Abstract
The application of autologous endothelial progenitor cell (EPC) transplantation is a promising approach in therapeutic cardiovascular diseases and ischemic diseases. In this study, we compared the immunogenicity of EPCs, adipose tissue (AD)-derived mesenchymal stem cells (MSCs) and umbilical cord (UC)-derived MSCs by flow cytometry and the mixed lymphocyte reaction. The impact of AD-MSCs and UC-MSCs on the immunogenicity of EPCs was analyzed by the mixed lymphocyte reaction and cytokine secretion in vitro and was further tested by allogenic peripheral blood mononuclear cell (PBMC) induced immuno-rejection on a cell/matrigel graft in an SCID mouse model. EPCs and AD-MSCs express higher levels of MHC class I than UC-MSCs. All three kinds of cells are negative for MHC class II. UC-MSCs also express lower levels of IFN-γ receptor mRNA when compared with EPCs and AD-MSCs. EPCs can stimulate higher rates of proliferation of lymphocytes than AD-MSCs and UC-MSCs. Furthermore, AD-MSCs and UC-MSCs can modulate immune response and inhibit lymphocyte proliferation induced by EPCs, mainly through inhibition of the proliferation of CD8+ T cells. Compared with UC-MSCs, AD-MSCs can significantly improve vessel formation and maintain the integrity of neovascular structure in an EPC+MSC/matrigel graft in SCID mice, especially under allo-PBMC induced immuno-rejection. In conclusion, our study shows that AD-MSC is a powerful candidate to minimize immunological rejection and improve vessel formation in EPC transplantation treatment.
Highlights
Endothelial progenitor cells (EPCs) are considered a cellular resource for differentiation into vascular endothelial cells [1]
Adipocyte and osteocyte induction was easier in adipose tissue (AD)-mesenchymal stem cells (MSCs) than umbilical cord (UC)-MSCs (Fig 1C and 1D)
EPCs or EPCs + umbilical cord-derived MSCs (UC-MSCs), while no red blood cell leakage was observed in grafts containing EPCs + adipose-derived MSCs (AD-MSCs) (Fig 5). It is well-known that EPC could be a valuable cellular resource for patients who suffer from cardiovascular disease or ischemic disease [7,16]
Summary
Endothelial progenitor cells (EPCs) are considered a cellular resource for differentiation into vascular endothelial cells [1]. EPCs can promote neovascularization at the site of vascular injury or de novo neovascularization [2]. Many studies suggested that transplanted EPCs could regenerate damaged vessels and ameliorate symptoms of ischemic diseases [3]. MSCs modulate the immunogenicity of EPCs quality of life for patients who suffer from peripheral arterial diseases [4]. These studies showed transplantation of autologous EPCs could become a new cell-based therapeutic strategy for vascular disease or ischemic disease treatment. Transplantation of allogenic EPCs may provide a novel and useful potential therapeutic technique for treating vascular diseases or ischemic diseases
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