National Institute for Biological Standards and ControlAssuring the quality of biological medicines

Bank Update II: focusing on contributions to R&D

Lyn Healy, UK Stem Cell Bank

UKSCN, Nottingham, July 2010

The UKSCB

The UKSCB prepares and supplies worldwide, well characterised seed

stocks of ethically sourced human wild type and disease-specific adult,

foetal and embryonic stem cell lines.

All cell lines are banked within a stringent quality framework.

All activities comply with the UK Code of Practice

for the use of human Stem Cell Lines.

Principles of theUKSCB

UKSCB according to the following principles:• Transparency (SC, UKSCB Code of Practice)• Disseminate best practice/information• Future proofing – anticipate new demands

(please fill in our survey)• No charge to depositors for banking/quality

control• Currently no charge for supply (shipment only)• No conflicts of interest in basic stem cell

research or commercial development

However:• The bank can be involved as a collaborator in basic

research by providing services.• The bank can be involved in assay development.• The bank can perform research in areas to standardise

the banking process.• The bank can be involved in research to better

characterise stem cells• The bank can be involved in projects that enhance the

quality of the product.

No conflicts of interest in basic stem cell research or commercial development

Release criteria for the cell banks

Basic criteria:

• Viability• Sterility• Identity• Genetic stability

Why characterise the banks?

• Correct phenotypic and function– Surface markers, RNA, differentiation/ pluripotency

• Correct identity– DNA profile

• Absence of microbial contamination– no fungi,bacteria,yeasts viruses and mycoplasma

• Stability of in vitro cultures:– Passage – Culture conditions

Could effect outcome of future studies and data interpretation

hESC line: abnormal karyotype

ISCI

Characterisation Adds Value to the Cell Lines Assures Quality

The Stem cell Community and the Bank

Stem cell community has been fundamental in helping the bank to operate efficiently and effectively:

• Training provided through Peter Andrews and Harry Moore’s groups

• Involvement In the ISCF projects: ISCI projects as a hub lab providing reagents and testing ISCBI project as the co-ordinators• Numerous interactions with national and international

collaborators• Provided insight into areas where standardisation science

can be applied.

HighlightedCurrent In House Projects

Feeder Study• Support and expansion of a selected number of hESC lines• A range of mouse and human feeders (looking at manual and enzymatic passaging)

.• Characterising the cells over 20 passages. (Poster number 65)

Novel surfaces study in collaboration with Orla Development of low resolution CGH• Adjunct to traditional G-banding• Genetic stability• Whole population dynamics• Level of sensitivity

HighlightedCurrent In House Projects

Quantitative Imaging for the quality control of Cell Banks :• Looking single assay to replace two QC assays. Flow cytometry for a quantitative measure of cell surface

markers and in situ staining for a spatial anaysis of expression in cultures

• Validation of system• Exploring other uses in the area of differentiation. • Tool-up exercise for future projects

TissueFAX

Flourescence and brightfield capabilitiesSoftware packages TissueQuest and HistoFax

My main project

Development of a rapid testing method for viral targets using real time PCR in a low density array format. Collaboration with LifeTechnogies (Applied Biosystems), Rutgers University, US., Division of Virology, NIBSC and the UKSCB

TLDA Viral Cards

• Simple to use microfluidics card.

• Validate microarray hits quickly and economically

• Standardise screening of viral gene targets across multiple samples

• Can load 384 wells in less than five minutes without liquid-handling robots or multi-channel pipettors

Currently.....

• Targets have been validated using artificial templates and bona fide viruses

• Confirming that there is no cross reactivity between targets• Looking at assessing copy number against the

international standards (at NIBSC) for viruses• Card is being tested by other interested research groups

Next Challenges

Extension of banking activities: 2 new posts

• Differentiation of pluripotent cell lines: To further characterise the lines and provide further

information to the Stem cell community.

• Scale-up and Automation: Towards clinical translation activities