Clinical applications of patient-specific induced pluripotent stem cells in cardiovascular medicine

Abstract

The emergence of induced pluripotent stem cell (iPSC) technology has had a great impact on the field of medicine ever since the ground-breaking discovery in 2006 that overexpression of four specific transcription factors was able to turn back the developmental clock of somatic cells into an embryonic-like state. The resulting iPSCs carry the developmental potential of human embryonic stem cells (hESC) without the embryo and have been heralded as a powerful tool to study development and disease. This technology has made it possible for the first time for researchers to transform end-differentiated cells from a particular individual into another cell type that remains specific to that individual, paving the way for novel methods of in vitro disease modelling and therapeutic applications. This paper reviews some of the key areas in cardiovascular medicine in which iPSC technology has been applied and discusses the future directions and ongoing challenges ahead in this exciting field.

Perspectives of induced pluripotent stem cells for cardiovascular system regeneration

“…They can be divided into integrating and non-integrating methods. 13,14 Integrative delivery system. Most of the iPSC lines established to date have been generated using integrating retroviral and lentiviral vectors to deliver reprogramming factors.…”

“…There are difficulties in ensuring a purified cardiomyocytes population from iPSCs through standard cardiomyocytes differentiation protocols; the complexities of reproducing a heterogeneous disease phenotype which may involve other systematic factors in vitro using only cardiomyocytes; and limitations of modeling essentially adult-onset diseases using iPSC-cardiomyocytes with a predominantly fetal-like phenotype. 13 Resolving these obstacles will also have great impact on facilitating in vivo studies and widespread applications in drug discovery and development. 67 …”

“…26 Hematopoietic stem and progenitor cells give rise to iPSCs up to 300 times more efficiently than terminally differentiated B and T cell, yielding reprogramming efficiencies of up 28%. 13 Human adipose tissue is also rich source of multipotent stem cells, which can be obtained by liposuction. These human adipose stem cells can differentiate into adipogenic, osteogenic, chondrogenic, and myogenic cell lineages and can be reprogrammed into iPSCs with 20-fold greater efficiency and two-fold faster as compared to adult fibroblast reprogramming.…”

“…Enthusiasm for use of iPSC technology in regenerative medicine has been hampered by the increasingly recognized problems of the unpredictable nature and behavior of transplanted iPSCs and the potential for these cells to cause harm. 13,48 For cardiovascular regeneration, more robust selection markers and refined experimental protocols are required to reproducibly guide iPSCs to cardiovascular lineage. Moreover, effective negative selection against pluripotent cells is necessary to avoid teratoma formation by contaminating pluripotent stem cells.…”

“…32 Cardiomyocytes differentiation and purification iPSC colonies can be differentiated into functional cardiomyocytes using a variety of methods, which are very similar to those traditionally employed to produce cardiomyocytes from human ESCs since both iPSCs and human ESCs share very similar characteristics and differentiation potential. 13 There are several protocols, which are available for cardiac differentiation from human pluripotent stem cells (hPSCs): the embryoid body (EB) culture system, the monolayer culture system, and the inductive co-culture system. 5,33 The differentiation of iPSCs into cardiomyocytes in vitro was firstly reported in murine iPSCs lines in 2008.…”