San Diego Regenerative Medicine Institute, Xcelthera, La Jolla IVF, and Sanford Consortium for Regenerative Medicine announce the publication of collaborative original research, titled “Defining Conditions for Sustaining Epiblast Pluripotence Enables Direct Induction of Clinically-Suitable Human Myocardial Grafts from Biologics-Free Human Embryonic Stem Cells”. To date, lacking of a clinically-suitable human cardiac cell source with adequate myocardium regenerative potential has been the major setback in regenerating the damaged human heart. Pluripotent human embryonic stem cells (hESCs) proffer unique revenue to generate a large supply of cardiac lineage-committed cells as human myocardial grafts for cell-based therapy. Due to the prevalence of heart disease worldwide and acute shortage of donor organs or human myocardial grafts, there is intense interest in developing hESC-based therapy for heart disease and failure. However, realizing the therapeutic potential of hESCs has been hindered by the inefficiency and instability of generating cardiac cells from pluripotent cells through uncontrollable multi-lineage differentiation. In addition, the need for foreign biologics for derivation, maintenance, and differentiation of hESCs may make direct use of such cells and their derivatives in patients problematic. Understanding the requirements for sustaining pluripotentce and self-renewal of hESCs will provide the foundation for de novo derivation and long-term maintenance of biologics-free hESCs under optimal yet well-defined culture conditions from which they can be efficiently directed towards clinically-relevant lineages for cell therapies. We previously reported the resolving of the elements of a defined culture system, serving as a platform for effectively directing pluripotent hESCs uniformly towards a cardiac lineage-specific fate by small molecule induction. In this study, we found that, under the defined culture conditions, primitive endoderm-like (PEL) cells constitutively emerged and acted through the activin-A-SMAD pathway in a paracrine fashion to sustain the epiblast pluripotence of hESCs. Such defined conditions enable the spontaneous unfolding of inherent early embryogenesis processes that, in turn, aid efficient clonal propagation and de novo derivation of stable biologics-free hESCs from blastocysts that can be directly differentiated into a large supply of clinically-suitable human myocardial grafts across the spectrum of developmental stages using small molecule induction for cardiovascular repair. This original research article of Parsons et al was published in Journal of Clinic. Exp. Cardiology Special Issue on Heart Transplantation.
Cardiovascular disease (CVD) is a major health problem and the leading cause of death in the Western World. In the United States, around 5 millions survive heart failure but live with insufficient cardiac function, and about 550,000 new cases are diagnosed annually. Heart attacks, known as myocardial infarction (MI), are the main cause of death in patients with CVD. Around 1/3 of the patients suffering from heart attacks each year die suddenly before reaching the hospital. In the remaining patients who survive their initial acute event, the damage sustained by the heart may eventually develop into heart failure, with an estimated median survival of 1.7 years in men and 3.2 years in women. To date, lacking of a suitable human cardiomyocyte 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. In the adult heart, the mature contracting cardiac muscle cells, known as cardiomyocytes, are terminally differentiated and unable to regenerate. Damaged or diseased cardiomyocytes are removed largely by macrophages and replaced by scar tissue. Although cell populations expressing stem/progenitor cell markers have been identified in the adult hearts, the minuscule quantities and growing evidences indicating that they are not genuine heart cells have caused skepticism if they can potentially be harnessed for cardiac repair. There is no evidence that stem cells derived from patients’ heart tissues, such as Cedars-Sinai’s Eduardo Marban’s autologous heart tissue cells (who said the last thing he would do was hESC research, maybe the last thing he should cheat was taking Prop 71 fund for hESC research from California Institute for Regenerative Medicien [CIRM] if he has any professor’s ethics), are able to give rise to the contractile heart muscle cells following transplantation into the heart. There is no evidence that stem cells derived from other sources, such as bone marrow or umbilical cord or cord blood, are able to give rise to the contractile heart muscle cells following transplantation into the heart. Therefore, the need to regenerate or repair the damaged heart muscle (myocardium) has not been met in today's healthcare industry. Heart transplantation with the donor organ has been the only definitive treatment for end-stage heart failure. For millions living with the damaged heart, there is no alternative definitive treatment available at present time. For patients who need the heart transplantation, there is an acute shortage of donor organs. Many patients die while waiting on the shortlist.
Pluripotent human embryonic stem cells (hESCs), derived from the inner cell mass (ICM) or epiblast of the human blastocyst, proffer unique revenue to generate a large supply of cardiac lineage-committed cells as adequate human myocardial grafts for cell-based therapy. 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 hESC-based therapy for heart disease and failure. The hESCs and their derivatives are considerably less immunogenic than adult tissues. It is also possible to bank large numbers of human leukocyte antigen isotyped hESC lines so as to improve the likelihood of a close match to a particular patient in order to improve the engraftment and survival efficiency, and minimize the potential risk and side-effect of immune rejection following transplantation. However, there are 2 major obstacles to bring hESC therapy to clinics. One major obstacle to translate hESC biology is that most currently-available hESC lines were derived and maintained on animal cells and proteins, therefore, those hESCs have been contaminated with animal biologics and cannot be used for patients in clinical trials. The other major obstacle to develop hESC therapy is very difficult to channel the wide differentiation potential of hESCs in order to generate a large supply of uniform functional cells as the cell therapy product targeting for a particular disease. Our breakthroughs have overcome both obstacles, enabling both de novo derivation of clinical-grade cGMP (Current Good Manufacturing Practices) compatible hESCs from blastocysts (Xcel-hESCs) that have never been contaminated by animal cells and proteins, and a large supply of clinical-grade functional cardiac precursors and cardiomyocytes to be translated to patients in clinical trials for mending the heart. The heart is the first organ formed from the cells of the ICM/epiblast of the blastocyst in early embryogenesis. The hESC-derived embryonic heart cells resemble the heart cells in human development, therefore, they have the powerful potential to form human contractile heart muscle as well as the cardiovascular structure with intact 3D geometry and vasculature of the whole heart. The availability of a large supply of clinically-grade human myocardial grafts in high purity and large quantity with adequate potential to mend the heart makes heart disease possible to be the first major health problem to be cured by clinical translation of human embryonic stem cell research.
no stem cell in umbilical cord, another korean scam.
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