Generation of hESC lines, under defined conditions, modeling normal & diseased states from material stored at the Burnham shared embryo bank.

Funding Type: 
SEED Grant
Grant Number: 
RS1-00305
Investigator: 
ICOC Funds Committed: 
$0
oldStatus: 
Closed
Public Abstract: 
The human embryonic stem cell (hESC) lines eligible for federally-funding are limited not only in number but also in their: (a) range of applications (e.g., because of their “contamination” with poorly-defined biological components); (b) genetic & cell type stability; (c) ability to represent diverse racial & genetic backgrounds, disease states, & heritable predispositions to disease; (d) ease of manipulation, expansion, differentiation; (e) safety. The field would benefit from new hESC lines that not only reflect newly emerging biological insights but that improve upon extant lines in the following 3 key areas: (1) hESC lines derived from their inception under “defined” conditions (i.e., conditions where all ingredients can be specified); (2) hESCs that can serve as models for a range of human diseases (particularly those for which poor animal models exist) which would allow the development of better therapies, including drug development; (3) hESCs that can be more facilely maintained under defined conditions in the immature state & then efficiently & reproducibly become desired cell types to the exclusion of undesired cell types. To help meet these needs, we have established a repository for normal & abnormal preimplantation embryos donated from IVF clinics nationwide for research purposes. This non-profit facility is designed to serve the research community at no cost. With numerous layers of ethical & financial oversight in place, we have already catalogued ~1000 normal & disease-bearing blastocysts. Our Stem Cell Research Center has devised improved techniques for deriving & differentiating hESCs. One of these advances was the establishment of an efficient long-term defined culture system for hESCs that is based on having determined the minimal essential components for insuring pluripotency & exploits intrinsic embryogenesis-like processes. These techniques have been used to begin deriving hESC lines from normal & diseased blastocysts (identified by pre-implantation genetic diagnosis [PGD]). The repository, because it has access to IVF services, is also staffed by an embryologist with extensive experience in nuclear transfer (NT), i.e., transfering the nuclei from skins cells into unfertilized eggs in large animals. We also maintain skin cell cultures from patients with genetic defects, the best characterized of which is called Lesch-Nyhan disease (LND). In the spirit of the Seed Grants, we propose to combine all of our skills & resources to generate well-defined disease lines not only from PGD but also by NT – as proof of concept & validation of the approach. In the course of pursuing these goals, we will also generate needed normal hESC lines. Few teams in CA are as well equipped as we to explore these critical yet admittedly high risk proof-of-concept experiments.
Statement of Benefit to California: 
The human embryonic stem cell (hESC) lines eligible for federally-funded research are limited not only in number but also in their: (a) range of applications (e.g., because of their “contamination” with poorly-defined biological components); (b) genetic & cell type stability; (c) ability to represent diverse racial & genetic backgrounds, disease states, & heritable predispositions to disease; (d) ease of manipulation, expansion, differentiation; (e) safety. The field would benefit from new hESC lines that not only reflect newly emerging biological insights but that improve upon extant lines in the following 3 key areas: (1) hESC lines derived from their inception under “defined” conditions (i.e., conditions where all ingredients can be specified); (2) hESCs that can serve as models for a range of human diseases (particularly those for which poor animal models exist) which would allow the development of better therapies, including drug-based; (3) hESCs that can be more facilely maintained under defined conditions in the immature state & then efficiently & reproducibly become desired cell types to the exclusion of undesired cell types for research & cell-based therapies. To help meet these needs, we have established a repository for normal & abnormal preimplantation embryos donated from IVF clinics nationwide for research purposes. This non-profit facility is designed to serve the research community – particularly in California-- at no cost. We have also devised improved techniques for deriving & differentiating hESCs. These techniques have been used to begin deriving hESC lines from normal & diseased blastocysts. These new lines, too, become invaluable unique reagents for drug testing, for testing the pathophysiological mechanisms underlying a wide variety of disease states, & for developmental studies. Federal funding cannot presently be used to generate such new lines. Lines generated with industrial funds would inevitably carry large licensing fees & restrictions on the use & dissemination of IP & insights derived from such studies. Our intent is that such reagents be distributed in an unencumbered manner to other investigators who would be obligated to share data with other scientists, & that the products of that research (drugs, therapies, diagnostics, technologies) be made available at minimal cost to California citizens.

© 2013 California Institute for Regenerative Medicine