Molecular regulation of cell survival and cellular interactions of pluripotent stem cells

Funding Type: 
Basic Biology II
Grant Number: 
RB2-01602
ICOC Funds Committed: 
$0
Disease Focus: 
Epilepsy
Neurological Disorders
Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 
The recent technological breakthrough has paved the way to convert adult differentiated cells such as skin cells into undifferentiated cells called human induced pluripotent stem (hiPS) cells that have an ability (pluripotency) to become all types of adult cells in human body. Because of this enormous ability, hiPS cells are thought to be the potential source of the cell-transplantation therapy for the treatment of diseases such as Parkinson's disease and diabetes mellitus. Despite this promising function of hiPS cells, due to its short history, there are many biological questions and practical hurdles to overcome. One questions is how we can distinguish fully converted genuine iPS cells from incompletely converted cells. Other important issues include development of technologies to derive and grow hiPS cells at high efficiency under completely animal-free conditions for future medical purposes. We have recently identified a signaling pathway (like a hormone that mediates biological information) that controls cell-cell attachment of pluripotent stem cells. Moreover, by controlling this pathway, we have established a method to grow another type of pluripotent cells, human embryonic stem (hES) cells, in a fully animal-free condition. In this proposal, we will investigate whether measuring the activity of this pathway could be helpful to select genuine iPS cells. Furthermore, by using this technology, we will develop a new method to efficiently generate and expand a new hiPS cell lines that are completely free from animal-derived materials.
Statement of Benefit to California: 
Our research will focus on developing novel technologies by which hES and iPS cells can be propagated under completely defined conditions. The establishment of such a new method would impact virtually all hES and iPS cell-based application programs as it involves a common basic process to expand undifferentiated pluripotent stem cells before turning into any type of adult cells for the therapeutic purposes. It is therefore predictable that the new methodology will be promptly translated as an intellectual property to be commercialized, and would substantially activate the biotechnology field in the State of California. More importantly, the new methodology will be provided to the Institutes in California at the highest priority where the method will accelerate the process to apply the pluripotent cell-based transplantation approach for the clinical settings that would further substantiate the enhancement of the medical environment for California citizens.
Progress Report: 
  • We have been developing new methods to identify the products of stems cells that are differentiated in tissue culture dished. We are focusing on generating a specific type of neuron - cortical interneuron. To this end, we have identified specific sequences in the human genome that drive gene expression in the immature cortical interneurons. Results from the first year of our work provide evidence that our method to use these gene expression elements is working to help us identify cortical interneurons.
  • We have identified 5 gene regulatory elements (enhancers) that can promote gene expression in a specific type of neuronal precursor and neuron. We found that these enhancers can be used to aid in the identification and isolation of these types of cells from embryonic stem cells. In other studies, our group is testing the feasibility of using these types of cells to ameliorate neurological disorders, such as epilepsy.
  • We have identified 5 gene regulatory elements (enhancers) that can promote gene expression in a specific type of neuronal precursor and neuron. We found that these enhancers can be used to aid in the identification and isolation of these types of cells from embryonic stem cells. In other studies, our group is testing the feasibility of using these types of cells to ameliorate neurological disorders.

© 2013 California Institute for Regenerative Medicine