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Cell & Gene Therapy Insights

Cell & Gene Therapy Insights

Dendritic cells as effectors of mesenchymal stem cell therapy in lupus patients

A research study has uncovered the critical orchestrators of allogeneic UC-MSCs-mediated immunoregulation in systemic lupus erythematosus patients.

Mesenchymal stem cell (MSC) therapy has been used in the clinic for many diseases, however, the underlying therapeutic mechanism of its action has not been understood fully.

In the present study published in Nature Communications, Dr Lingyun Sun and team at Nanjing University Medical School (China) investigated the therapeutic mechanism through which umbilical cord (UC)-derived MSCs exhibited immunoregulatory function in systemic lupus erythematosus (SLE), an autoimmune disease characterized by activation of B and T lymphocytes.

The study showed that the number of peripheral tolerogenic dendritic cells CD1c+DCs, a subclass of DCs, and the levels of serum FLT3L were significantly decreased in SLE patients compared with healthy controls. Transplanting allogeneic UC-MSCs upregulated peripheral blood dendritic cells and serum FLT3L, implying that these could be two of the effectors through which MSCs exert their positive effect in lupus patients.

FLT3L on UC-MSCs bind to FLT3 on dendritic cells to promote proliferation and inhibit its apoptosis. Interestingly, by reducing FLT3L on MSCs with small interfering RNA abolished the upregulation of tolerogenic dendritic cells in lupus patients treated with MSCs.

In conclusion, the present study showed that UC-MSCs activated tolerogenic dendritic cells which in turn suppressed inflammation in lupus patients. These findings are crucial for MSC therapeutic applications in SLE.

Source: Mesenchymal stem cell therapy induces FLT3L and CD1c+ dendritic cells in systemic lupus erythematosus patients. Yuan X et al., Nature Communications, June 2019. DOI

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