Regenerating the Cardiovascular System Through Cell Reprogramming; Current Approaches and a Look Into the Future

Abstract

Cardiovascular disease (CVD), despite the advances of the medical field, remains one of the leading causes of mortality worldwide. Discovering novel treatments based on cell therapy or drugs is critical, and induced pluripotent stem cells (iPS Cells) technology has made it possible to design extensive disease-specific in vitro models. Elucidating the differentiation process challenged our previous knowledge of cell plasticity and capabilities and allows the concept of cell reprogramming technology to be established, which has inspired the creation of both in vitro and in vivo techniques. Patient-specific cell lines provide the opportunity of studying their pathophysiology in vitro, which can lead to novel drug development. At the same time, in vivo models have been designed where in situ transdifferentiation of cell populations into cardiomyocytes or endothelial cells (ECs) give hope toward effective cell therapies. Unfortunately, the efficiency as well as the concerns about the safety of all these methods make it exceedingly difficult to pass to the clinical trial phase. It is our opinion that creating an ex vivo model out of patient-specific cells will be one of the most important goals in the future to help surpass all these hindrances. Thus, in this review we aim to present the current state of research in reprogramming toward the cardiovascular system's regeneration, and showcase how the development and study of a multicellular 3D ex vivo model will improve our fighting chances.

Enhancing Stem Cell-Based Therapeutic Potential by Combining Various Bioengineering Technologies

“…Other major challenges associated with the application of vascular cells in cardiovascular diseases are the poor quality and quantity of proliferating cells, which deteriorates with the donor’s age and also depends on the selected cell type and isolation method ( Janzen et al, 2006 ; Mimeault and Batra, 2009 ). In this context, various types of stem/progenitor cells are being used as sources of endothelial cells, smooth muscle cells, and vascular cells to facilitate vascular regeneration and incorporation into the engineered vasculature ( Tsifaki et al, 2018 ; Vila Cuenca et al, 2021 ). In particular, MSCs from bone marrow or adipose tissues are an attractive source of vascular cells for tissue bioengineering ( Pittenger et al, 2019 ).…”

Derivation of endothelial cells from porcine induced pluripotent stem cells by optimized single layer culture system

“…Endothelial cells (ECs) are cells lining the luminal surface of blood and lymphatic vessels, and ECs in direct contact with blood are referred to as vascular ECs [1]. Loss or dysfunction of vascular ECs usually results in vascular diseases such as atherosclerosis, which can seriously affect human health [2]. Human induced PSCs (iPSCs) are a promising cell source for autotransplantation when treating vascular diseases [3] and have properties similar to those of embryonic stem cells (ESCs) [4,5].…”