The Use of Mesenchymal Stromal Cells and Tissue-Engineered Blood Vessels for Seamless Implant Integration

Abstract

In recent years, organ transplantation technology has made significant improvements regarding long-term survival, substantially decreasing the risk of graft rejection. However, with each passing year,the gap between available donors and the number of patients needing an organ transplant is steadilyincreasing. Consequently, there is a growing demand to create engineered tissues to minimize the needfor organ transplantation. However, the rejection of engineered tissue implants has become a criticalchallenge today. Primarily, rejection occurs due to the crosstalk between immune cells, such asmacrophages, and the engineered tissue structure. Therefore, it is important to be able to influence theimmune cell milieu of the implantation site to achieve graft integration. With this perspective in mind,this doctoral thesis aimed to provide two different strategies: The first one is the use of human hairfollicle derived mesenchymal stromal cells (HF-MSCs) for immunomodulation. For that, we isolate andcharacterize MSCs from human hair follicles and then, we analyzed the immunomodulatory capacity ofthe cells by means of the inhibition of peripheral mononuclear cells (PBMCs), inducing T regulatoryphenotype and skewing macrophages towards a tissue remodeling phenotype (aka M2). The secondstrategy relied on the application of tissue-engineered blood vessels to interact with different macrophagephenotypes and thus promoting a tissue remodeling response around the implant. The effects of bloodvessels on undifferentiated (M0), pro-inflammatory (M1) and regenerative (M2 and M1M2) macrophagephenotypical change were assessed by single cell analysis, specifically using dimensionality reductionand clustering algorithms for a thorough characterization of resulted macrophage phenotype. Therefore,we could conclude that both strategies could have an important developmental impact towards theimplementation of immunomodulatory techniques and could have important consequences for tissue engineering.