LBP03: ALLOGENEIC-DRIVEN BENEFIT OF HUMAN CARDIAC-DERIVED STEM/PROGENITOR CELLS

Abstract

Aim Today, using human cardiac-derived stem/progenitor cells (hCPC) to repair injured inflamed myocardium is beyond cell stemness-related biologics, and involves paracrine effect as important therapeutic element in addition to regenerative one. Autologous hCPC were proving not to be optimum. This enhanced the prospects of using allogeneic cells although allogenicity is a striking system that can produce detrimental and beneficial effects. We aimed at defining whether allogeneic setting of hCPC within the context of cardiac repair is detrimental or beneficial. Methods Using an experimental model of allogeneic stimulation we investigated hCPC crosstalk with adaptive and innate immune effector cells and their reactivity with allo-HLA antibodies. Results Whether under inflammatory conditions or not, interactions of hCPC with major composites of the adaptive and innate immune system, T and natural killer cells, respectively, in allogeneic setting trigger and expand regulatory anti-inflammatory rather than inflammatory/deleterious immune response. The HLA molecules but also immune-regulatory molecule PD-L1 orchestrate this “tolerogenic/immunomodulatory” behavior. In regard of humoral antibody-mediated immunity, hCPC can variably react with allo-HLA antibodies present in serum depending on their HLA expression level. hCPC reactivity with anti-HLA resulted in low complement-dependent cytotoxicity and negligible antibody-dependent cell-mediated cytotoxicity thus, minimal deleterious effect. In contrast, we found that engagement of HLA class I or II molecules on hCPC by respective specific antibodies induces rapid phosphorylation of a major pathway of cells proliferation and survival, MAPK/Erk. Although warrant further investigation, this suggests that allo-HLA antibodies could enhance engraftment, proliferation, and survival of hCPC and potentially contribute to myocardium repair. Conclusions Collectively, our data indicate that allogenicity of hCPC within cardiac repair context is beneficial rather than detrimental. It promotes the immune response toward regeneration/reparation and suggests allogeneic hCPC crosstalk with composites of immune system as an eventual “paracrine” therapeutic element.