Critical to the long term success of the CIRM iPSC Initiative of generating and ensuring the availability of high quality disease-specific human IPSC lines is the establishment and successful operation of a biorepository with proven methods for quality control, safe storage and capabilities for worldwide distribution of high quality, highly-characterized iPSCs. Specifically the biorepository will be responsible for receipt, expansion, quality characterization, safe storage and distribution of human pluripotent stem cells generated by the CIRM stem cell initiative. This biobanking resource will ensure the availability of the highest quality hiPSC resources for researchers to use in disease modeling, target discovery and drug discovery and development for prevalent, genetically complex diseases.
The generation of induced pluripotent stem cells (iPSCs) from patients and subsequently, the ability to differentiate these iPSCs into disease-relevant cell types holds great promise in facilitating the “disease-in-a-dish” approach for studying our understanding of the pathological mechanisms of human disease. iPSCs have already proven to be a useful model for several monogenic diseases such as Parkinson’s, Fragile X Syndrome, Schizophrenia, Spinal Muscular Atrophy, and inherited metabolic diseases such as 1-antitrypsin deficiency, familial hypercholesterolemia, and glycogen storage disease. In addition, the differentiated cells obtained from iPSCs represent a renewable, disease-relevant cell model for high-throughput drug screening and toxicology/safety assessment which will ultimately lead to the successful development of new therapeutic agents. iPSCs also hold great hope for advancing the use of live cells as therapies for correcting the physiological manifestations caused by disease or injury.
The applicant proposes the establishment of a repository for the banking and distribution of human induced pluripotent stem cell (hiPSC) lines from 3000 tissue donors as well as 300 additional human pluripotent cell lines from California investigators. This derivation proposal was submitted as a collaborative effort with RFA 12-03 hPSC Derivation Awards proposal ID1-06557. The proposed facility will implement a fully integrated and comprehensive tracking process for shipping of donor tissue, isolation of primary cells, iPSC derivation, cell line expansion and quality characterization, safe storage inventory and distribution. Plans for re-expansion of cell lines and extensive quality assessment of expanded iPSC clones are described. The applicant will build on established procedures and collaborative relationships to rapidly set up the facility and ensure its sustainability.
Quality of the Proposed Repository
-Well-developed banking procedures, carefully defined set-up plans and extensive experience in cell banking ensure the high quality of the proposed repository.
-Reviewers appreciated the well-established system for tracking banked cells and tissues.
-The ability to handle primary samples of different tissue types (e.g. blood and skin) was viewed as a significant strength.
-Reviewers felt that the management plan was well designed and featured an appropriate layer of oversight to ensure quality.
- Proposed sustainability plan for the repository was considered a strength of this application.
-Reviewers were confident that the proposed facility could handle completely the 3000 tissue samples and derived cell lines.
-Plans to establish and expand the repository were considered reasonable and sound.
-Interactions and plans for coordination with a potential deriver were well developed, but reviewers expressed concern about whether some components of the proposal would need to be altered and feasibility lessened if a different deriver is selected.
Program Director (PD) and Team
-The PD and team are excellent and have a great depth of experience and extensive expertise in cell banking.
-Reviewers expressed some concern about the need to hire and train new personnel for establishment of the facility in California, and exact staffing needs were unclear.
Appropriateness of Budget
-Overall, the budget appeared to be appropriate.
-Some concerns were expressed about subcontracts for cell expansion and quality assessment; it was unclear that costs/expenditures would be tied appropriately to the number of cell lines processed. CIRM should ensure that payments ultimately reflect the actual number of hiPSC lines expanded for a given budget year.
- Derek J Hei