oa Realizing the Promises of Pluripotent Stem Cells: Discovering Fundamental Biological Principles, New Medical Options and Enriching Friendships via Scientific Diplomacy Globally

Pluripotent stem cells from humans (hPSCs), including human embryonic stem cells (hESCs) and PSCs generated by induced pluripotency (hiPSCs), captivate biomedical attentions due to their unique properties of unlimited self-renewal and pluripotent differentiation. As immortal gametic lineages are differentiated from PSCs, especially spermatogenic cells, the previous distinction between mortal somatic cells and potentially immortal germ cells is now blurred with bioethical and even metaphysical implications. ESC lines have only been established robustly and investigated intensively in mice (mESCs) and more recently in humans after derivations from fertilized-blastocysts and now after induced pluripotency (iPSCs). Scientists around the world are now asking whether these cells might treat or even cure juvenile diabetes with insulin secreting β-islet cells responsive to circulating glucose; cerebral palsy treatments with neuroprogenitors to repair white matter injuries due to premature births; heart muscle repair with cardiomyocytes; spinal cord regeneration with peripheral motor neurones; multiple sclerosis with neuroprogenitor cells or astrocytes for Schwann cell; Parkinson’s disease using dopaminergic neurones; amyotrophic lateral sclerosis with neuronal lineages; reduction or replacement of whole organ transplantation by single cell transplantation of hepatocytes for diseased livers; renal cells in place of kidney transplants, and many others. Study of hESCs and other pluripotent cells is vital for understanding the processes that lead to healthy babies, infants, and children – since it provides invaluable insights into the development of viable gametes, successful fertilisation and embryogenesis, and optimal implantation and uneventful pregnancy, all essential for the birth of the healthiest baby with every opportunity.

Investigations into hESCs may also determine the causes of birth defects, low-birth weight and prematurity, spontaneous recurrent miscarriages, preeclampsia, germ cell tumours, epigenetic diseases, and infertility. However, hESCs are pluripotent and potentially immortal. Consequently, they have the theoretical capacities to proliferate, migrate, and differentiate indefinitely. These properties are shared with cells having malignant potential, which raises the question of whether they might result in malignancies after transplantation, e.g. teratomas, inappropriate transdifferentiation (from, say, neurones into bone or muscle), antigen exposure and immune reactions, and neovascularization. These critical problems in stem cell research offer revolutionary therapeutic advances, yet raise seemingly irresolvable science policy controversies, in part because so much of the evidence derived from murine investigations may not be accurately extrapolated to humans. To address this issue, we have also derived non-human primate ESCs from in vitro-derived primate embryos and after both induced pluripotency as well as nuclear transfer to examine the fundamental biology of pluripotent stem cells during development and differentiation. The use of non-invasive imaging techniques, such as positron emission tomography and magnetic resonance imaging to monitor non-human primate embryonic stem cells after transplantation will be presented. Stem cell dynamics in vitro, in utero and in vivo will all be discussed in relation to transplantation potentials of ES cells, with special attention devoted to possible use of male PSCs to help restore fertility in boys who have been successfully treated for cancer – but have been rendered infertile by their therapy.

Sponsored by the National Institutes of Health.