Generation of human embryonic stem cell lines, under defined conditions, modeling normal & diseased states from material stored at the {REDACTED} embryo bank

Funding Type: 
New Cell Lines
Grant Number: 
RL1-00675
Investigator: 
ICOC Funds Committed: 
$0
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, {REDACTED} is designed to serve the research community at no cost. With numerous layers of ethical, medical, & 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). We propose to generate a library of well-defined hESC lines that authentically model the range of diseases one can diagnose in the embryo & that would compel them to be rejected for implantation. Although unethical to implant, these blastocysts could yield hESCs that might ultimately inform us of the mechanisms underlying incurable human diseases & perhaps point the way towards new therapies. Indeed, the lines could be used to screen for new drugs & diagnostics. Few teams are as well equipped as we to pursue these critical proof-of-concept experiments while providing a valuable resource for scientists. In addition, {REDACTED}, which, as an academic non-profit embryo bank providing a service to scientists & families without encumbrances, requires CIRM financial support to stay active.
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 intellectual property (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. Also, California citizens should become stakeholders in the IP & benefit from any royalties & fees.

© 2013 California Institute for Regenerative Medicine