Journal of Cell Science & Therapy
Open Access
ISSN: 2157-7013
+44 1300 500008
ISSN: 2157-7013
+44 1300 500008
Xuejun H. Parsons
Scientific Tracks Abstracts: J Cell Sci Ther
P luripotent human embryonic stem cells (hESCs) have unlimited expansion ability and unrestricted intrinsic plasticity for differentiation into all somatic cell types in the human body, holding tremendous potential for restoring tissue and organ function. However, realizing the developmental and therapeutic potential of hESCs has been hindered by the inefficiency and instability of generating functional cells through multi-lineage differentiation of pluripotent cells, which is uncontrollable, inefficient, highly variable, difficult to reproduce and scale-up. Developing novel strategies for the intrinsic developmental programs of pluripotent hESCs to systematically unfold in a lineage-specific manner is vital to harnessing the power of hESC biology for cell-based therapy. To tackle the shortcomings in conventional approaches, we found that pluripotent hESCs maintained under the defined culture conditions can be uniformly converted into a specific lineage by small molecule induction. Retinoic acid was found to induce the specification of neuroectoderm direct from the pluripotent state of hESCs and trigger progression to neuronal progenitors and neurons efficiently. Similarly, nicotinamide was found to induce the specification of cardiomesoderm direct from the pluripotent state of hESCs and trigger progression to cardiac precursors and cardiomyocytes efficiently. To uncover key regulators, microRNA expression profiling using microarrays was used to identify novel sets of human embryonic development initiating miRNAs upon lineage specific differentiation direct from the pluripotent stage of hESCs. A unique set of pluripotence-associated miRNAs was down-regulated, while novel sets of distinct cardiac- and neural-driving miRNAs were up-regulated in lineage specific differentiation of pluripotent hESCs, including silencing of the most prominent pluripotence-associated hsa-miR-302 family and a drastic expression increase of Hox miRNA hsa-miR-10 family upon neural induction. This technology breakthrough enables well-controlled generation of a large supply of cardiac/neural lineage-specific progenies across the spectrum of developmental stages direct from the pluripotent state of hESCs with small molecule induction. To date, lacking of clinically-suitable human neuronal/cardiomyocyte cell sources has been the major setback in developing cell- based therapies for restoring the damaged or lost nerve tissues/myocardium in CNS/heart diseases. The availability of human neuronal/cardiac cells in high purity and large quantity with adequate neurogenic/cardiogenic potential will accelerate the development of effective cell-based therapies against CNS/heart diseases
Xuejun H. Parsons obtained her PhD from Cornell University in 1998 and completed her postdoctor as Leukemia and Lymphoma Society Research Follow in University of California at San Diego in 2002. Since, her career transition to the human stem cell field has been supported by NIH Career Development/Eunice Kennedy Shriver Awards. She is the co-founder and scientific director of San Diego Regenerative Medicine Institute and the founder of Xcelthera, emerging with world-class leadership and expertise in human embryonic stem cell (hESC)-based regenerative medicine for development of hESC-derived neuronal/cardiac therapeutic products and technology of directed lineage-specific differentiation of pluripotent hESCs.