First Report from the ISCBI Coordinator, 2008

Background

Around the world, there may be in excess of 300 human embryonic stem (hES) cell lines. The status of these ranges from those of low passage (and thus unproven in experimental work) to those which have been formally prepared as large quality-controlled stocks and made available to researchers. However, many of these lines have yet to be fully characterised and formally published. Stem cell banks that are focused on making reproducible quality-controlled stocks widely available to researchers play an important role. Their job is to help sustain the availability of cell cultures which can be traced to, and still show the same characteristics as, original published cell lines as well as useful derivatives or clones. It is important to recognise that the phrase ‘stem cell bank’ can refer to a number of different levels and types of operation. This wide spectrum is illustrated in Table 2. Service culture collections can provide numerous benefits to stem cell researchers, including:

  • Release from the burden of culture, preservation and distribution.
  • Providing a safe repository of cells.
  • Making cells available to a broad range of laboratories, thus extending collaborations while retaining the depositors’ intellectual property through an appropriate agreements between the bank and its recipients.
  • Patent repository facilities (for example, those registered with the World Intellectual Property Organisation
  • Budapest Treaty (1977), see www.wipo.int/treaties/en/).

It is important that people or organisations acting at this level should be well coordinated, to help disseminate best practice, enhance international standardisation and promote the international availability of reproducible and authentic stem cell cultures. Historically, there have been numerous incidences of non-hES cell lines being switched with, or cross-contaminated by, other cell types. This has caused deleterious microbial contamination, invalidated research work and wasted investment in new cell-derived products. It is crucial that this is not repeated with hES stem cell lines, as it could delay the progress of future therapies. Well-coordinated stem cell banks could greatly reduce the impact of these issues.

Table 1 – Examples of stem cell banks and suppliers of human embryonic stem cell lines
Suppliers Web address
Bresagen www.wicell.org (http://www.bresagen.com.au or www.hospirainvestor.com)
Cellartis SA www.cellartis.com
CHIR www.mshri.on.ca/nagy
ESI www.escellinternational.com
Harvard University www.mcb.harvard.edu/melton/hues
Karolinska Institute http://ki.se/ki/ contact Dr Lars Arlund-Richter and Professor Outi Hovatti
Miz Medi Hospital www.mizmedi.com/center
Monash University www.stemcellcentre.edu.au
Reliance Life Sciences www.relbio.com
Technion – Israel Institute of Technology www.technion.ac.il
UK Stem Cell Bank www.ukstemcellbank.org.uk
WiCell www.wicell.org
Table 2 – Stem cell banks for research, production and clinical use
Type of supply of stem cell lines Primary activities
Local laboratory stocks for research
  • Satisfying demand for undifferentiated cells for experimental use
Centralised institute stocks for research
  • Provision of cultures or frozen cells to a number of laboratories
  • Basic quality control
  • Characterisation usually in individual laboratories
National supply of hES cells for a broad range of researchers
  • Establish large stocks of reproducible, well-characterised and quality-controlled cells
  • Provide safe storage as a back up for originators of lines
  • Distributed cells should meet national best practice safety guidelines (for example, screened for serious common blood-borne pathogens)
  • Operate under a published Code of Practice
  • Ensure recipients and their use of lines meet the demands of national regulations
  • Engage in other national resource and training programmes
International stem cell bank As for national banks, but with the following additional safeguards:

  • Ensure compliance of deposited lines and distribution with all national guidance, regulation and laws of depositors and recipients (ideally thorough a high level oversight body)
  • Have in place a rigorous quality assurance system that will assist in the delivery of reproducible and reliable cells and service
  • Coordination with other national banks to promote best practice
Tissue bank supplying stem cell for transplantation (for example; bone marrow, cord blood and mobilised peripheral blood stem cells)
  • Donor screening, including blood tests for viral markers
  • Fully informed consent on donated material
  • Rigorous quality assurance under national guidelines
  • Validation of bank processing procedures
  • Compliance with regulation including appropriate national or international inspections
Master and working cell banks for pharmaceutical production of medicinal products from cell lines
  • Delivery of cells for a specific end product 
  • Donor selection and informed consent if appropriate (new human cell lines)
  • Preparation under a product license in accredited cGMP facilities
  • Exhaustive accredited safety testing and quality control

Table from: Stacey, GN. Sourcing Human Embryonic Stem Cell Lines. In: Human embryonic stem cells: a practical handbook; Eds S. Sullivan, C. Cowan and K. Eggan. Wiley & Sons, in press. (www.humanEScellbook.com)

Current coordination of stem cell banks

The UK Stem Cell Bank (UKSCB) has had a variety of formal and informal contacts with scientific and government representatives from all ISCF member countries, including specific discussions on cell banking. There appears to be a general desire for greater coordination between the centres carrying out banking of stem cell lines. Some activities are already moving forward. For example, the International Society for Stem Cell Research standards committee asked the UKSCB to prepare a list of centres actively distributing hES cell lines for research. A brief summary of current stem cell banking activity is given in Table 3.

Table 3 – International activities for the establishment of stem cell banks
Country Activity
Australia Australian Stem Cell Centre supplying MEL-1 and MEL-2 hES cells for research. Discussion on plans for an Australian stem cell bank.
Canada Banking activities focused on supply of research grade cell lines primarily for Canadian researchers. Direct supply of hES cells (see Table 1).
China Number of centres with hES cell banking and requirements for clinical application under discussion incorporating regulatory authorities.
Czech Republic Supply of research grade cells (plans for Czech Tissue Engineering centre).
Denmark Propose to use UK facilities for research grade cell lines.
Finland Tissue banks being established.
Germany National coordination of hES cell groups and ongoing discussions on stem cell banking.
India Reliance Life Sciences are supplying stem cell lines and other companies are interested in supplying cells for clinical use. The National Centre for Cell Science in Pune is building a programme for 2007 incorporating a stem cell bank.
Israel Cell lines are supplied (see Table 1). A formal stem cell line bank under discussion.
Japan Bank to be established at Riken.
South Korea Research grade hES cell line available (see Table 1). Interests in establishing stem cell banks for clinical application.
Singapore ESI has been actively distributing hES cell lines (see Table 1). GMP and further research grade banking activities are under development.
Spain Granada Spanish national stem cell banking ‘node’ has activities relating to banks for clinical use and hES cell lines.
Sweden GMP cell banking work. Cellartis and the Karolinska Institute are supplying cells for research (see Table 1).
USA WiCell have been funded to run the US Stem Cell Bank of NIH registry lines. California is considering its needs for supply of research grade cells and clinical grade. ATCC has stocks of mouse embryonic stem cells and one hES cell line.