CIRM Shared Research Laboratories

CIRM Shared Research Laboratories

Funding Type: 
Shared Labs
Grant Number: 
CL1-00505-1.2
Award Value: 
$1,751,297
Stem Cell Use: 
iPS Cell
Embryonic Stem Cell
Cell Line Generation: 
iPS Cell
Status: 
Active
Public Abstract: 
Statement of Benefit to California: 
Progress Report: 

Year 1

The UCLA Broad Stem Cell Research Center (BSCRC) Shared Research Laboratories (SRL) provide 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 of each cell line are carried with 10 different unmodified hESC lines, including 6 UCLA lines on the NIH and CIRM Registries, 3 genetically modified hESC lines that carry new genes relevant to the work of several laboratories, 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 Expansion Laboratory (EL): 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 hired and trained research technicians, established operating procedures for hESC culturing and distribution, derives, expands and cryopreservers sufficient quantities of mouse embryonic fibroblasts necessary for large scale hESC culturing, and distributed ~1000 hESC plates to individual researchers. 3. iPSC Derivation Lab: Obtains human biological material for iPSC reprogramming under IRB-ESCRO approvals. The iPSC are characterized, expanded, and deposited in the Core Bank for storage, expansion, and distribution. The Derivation Lab organizes careful characterization of all generated and distributed iPSC including: karyotyping, gene expression profiling, teratoma assay, and mycoplasma testing. The Lab & Core Bank are the only UCLA facilities providing iPSC to dozens of UCLA labs yearly. The Lab developed necessary procedures to derive GMP-compliant iPSC derivatives, obtains sterile biopsies and other material that are physically and enzymatically isolated under xeno-free conditions, grown in defined media, induced to a pluripotent state with defined factors free from non-human products, expanded in defined media conditions, and then differentiated with GMP-compliant growth factors. Supported by the BSCRC and a CIRM grant, the Lab recently demonstrated that xenobiotic-free iPSC can be derived from human tissue and then differentiated providing the procedures necessary to derive GMP-compliant iPSC derivatives. 4. Shared Resources include cell sorting (LSRII), microscopy, RTPCR, and tissue processing available to SRL users. 5. Kohn Lab: The SRL based research supports a CIRM funded Disease Team project on stem cell gene therapy for Sickle Cell Disease (SCD). Data generated by this lab will be incorporated into a pre-IND application in March 2011. The investigator also defined draft eligibility criteria for SCD patients and drafted the clinical trial protocol. 6. 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. CIRM funded studies on pluripotent stem cell differentiation into mesoderm resulted in two recent papers [Evseenko et al, PNAS 2010, and Dravid et al, Molecular Therapy, 2010]. 7. Martín Lab: Tissue culture to develop 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.

Year 2

The UCLA Broad Stem Cell Research Center (BSCRC) Shared Research Laboratories (SRL) provide 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 of each cell line are carried with 10 different unmodified hESC lines, including 14 UCLA hESC lines on the NIH and CIRM Registries, 3 genetically modified hESC lines that carry new genes relevant to the work of several laboratories, and 18 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 Expansion Laboratory (EL): 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, established operating procedures for hESC culturing and distribution, derives,expands and cryopreservers sufficient quantities of mouse embryonic fibroblasts necessary for large scale hESC culturing, and distributed ~1100 hESC plates to individual researchers. 3. iPSC Derivation Lab: Obtains human biological material under IRB-ESCRO approvals for iPSC reprogramming. The iPSC are characterized, expanded, and deposited in the Core Bank for storage, expansion, and distribution. The Derivation Lab organizes careful characterization of all generated and distributed iPSC including: karyotyping, gene expression profiling, teratoma assay, and mycoplasma testing. The Lab & Core Bank are the only UCLA facilities providing iPSC to dozens of UCLA labs yearly. The Lab developed necessary procedures to derive GMP-compliant iPSC derivatives, obtain sterile biopsies and other material that are physically and enzymatically isolated under xeno-free conditions, grown in defined media, induced to a pluripotent state with defined factors free from non-human products, expanded in defined media conditions and then differentiated with GMP-compliant growth factors. Supported by the BSCRC and a CIRM grant, the Lab recently demonstrated that xenobiotic- free iPSC can be derived from human tissue and then differentiated providing the procedures necessary to derive GMP-compliant iPSC derivatives. (See: From Skin Biopsy to Neurons through a Pluripotent Intermediate Under Good Manufacturing Practice Protocols. Karumbayaram et. al., Stem Cells Trans Med, December 7, 2011; doi:10.5966/sctm.2011-0001) 4. Shared Resources include cell sorting (LSRII), microscopy, RTPCR, and tissue processing available to SRL users. 5. Kohn Lab: His SRL based research supports an ADA-SCID project and a CIRM funded Disease Team project on stem cell gene therapy for Sickle Cell Disease (SCD). Data generated by this lab was incorporated into a pre-IND conference with FDA in March 2011. 6. 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. 7. Martín Lab: A CIRM funded Tools & Technologies project to develop 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.

Year 3

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 17 hESC lines. The Banks carry genetically modified hESC lines that have new genes relevant to the work of several laboratories, 12 UCLA hESC lines on the NIH Stem Cell Registry (10 on the CIRM 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 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 ~1500 hESC plates to individual researchers in CY12. 3. iPSC Derivation Lab: The BSCRC iPSC Derivation Core supported by the BSCRC, and formerly supported by a CIRM New Cell Line award (J. Zack), obtains human biological material under IRB-ESCRO approvals for iPSC reprogramming. The iPSC are characterized, expanded, and deposited in the Core Bank for storage, expansion, and distribution. Characterization of all generated and distributed iPSC includes karyotyping, gene expression profiling, teratoma assay, and mycoplasma testing. The Lab developed and published (Stem Cells Trans Med 2011) necessary procedures to derive GMP-compliant iPSC derivatives, obtain sterile biopsies and other material that are physically and enzymatically isolated under xeno-free conditions, grown in defined media, induced to a pluripotent state with defined factors free from non-human products, expanded in defined media conditions and then differentiated with GMP-compliant growth factors. 4. Shared Resources include cell analysis (LSRII), microscopy, RTPCR, and tissue processing available to SRL users. 5. Kohn Lab: His SRL based research supports an ADA-SCID project 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. Kohn also used the SRL for pre-clinical studies of cell processing for a new trial he will open in 2013 on gene therapy for ADA-deficient SCID using a lentiviral vector. 6. 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. 7. 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. 8. 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.

Year 4

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, 12 UCLA hESC lines on the NIH Stem Cell Registry (with 6 pending), 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 ~1740 hESC plates to individual researchers in CY13. 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 57 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 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. Kohn also used the SRL for pre-clinical studies of cell processing for a new trial he will open in 2013 on gene therapy for ADA-deficient SCID using a lentiviral vector. 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.

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