The cornerstone of the Sue and Bill Gross Stem Cell Research Center will be a state-of-the art research and clinical building that will foster a multi-pronged approach to neurodegenerative repair and basic stem cell biology by supporting basic research, regenerative medicine and drug-development programs. Building facilities will include a Stem Cell Core Facility for production and characterization of new stem cell lines including advanced cell culture; microscopy and cell sorting capabilities; a vivarium for animal experimentation and care; and an outpatient clinical facility for development of clinical outcome measures and safety/efficacy testing of therapeutics.

The Stem Cell facility will be the fourth building in UCI's Biomedical Research Center, a complex that houses the Reeve-Irvine Research Center, the Institute for Brain Aging and Dementia and the General Clinical Research Center. The Stem Cell Facility is planned as a 52,300 square foot, four-story building that is the mirror image of the General Clinical Research Center. Given that the land and building plans are ready, the facility will be on-line within 20 months of construction commencement.

The Facility will house approximately 15 principal researchers and their teams, and is designed to efficiently accommodate changes in Stem Cell Research Center programs over time. Lab and office space will be available for visiting scientists, as collaborations will likely be critical to this research. In addition to these scientists, many more will have access to the resources in the Stem Cell Building through the Stem Cell Core Facility. The Core supports all aspects of stem cell research from development of new lines to high-through put differentiation and sorting platforms to animal model testing of potential therapies.

The Stem Cell Facility Programs

The Stem Cell Facility will support several major research programs that seek to better understand how stem cells work, what they can be used for, and generate therapies for a multitude of diseases and disorders.

The Basic Research Program explores methods to improve the isolation of embryonic stem cell lines and to modify them genetically by nuclear replacement and targeted mutagenesis.

Program experiments will include:

• Controlling mitochondrial as well as nuclear genotype in stem cells. It is possible that genetic manipulations could be used to tailor stem cells to prospective patients, both to avoid immune rejection and to correct genetic deficiencies. UCI is unique in having both the genetic and stem cell expertise to address this issue.
• Understanding the molecular and genetic mechanisms as well as the environmental conditions that maintain the stem-cell phenotype and that control the differentiation of stem cells into different tissue types. The importance of the stem-cell environment will be investigated by testing the effects of artificial and natural three-dimensional supports in vivo and in vitro.
• Research from the biomedical engineering perspective, using microfluidic, chip-based and encapsulation methods for the characterization, control, sorting and delivery of stem cells.

The Drug Discovery Program operates at two levels: it supports in vitro stem cell-based screens to identify novel drugs targeting cell proliferation, differentiation and death; and it supports studies of the pharmacological impact of these agents in vivo using relevant animal models of disease. Chemical libraries created through internal efforts (e.g., by structure-based design coupled with focused library synthesis) or obtained from external public or private sources (for example, the NIH chemical genomics initiative) will be screened for their ability to influence proliferation, differentiation and survival of genetically modified human stem-cell lines that target specific disease conditions - such as, one in which a relevant transcription factor is linked to a readily measurable physico-chemical response. Compounds that successfully pass the first screen will undergo optimization by successive in vitro and in vivo steps aimed at increasing potency, target selectivity, bioavailability and in vivo activity. The ultimate aim of this process is to generate viable drug candidates for clinical testing.

The Therapeutic Development and Application Program supports research into the efficacy and safety of stem cell or drug-based therapies, and their clinical translation. This Program involves the use and development of animal models and outcome measures of brain and spinal cord injury, stroke, demyelinating diseases including multiple sclerosis, and neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, and Parkinson's disease. Another major target will be both juvenile and adult diabetes. Translation of animal research to the clinic will be facilitated by the SCRC Outpatient Clinical Facility, and partner institutions including the Joslin Diabetes Center at UCI, UCI Medical Center, the University Children's Hospital, Children's Hospital of Orange County and Long Beach VA Hospital, for the development of clinical outcome measures and safety/efficacy testing of cell-based treatments. All activities within this Program, from basic research through to clinical application, will be conducted in compliance with FDA guidelines under the oversight of an in-house Regulatory Quality Assurance Officer in order to expedite clinical and commercial translation.