Isolation of Human Lymphoid Progenitors and Induction to the B and T Cell Fates

Funding Type: 
SEED Grant
Grant Number: 
RS1-00262
ICOC Funds Committed: 
$0
Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 
The immune system is the body’s first line of defense against pathogens. Immune system cells develop from the fetal liver during embryonic development and then in the bone marrow in adults. Fetal liver and bone marrow stem cells can develop into all of the types of immune system cells. T cells and B cells, two components of the immune system, are important for the control of the immune response against bacteria and viruses, and provide the “memory” of the immune response against same pathogen upon re-infection. As such, healthy T and B cells are crucial to the overall health of the individual. Patients with genetic deficiencies in T cells and B cells often have severe infections and limitations that require lifelong drug treatments. Some immune deficiencies and leukemias can be cured with bone marrow transplantation, but this requires finding a specific matched donor, sometimes impossible to find. Regenerative medicine, which utilizes embryonic stem cells as a primary source of cells, could be an alternative therapeutic approach for these diseases. However, basic information on the biology of embryonic stem cells and the signals which influence their development into specific cell types is needed before regenerative medicine is a reality. The aim of this research proposal is to understand the process by which hESC develop into blood cells, with a particular emphasis on the development of T cells and B cells. We hope to identify cells at specific stages of blood cell development based on the proteins they express on their surface and isolate the stages that are most likely to develop into T and B cells. We will then optimize the culture conditions so that human T and B cells can be efficiently and reliably derived from human embryonic stem cells and used in regenerative therapies for immune deficiencies and cancer.
Statement of Benefit to California: 
The research proposed could benefit the State of California and its citizens at several levels. Higher education would be supported by hESC research, as university students seek training and education to allow them to enter this field. The types of degrees earned would not necessarily be limited to biology and health, but could also include economics and sociology to examine the fiscal impact and social impact of hESC research on the state. Health could be improved using regenerative medical therapies aimed at immune system development. Development of protocols to derive lymphocytes reliably from hESC could attract industry and biotechnology companies to the state, an economic benefit both in terms of monetary gain as well as in creation of jobs. All of these benefits, in turn, will attract international attention and recognition to the State of California for being at the forefront of hESC research.
Progress Report: 
  • The grant investigates to grow human neural progenitor cells by manipulating Ryk-mediated Wnt signaling. We discovered that Ryk signaling regulates neurogenesis and cleavage of Ryk is important for this processes.
  • Neurodegenerative diseases such as Alzheimer’s and Parkinson, as well as neuronal injuries caused by stroke or trauma, result in neuronal cell loss. Current treatments cannot replace or repair the damaged cells. Our proposed research may ultimately lead to the development of an effective treatment for neuronal cell loss.
  • We have set up an effective system for growing neural progenitor cells derived from human ES cells. We have performed experiments aimed at expanding neural stem cell populations and growing neurons. This could lead to many possible clinical applications.
  • Transplant-ready neuronal tissues, gene therapies, and drugs targeting the Wnt pathway in order to promote neuronal regeneration are some of the treatments for neurological disorders that may be possible in the future. Our findings will facilitate the progress of developing these new, promising treatments. The success of our project in neural progenitor cell expansion could greatly improve the quality of life for Californians and people everywhere.

© 2013 California Institute for Regenerative Medicine