Editorial: Exploring Future Cardiovascular Medicine: Heart Precursors Directed from Human Embryonic Stem Cells for Myocardium Regeneration

San Diego Regenerative Medicine Institute and Xcelthera announce Dr. Parsons’ Editorial, titled “Exploring Future Cardiovascular Medicine: Heart Precursors Directed from Human Embryonic Stem Cells for Myocardium Regeneration” (doi: 10.4172/cpo.1000e110), published in current issue of The International Open Access Journal of Cardiovascular Pharmacology.

Given the limited capacity of the heart muscle for self-repair after birth, transplantation of cardiomyocyte stem/precursor/progenitor cells holds enormous potential in cell replacement therapy for cardiac repair. However, the lack of a clinically-suitable human cardiomyocyte stem/precursor/progenitor cell source with adequate myocardium regenerative potential has been the major setback in regenerating the damaged human heart, either by endogenous cells or by cell-based transplantation or cardiac tissue engineering. Due to the prevalence of heart disease worldwide and acute shortage of donor organs or adequate human myocardial grafts, there is intense interest in developing human embryonic stem cell (hESC)-based therapy for heart disease and failure. However, realizing the developmental and therapeutic potential of hESC derivatives has been hindered by the inefficiency and instability of generating clinically-relevant functional cells from pluripotent cells through conventional uncontrollable and incomplete multi-lineage differentiation. In addition, undefined foreign or animal biological supplements and/or feeders that have typically been used for the isolation, expansion, and differentiation of hESCs may make direct use of such cell-specialized grafts in patients problematic. Recent technology breakthroughs in hESC research have overcome some major obstacles in bringing hESC therapy derivatives towards clinical applications, including establishing defined culture systems for derivation and maintenance of clinical-grade pluripotent hESCs and lineage-specific differentiation of pluripotent hESCs by small molecule induction. Such milestone advances and medical innovations in hESC research enable direct conversion of pluripotent hESCs into a large supply of homogeneous populations of clinical-grade hESC neuronal and heart cell therapy products for developing safe and effective stem cell therapies. Currently, these hESC neuronal and cardiomyocyte therapy derivatives are the only available human cell sources with adequate capacity to regenerate neurons and contractile heart muscles, vital for CNS and heart repair in the clinical setting. This novel small molecule direct induction approach renders a cascade of neural or cardiac lineage-specific progression directly from the pluripotent state of hESCs, providing much-needed in vitro model systems for investigating the genetic and epigenetic programs governing the human embryonic CNS or heart formation. Please read Dr. Parsons’ editorial at http://www.esciencecentral.org/journals/ArchiveCPO/currentissueCPO.php.

Direct Conversion of Pluripotent Human Embryonic Stem Cells into Functional Cell Therapy Derivatives Brings Cell-Based Regenerative Medicine to a Turning Point

San Diego Regenerative Medicine Institute and Xcelthera announce the publication of Dr. Parsons’ review article, titled “Constraining the Pluripotent Fate of Human Embryonic Stem Cells for Tissue Engineering and Cell Therapy – The Turning Point of Cell-Based Regenerative Medicine”, in British Biotechnology Journal at http://www.sciencedomain.org/issue.php?iid=243&id=11. In this review article, Dr. Parsons gives an insight view on recent advances and breakthroughs in human embryonic stem cell (hESC) research that have overcome some major obstacles in bringing hESC therapy derivatives towards clinical applications, including establishing defined culture systems for de novo derivation and maintenance of clinical-grade pluripotent hESCs and lineage-specific differentiation of pluripotent hESCs by small molecule induction. This technology breakthrough enables direct conversion of pluripotent hESCs into a large supply of high purity neuronal cells or heart muscle cells with adequate capacity to regenerate CNS neurons and contractile heart muscles for developing safe and effective stem cell therapies. Transforming pluripotent hESCs into fate-restricted therapy derivatives dramatically increases the clinical efficacy of graft-dependent repair and safety of hESC-derived cellular products. Such milestone advances and medical innovations in hESC research allow generation of a large supply of clinical-grade hESC therapy derivatives targeting for major health problems, bringing cell-based regenerative medicine to a turning point.

Human stem cell therapy derivatives are extremely attractive for therapeutic development because they have direct pharmacologic utility in clinical applications, unlike any cells originated from animals and other lower organisms that are only useful as research materials. The human stem cell is emerging as a new type of pharmacologic agent of cellular entity in cell-based regenerative medicine, because human stem cell therapy derivatives have the potential for human tissue and function restoration that the conventional drug of molecular entity lacks. The ability of a human stem cell, by definition, to both self-renew and differentiation makes it a practically inexhaustible source of replacement cells for many devastating or fatal diseases that have been considered as incurable, such as neurodegenerative diseases and heart diseases. The pharmacologic activity of human stem cell therapy derivatives is measured by their extraordinary cellular ability to regenerate the tissue or organ that has been damaged or lost. In this regard, the pharmacologic utility of human stem cells cannot be satisfied only by their chaperone activity, if any, to produce trophic or protective molecules to rescue existing endogenous host cells that can simply be achieved by a small molecule or a drug of molecular entity. There is a large unmet healthcare need to develop human embryonic stem cell (hESC)-based stem cell therapies to provide optimal regeneration and reconstruction treatment options to restore normal tissues and function. Clinical applications of hESC therapy derivatives provide the right alternative for many incurable diseases and major health problems that the conventional mode of drugs and treatments cannot.

We must bear in mind that the pluripotent hESC itself cannot be used for therapeutic applications. It has been recognized that pluripotent hESCs must be transformed into fate-restricted derivatives before use for cell therapy. Conventional approaches rely on multi-lineage inclination of pluripotent cells through spontaneous germ layer differentiation, which yields embryoid body (EB) consisting of a mixed population of cell types that may reside in three embryonic germ layers and results in inefficient, incomplete, and uncontrollable differentiation that is often followed by phenotypic heterogeneity and instability, hence, a high risk of tumorigenicity. Growing evidences indicate that incomplete lineage specification of pluripotent cells via multi-lineage differentiation often resulted in poor performance of such stem cell derivatives and/or tissue-engineering constructs following transplantation. In addition, most currently available hESC lines were derived and maintained on animal feeder cells and proteins, therefore, such hESCs have been contaminated with animal biologics and unsuitable for clinical application. Without a practical strategy to convert pluripotent cells direct into a specific lineage, previous studies and profiling of hESC differentiating multi-lineage aggregates have compromised their implications to molecular controls in human embryonic development.

Recent advances and technology breakthroughs in hESC research have overcome some major obstacles in bringing hESC therapy derivatives towards clinical applications, including establishing defined culture systems for de novo derivation of clinically-suitable stable hESC lines from human blastocysts that have never been contaminated by animal cells and proteins, and direct conversion of such pluripotent hESCs into a large supply of clinical-grade functional human neuronal or cardiomyocyte therapy derivatives to be translated to patients for CNS or heart repair. Without an understanding of the essential developmental components for sustaining hESC pluripotence and self-renewal, hESC lines are at risk for becoming unhealthy and unstable after prolonged culturing under animal feeders, feeder-conditioned media, or artificially-formulated chemically-defined conditions. Resolving minimal essential requirements for sustaining embryonic pluripotence allows all poorly-characterized and unspecified biological additives, components, and substrates in the culture system, including those derived from animals, to be removed, substituted, or optimized with defined human alternatives for de novo derivation and long-term maintenance of GMP-quality xeno-free stable hESC lines and their human therapy derivatives. Formulation of minimal essential defined conditions renders pluripotent hESCs be directly and uniformly converted into a specific neural or cardiac lineage by small signal molecule induction. Such milestone advances and medical innovations in hESC research enable generation of a large supply of high purity clinical-grade hESC neuronal and heart muscle cell therapy products as powerful cellular medicines that can offer pharmacologic utility and capacity for CNS and heart regeneration that no conventional drug of molecular entity can. Currently, these hESC neuronal and cardiomyocyte therapy derivatives are the only available human cell sources with adequate capacity to regenerate neurons and contractile heart muscles, vital for CNS and heart repair in the clinical setting. The availability of human neuronal and cardiomyocyte therapy derivatives in high purity and large quantity with adequate potential for CNS and myocardium regeneration will facilitate CNS and myocardial tissue-engineering and accelerate the development of safe and effective cell-based therapy to resolve these major health problems. Further improving policy making and funding situation for hESC research would open up a new dimension of cell therapy-based future medicine to provide new medical treatments for many devastating and life-threatening diseases and injuries. Transforming pluripotent hESCs into fate-restricted therapy derivatives dramatically increases the clinical efficacy of graft-dependent repair and safety of hESC-derived cellular products, bringing cell-based regenerative medicine to a turning point. Please read Dr. Parsons’ full open access article at http://www.sciencedomain.org/issue.php?iid=243&id=11.