Abstract
Personalized regenerative medicine and biomedical research have been galvanized and revolutionized by human pluripotent stem cells in combination with recent advances in genomics, artificial intelligence, and genome engineering. More recently, we have witnessed the unprecedented breakthrough life-saving translation of mRNA-based vaccines for COVID-19 to contain the global pandemic and the investment in billions of US dollars in space exploration projects and the blooming space-tourism industry fueled by the latest reusable space vessels. Now, it is time to examine where the translation of pluripotent stem cell research stands currently, which has been touted for more than the last two decades to cure and treat millions of patients with severe debilitating degenerative diseases and tissue injuries. This review attempts to highlight the accomplishments of pluripotent stem cell research together with cutting-edge genomics and genome editing tools and, also, the promises that have still not been transformed into clinical applications, with cardiovascular research as a case example. This review also brings to our attention the scientific and socioeconomic challenges that need to be effectively addressed to see the full potential of pluripotent stem cells at the clinical bedside.
Highlights
The capacity to proliferate indefinitely, as well as the ability to differentiate into almost all phenotypic cells that constitute a mature organism, make human pluripotent stem cells an attractive versatile cellular source for cell replacement therapies for many degenerative diseases, such as ischemic heart failure, diabetes, Parkinson’s and Alzheimer’s diseases, and age-related macular degeneration and tissue injuries [1,2].Three types of hPSCs have been reported so far
These limitations were overcome by hPSC-based in vitro disease modeling, which has provided an unlimited supply of the relevant phenotypic cells from hPSCs derived either from the respective patients and their family matched controls or from the creation of isogenic cell lines from a control hPSC cell line with the relevant mutations genetically engineered with genome-editing tools such as ZFN, TALENs, and CRIPSPR methodologies
This study showed how to estimate the pathogenicity of variants of uncertain significance in patient-specific human-induced pluripotent stem cells (hiPSCs) and their differentiated cells [12,75,77]
Summary
The capacity to proliferate indefinitely, as well as the ability to differentiate into almost all phenotypic cells that constitute a mature organism, make human pluripotent stem cells (hPSCs) an attractive versatile cellular source for cell replacement therapies for many degenerative diseases, such as ischemic heart failure, diabetes, Parkinson’s and Alzheimer’s diseases, and age-related macular degeneration and tissue injuries [1,2]. The third type of hPSCs is derived by somatic cell nuclear transfer, a strategy that was very popular in 1996 with the creation of the sheep Dolly, by which a nucleus from a differentiated cell is transferred into a denucleated ovum [9,10] The derivation of this latter type of hPSC remains technically challenging and is rarely used [11]. Among these three different types of hPSCs, only hESCs and hiPSCs have been largely explored for regenerative medicine and clinical applications, and these two hPSC types have revolutionized biomedical research and regenerative medicine with their unprecedented potential opportunities for cell replacement therapies for many degenerative diseases and injuries [2] for the last two decades ever since their discovery. We highlight the scientific advances made in biomedical research and regenerative medicine by hPSC technology, along with the high-throughput genomic and gene-editing methodologies and, what we have not learned or not achieved so far with these combined technologies from their earlier anticipated speculative milestones that the scientific community once were hopeful of achieving, with a specific focus on cardiovascular research
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