and an equivalent amount of interferon (IFN) γ. After 3 days IFNγ was immunodepleted. Control growth medium was used as a control for CCM; it is the initial medium but has not been exposed to MAPCs. CCM concentrations between 12.5% and 87.5% of the total medium were tested. Suppression was observed at CCM concentrations of greater than 50% by volume. Abbreviations: CCM, multipotent adult progenitor cell-conditioned medium; HD1–HD3, blood from healthy donors specific to this experiment; RA1–RA4, distinct rheumatoid arthritis patients specific to this experiment.
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Figure 2: Effector T cells are suppressed by multipotent adult progenitor cell (MAPC)-conditioned medium in a dose-dependent manner in RA and HD. MAPCs were grown in serum-free MAPC medium that contains tumor necrosis factor-α (10 ng/ml), interleukin-1β (10 ng/ml), and an equivalent amount of interferon (IFN) γ. After 3 days IFNγ was immunodepleted. Control growth medium was used as a control for CCM; it is the initial medium but has not been exposed to MAPCs. CCM concentrations between 12.5% and 87.5% of the total medium were tested. Suppression was observed at CCM concentrations of greater than 50% by volume. Abbreviations: CCM, multipotent adult progenitor cell-conditioned medium; HD1–HD3, blood from healthy donors specific to this experiment; RA1–RA4, distinct rheumatoid arthritis patients specific to this experiment.

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
Effector T cells are suppressed by multipotent adult progenitor cell (MAPC)-conditioned medium in a dose-dependent manner in RA and HD. MAPCs were grown in serum-free MAPC medium that contains tumor necrosis factor-α (10 ng/ml), interleukin-1β (10 ng/ml), and an equivalent amount of interferon (IFN) γ. After 3 days IFNγ was immunodepleted. Control growth medium was used as a control for CCM; it is the initial medium but has not been exposed to MAPCs. CCM concentrations between 12.5% and 87.5% of the total medium were tested. Suppression was observed at CCM concentrations of greater than 50% by volume. Abbreviations: CCM, multipotent adult progenitor cell-conditioned medium; HD1–HD3, blood from healthy donors specific to this experiment; RA1–RA4, distinct rheumatoid arthritis patients specific to this experiment.
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Related In: Results  -  Collection

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Figure 2: Effector T cells are suppressed by multipotent adult progenitor cell (MAPC)-conditioned medium in a dose-dependent manner in RA and HD. MAPCs were grown in serum-free MAPC medium that contains tumor necrosis factor-α (10 ng/ml), interleukin-1β (10 ng/ml), and an equivalent amount of interferon (IFN) γ. After 3 days IFNγ was immunodepleted. Control growth medium was used as a control for CCM; it is the initial medium but has not been exposed to MAPCs. CCM concentrations between 12.5% and 87.5% of the total medium were tested. Suppression was observed at CCM concentrations of greater than 50% by volume. Abbreviations: CCM, multipotent adult progenitor cell-conditioned medium; HD1–HD3, blood from healthy donors specific to this experiment; RA1–RA4, distinct rheumatoid arthritis patients specific to this experiment.
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