CIRM FAQs
What is the CIRM iPSC Repository?
The CIRM iPSC Repository is a biobank of human induced pluripotent stem cells (iPSCs) containing one line from each of approximately 2,500 individuals, 80% of which come from donors with clinical manifestations of Lung, Liver, Eye, Heart, or Neurological disorders (including developmental disorders and Alzheimer’s disease) and remaining from healthy donors. The donors were selected by leading California researchers who proceeded to then collect a sample from each participant. These donor samples were converted into iPSC lines by FUJIFILM Cellular Dynamics, Inc. (FCDI), using its proprietary episomal reprogramming method that does not introduce exogenous DNA into the lines. The CIRM iPSC Repository is maintained and administered by FCDI, which includes the storing and distributing de-identified donor clinical information associated with the CIRM iPSC Repository samples.
How can I order a sample from the CIRM iPSC Repository?
Every requester must execute a non-negotiable, Material Transfer Agreement, which can be downloaded from the ordering webpage. All commercial entities, as well as academics or non-profits engaged in commercial activities, must take a license using the Standard License Agreement for the CIRM iPSC Repository. Commercial activity by an academic or non-profit entity is defined as fee-for-service or sponsored research or other arrangements in which another party has rights to the output of the work performed
What are the fees for access to the iPSC lines?
Academic and non-profits, not engaged in commercial activities, pay a fee of $750 per vial. Commercial fees are $1,500 per vial in addition to the fees as outlined in the Standard License Agreement. Licensees are required to pay annual renewal fees to maintain their license. Failure to renew a license will require immediate destruction of all CIRM iPSC lines and derivatives as stated in the license.
If I need a Standard License Agreement, what do I need to do?
There are two licenses available depending on the number of employees in your organization.
Standard License Agreement (Small entity; <100 employees)
Standard License Agreement (Large entity; >100 employees)
To obtain a license, download the Standard License Agreement for the CIRM iPSC Repository appropriate for the size of your organization. The license must be signed by a duly authorized person in your organization and sent to FCDI-licensing@fujifilm.com for countersignature. After your payment for the license invoice is received by FCDI, your company’s license will be active, and you can proceed with ordering.
Are the license fees for a single iPSC line or for all the lines in the repository?
The Standard License Agreement for the CIRM iPSC Repository covers all the iPSC lines in the bank. The license fees are not per line but for the entire bank.
If my organization has a license from iPS Academia Japan (iPS AJ), are my fees for the CIRM license reduced?
iPS AJ has informed FCDI that, as of August 2015, no entity has a license from iPS AJ that is as broad for research use as the license rights available here. If any organization with an existing license from iPS AJ wishes to explore whether any credits may be applied to the CIRM Standard License Agreement Fee, they must contact iPS AJ. Further, the organization should request iPS AJ to notify FCDI at FCDI-licensing@fujifilm.com that the organization has an active iPS AJ license and the amount of the fee discount, if applicable.
What information is included in the donor consent?
Donor's consent included statements regarding:
- Genomic analysis and genomic data dissemination to other researchers
- Changing the genetic code within these cells (i.e., genetic engineering)
- Using cells to test or select drugs to treat disease
- Transplanting cells or resulting products in animals
- Distributing cells widely, both nationally and internationally, for research, training, or commercial medical product development
- Future research and uses unforeseen at this time
All donor consent forms followed guidelines set by CIRM and were approved by Institutional Review Boards (IRBs). All the materials were collected under IRB from the Institutions that collected the material.
What information is included in genomic analysis and genomic data dissemination to other researchers?
All tissue collectors completed a CIRM iPSC Repository Data Use Limitation (DUL) Record.
DUL records are available for CIRM iPSC collections. Primary permissible use of Data includes General Research Use. Data can be used for research, training and the development of medical or commercial products. Both controlled-access and open-access are permitted.
How were the samples reprogrammed?
All lines in the CIRM iPSC Repository are created by the same standardized procedure in a single production facility operated by FCDI to minimize lab to lab variability. The samples are reprogrammed by FCDI’s proprietary methods employing non-integrating episomal vectors.
What testing is performed on the samples?
Donors were screened for infectious diseases including Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), and Hepatitis C (HCV). Donors under the age of 18 could opt out of HIV testing; all HCV-positive donors submitted skin punches, not peripheral blood, and were not screened for any infectious agents due to small volume of blood present in punches.
Additionally, each line undergoes quality control testing that includes:
| Chromosomal Integrity | SNP microarray (Illumina Infinium HumanCore BreadChip). | No deletions of amplifications larger than 5MB (resolution of traditional G-branding assay) on SNP arrays with LogRDev score less than 0.5. Donor DNA is tested on all abnormal clones to whether the genetic abnormality is due to in vitro culture or is pre-existing in the donor. If the abnormality is pre-existing in donor, the iPSC line is released to Repository. |
| Pluripotency | Analysis of gene expression by qPCR of 48 mRNAs. | A non-probabilistic binary linear classifier identifies the gene expression of the sample as iPSC based on an appropriate training set. This method has been benchmarked against traditional teratoma assays. |
| Identity Confirmation | Genotyping using PCR assay for 48 SNPs. | ≤ 1 mismatch between donor and iPSC line |
| Loss of Reprogramming Transgenes | Endpoint multiplex PCR for two plasmid sequences (EBNA and OriP). | Detection of ≤ plasmid copy per 100 cells or a decrease in the number of plasmid copies detected at passage 5. |
| Mycoplasma | qPCR for 8 species. | Negative for all 8 species |
| Sterility | Microbiological testing by third-party service provider. | Negative for all tests |
How were the iPSC lines cultured and cryopreserved?
All lines are grown using Essential 8 Medium and vitronectin (VTN-N) and cryopreserved in colony form.
Is there genomic sequencing or genotype confirmation of mutations in the diseased lines available?
Analysis of omics data was not part of the original CIRM iPSC repository construction. Subsequently, several grant-supported efforts have collected and deposited omics data from certain CIRM collections into multiple genomic databases. These data include SNP data for 2166 CIRM lines and whole genome sequence (WGS) data for 299 of the CIRM iPSC donors and can be found at dbGAP and AnVIL. A list of the CIRM lines with WGS data can be found here.
If I want to publish my research using the CIRM cell lines, what are the guidelines?
Any public dissemination, whether written publication or oral presentation, of data or results generated from the use of Materials, Modified Materials, Unmodified Materials and Differentiated Cells must cite the CIRM Repository catalog identification number(s). "The following cell lines were obtained from the CIRM hPSC Repository funded by the California Institute of Regenerative Medicine (CIRM) [list Repository ID numbers here]."
