Allogeneic ADSCs induce CD8 T cell-mediated cytotoxicity and faster cell death after exposure to xenogeneic serum or proinflammatory cytokines.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

This study examined the induction of recipient T-cell cytotoxicity after exposure to allogeneic adipose-derived mesenchymal stem cells (ADSCs). ADSCs pre-exposed to xenogeneic serum significantly induced cytotoxicity through CD8 T-cell granzyme B secretion after allogeneic antigen stimulation, and this effect was increased with prolonged reaction time. ADSCs pretreated with proinflammatory cytokines also induced cytotoxicity through granzyme B secretion and significantly increased human leukocyte antigen (HLA)-ABC expression. T-cell cytotoxicity towards ADSCs grown in xeno-free medium (XF-ADSCs) was lower than that towards ADSCs exposed to xenogeneic serum or proinflammatory cytokines, but XF-ADSCs still induced cytotoxicity. We further investigated the causes of T-cell cytotoxicity towards XF-ADSCs. XF-ADSC death was effectively inhibited by HLA-blocking antibodies, suggesting that ADSC HLAs are a major cause of alloreactive T-cell generation. These results indicated that culturing of allogeneic ADSCs with recipient serum may alleviate alloreactive CD8 T-cell cytotoxicity. Ultimately, development of therapeutic agents using autologous ADSCs would be a suitable way to avoid immunogenicity and CD8 T cell-mediated cytotoxicity, but more attention should be paid to the potential immunogenicity of allogeneic ADSCs, which could perhaps be mitigated through the use of immunosuppressa

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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