The Promise and Challenge of Induced Pluripotent Stem Cells for Cardiovascular Applications

Abstract

SummaryThe recent discovery of human-induced pluripotent stem cells (iPSC) has revolutionized the field of stem cells. iPSC have demonstrated that biological development is not an irreversible process and that mature adult somatic cells can be induced to become pluripotent. This breakthrough is projected to advance our current understanding of many disease processes and revolutionize the approach to effective therapeutics. Despite the great promise of iPSC, many translational challenges still remain. The authors review the basic concept of induction of pluripotency as a novel approach to understand cardiac regeneration, cardiovascular disease modeling, and drug discovery. They critically reflect on the current results of pre-clinical and clinical studies using iPSC for these applications with appropriate emphasis on the challenges facing clinical translation.

Engineering of Mature Human Induced Pluripotent Stem Cell‐Derived Cardiomyocytes Using Substrates with Multiscale Topography

“…Transplantation of CMs that are differentiated from iPSCs (iCMs) is preferable to direct use of iPSCs due to the enhanced functionality and reduced risk of tumor formation . In addition to their therapeutic benefits in myocardial salvage and regeneration, iCMs have also demonstrated great potential to simulate myocardium for the purposes of drug screening (e.g., chemotherapeutic drugs in cancer patients), and have proven superior to other approaches including neonatal nonhuman cells due to the inherent physiological differences between species . Finally, CMs are excellent bioactuators, capable of transforming electrical signals into mechanical work in biorobotics applications…”

Innovation for hepatotoxicity in vitro research models: A review

“…Genetic alterations and differentiation-induced heterogeneity that occur during the reprogramming process are limitations of iPSCs/HLCs models (Ferrer et al, 2014;Soldner & Jaenisch, 2012). In addition, not all human diseases can be modeled in vitro using iPSCs because of the complex interactions between environmental and multiple genetic factors, or their long incubation period (Youssef et al, 2016).…”

Differentiation and Application of Induced Pluripotent Stem Cell–Derived Vascular Smooth Muscle Cells

“…74 For tissue engineering approaches, poor cellular engraftment remains an issue in stem cell-based therapies. 73 Techniques seeking to improve their adhesion and integration into host tissue are vital if iPSC-derived tissue engineering is to be pursued. Reports of transplanted stem cells releasing soluble factors, resulting in a paracrine effect on neighboring cells, 85,86,101 would suggest that iPSC-derived VSMCs contribute to cardiovascular repair and regeneration may occur through a similar manner as seen with the study by Hibino et al 102 using iPSC sheets.…”

“…Moreover, another issue arising from iPSC-derived VSMCs for surgical treatment is the time-consuming nature of generating patient-specific VSMCs followed by seeding onto a scaffold for 3D tissue engineering, especially in an acute setting such as a myocardial infarct where patients require immediate surgical intervention. 73 Finally, but most importantly, the risks of tumorigenesis and teratoma formation for transplanted iPS cell-derived VSMCs must be carefully considered before clinical application. Thus, as of yet the clinical benefit of iPSC technology has not reached its full potential.…”