Abstract
The discovery of induced pluripotent stem cells (iPSCs) has made an invaluable contribution to the field of regenerative medicine, paving way for identifying the true potential of human embryonic stem cells (ESCs). Since the controversy around ethicality of ESCs continue to be debated, iPSCs have been used to circumvent the process around destruction of the human embryo. The use of iPSCs have transformed biological research, wherein increasing number of studies are documenting nuclear reprogramming strategies to make them beneficial models for drug screening as well as disease modelling. The flexibility around the use of iPSCs include compatibility to non-invasive harvesting, and ability to source from patients with rare diseases. iPSCs have been widely used in cardiac disease modelling, studying inherited arrhythmias, neural disorders including Alzheimer’s disease, liver disease, and spinal cord injury. Extensive research around identifying factors that are involved in maintaining the identity of ESCs during induction of pluripotency in somatic cells is undertaken. The focus of the current review is to detail all the clinical translation research around iPSCs and the strength of its ever-growing potential in the clinical space.
Highlights
The science around terminal inactivation and deletion of genetic codes of heredity in somatic cells was postulated by the Weismann barrier theory [1]
The somatic cell nuclear transfer (SCNT) demonstration asserted the fact that the genetic code in somatic cells is not discarded, and that reactivation of the same is a possibility through careful manipulations [2]
Developmental biology entered a new dimension of achievement when the discovery of embryonic stem cells (ESCs) and their pluripotency was exhibited, and further research identified that on fusion of somatic cells like fibroblasts, and T-lymphocytes with ESCs, reprogramming of the former through expression of genes associated with pluripotency becomes a possibility [3,4]
Summary
The science around terminal inactivation and deletion of genetic codes of heredity in somatic cells was postulated by the Weismann barrier theory [1]. Research has identified possibility of successful reprogramming using microRNAs (miRNAs) which exhibit improved efficiency, wherein use of c-Myc has been replaced with miR-291-3p, miR-294, and miR-295 to generate homogenous colonies of human iPSCs [17]. Though the four most popular reprogramming factors have been Oct, Sox, Klf, and c-Myc, human iPSCs have been derived using expression of Oct, Sox, Nanog, and Lin, indicating that pluripotent ground state becomes achievable through activation of different transcription factors [21]. The CRISPR/Cas gene editing system was used to correct the cDNA in the HB-iPSCs and the resultant hepatocyte-like cells exhibited restored synthesis ability for clotting factor IX. The CRISPR/Cas system was used to correct the mutation in CALM2 and the resultant gene corrected iPSC-derived cardiomyocytes showed reversal in electrophysiological abnormalities with successfully recapitulating the disease phenotype. The gene correct iPSCs successfully differentiated to mature airway epithelial cells and recovered normal CFTR expression
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