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LP-083 Phorbol ester activates human mesenchymal stem cells to inhibit B cells and ameliorate lupus symptoms in MRL.Faslpr mice
  1. Hong Kyung Lee1,2 and
  2. Sang-Bae Han1
  1. 1College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28160, Republic of Korea
  2. 2Bioengineering Institute, Corestem Inc., Gyeonggi 13486, Republic of Korea


Description Rationale: Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production by hyper-activated B cells. Although mesenchymal stem cells (MSCs) ameliorate lupus symptoms by inhibiting T cells, whether they inhibit B cells has been controversial. Here we address this issue and reveal how to prime MSCs to inhibit B cells and improve the efficacy of MSCs in SLE.

Methods We examined the effect of MSCs on purified B cells in vitro and the therapeutic efficacy of MSCs in lupus-prone MRL.Faslpr mice. We screened chemicals for their ability to activate MSCs to inhibit B cells.

Results Mouse bone marrow-derived MSCs inhibited mouse B cells in a CXCL12-dependent manner, whereas human bone marrow-derived MSCs (hMSCs) did not inhibit human B (hB) cells. We used a chemical approach to overcome this hurdle and found that phorbol myristate acetate (PMA), phorbol 12,13-dibutyrate, and ingenol-3-angelate rendered hMSCs capable of inhibiting IgM production by hB cells. As to the mechanism, PMA-primed hMSCs attracted hB cells in a CXCL10-dependent manner and induced hB cell apoptosis in a PD-L1-dependent manner. Finally, we showed that PMA-primed hMSCs were better than naïve hMSCs at ameliorating SLE progression in MRL.Faslpr mice.

Conclusions Conclusion: Taken together, our data demonstrate that phorbol esters might be good tool compounds to activate MSCs to inhibit B cells and suggest that our chemical approach might allow to improve the therapeutic efficacy of hMSCs in SLE.

  • B cell
  • mesenchymal stem cell
  • phorbol ester

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