The UCLA Broad Stem Cell Research Center (BSCRC) Shared Research Laboratories (SRL) provide critical state-of-the-art FDA compliant GMP-GTP facilities for the experimental manipulation and clinical application of human pluripotent stem cells (hPSC). The SRL also includes shared hPSC laboratories and resources for intra and extra-mural investigators engaged in stem cell research. The BSCRC-SRL is not subject to federal hESC restrictions. The progress to date includes:
1. hPSC Core Banks: The creation of Core Banks for storage and distribution of hESC & iPSC to appropriately approved UCLA investigators. To date, more than 40 investigators have received cells from the Banks. The BSCRC negotiated an agreement with WiCell to locally distribute the H1 & H9 lines directly through this Bank with a streamlined process, substantially decreasing researcher time and expense to access these important lines. Over 100 vials are carried for each of our 21 hESC lines. The Banks carry genetically modified hESC lines that have new genes relevant to the work of several laboratories, 18 UCLA hESC lines on the NIH Stem Cell Registry, and 12 UCLA iPSC lines. The Banks work closely with the BSCRC Derivation Labs to establish improved protocols for generation of clinical-grade hPSC and with the ESCRO committee to ensure compliance with CA and other requirements.
2. hESC-Derivation Core Lab: This Core successfully derived 18 hESC lines under IRB/ESCRO approvals. The GMP compliant lab, with its regularly scheduled facility and equipment maintenance and monitoring, provides an essential space for deriving new high quality hESC lines that are available to the research community.
3. hESC Expansion Laboratory (EL): Supported by the BSCRC, the Lab serves as a branch of the hPSC Core Banks and is tasked with the expansion of banked hESC for distribution to qualified and approved UCLA researchers. The hESC-EL employs research technicians, establishes operating procedures for hESC culturing and distribution, derives,expands and cryopreserves sufficient quantities of mouse embryonic fibroblasts necessary for large scale hESC culturing, and distributed ~1935 hESC plates to individual researchers in CY14.
4. iPSC Derivation Core Lab: The BSCRC iPSC Derivation Core supported by the BSCRC and formerly supported by a CIRM New Cell Line award (J. Zack), facilitates clinical translation of iPSC technology by collecting & deriving fibroblasts from patients and controls under IRB and ESCRO approvals, reprogram to iPSC, and derive useful cells, all under GMP conditions. To date, the Core has derived 82 iPSC, including disease specific and control lines (Idiopathic Pulmonary Fibrosis, Duchenne Muscular Dystrophy, and other diseases). The iPSC are characterized, expanded, and deposited in the Core Bank for storage, expansion, and distribution. The Core is developing a platform from available non-integrating methods to reproducibly generate GMP grade iPSC. There are currently 3 manuscripts in preparation resulting from research in the Core.
5. Shared Resources include cell analysis (LSRII), microscopy, RTPCR, and tissue processing available to SRL users.
6. Kohn Lab: His SRL based research supports an ADA-SCID project using a lentiviral vector with 18 subjects accrued to date and all with constituted immune systems without any gene transfer related adverse events and a CIRM funded Disease Team project on stem cell gene therapy for Sickle Cell Disease (SCD). Direct adjacency of the SRL to the UCLA cGMP labs allows these GTP-level studies to be translated to GMP cell processing once clinical trial activities begin.
7. Crooks Lab: The research falls into three main areas: (a) Maintenance of and experiments with hESC lines; (b) Studies to develop implanted thymic microenvironments; and (c) Umbilical cord blood processing for use in a variety of hematopoietic stem cell experiments performed by the Crooks and Kohn Labs.
8. Martín Lab: Supported by a CIRM Tools & Technology grant, Martín develops both control and disease-specific iPSC from children and adults with various diseases, such as chronic diarrheal and other gastrointestinal and hepatic disorders that are presumably inherited.
9. Ribas Lab: The research is focused on engineered immunity of cancer in collaboration with Cal Tech investigators. Data from this project contributed to the successful CIRM Disease Team II award.