Microbiological control in stem cell banks: approaches to standardisation

Abstract

The transplant of cells of human origin is an increasingly complex sector of medicine which entails great opportunities for the treatment of a range of diseases. Stem cell banks should assure the quality, traceability and safety of cultures for transplantation and must implement an effective programme to prevent contamination of the final product. In donors, the presence of infectious micro-organisms, like human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T cell lymphotrophic virus, should be evaluated in addition to the possibility of other new infectious agents (e.g. transmissible spongiform encephalopathies and severe acute respiratory syndrome). The introduction of the nucleic acid amplification can avoid the window period of these viral infections. Contamination from the laboratory environment can be achieved by routine screening for bacteria, fungi, yeast and mycoplasma by European pharmacopoeia tests. Fastidious micro-organisms, and an adventitious or endogenous virus, is a well-known fact that will also have to be considered for processes involving in vitro culture of stem cells. It is also a standard part of current good practice in stem cell banks to carry out routine environmental microbiological monitoring of the cleanrooms where the cell cultures and their products are prepared. The risk of viral contamination from products of animal origin, like bovine serum and mouse fibroblasts as a "feeder layer" for the development of embryonic cell lines, should also be considered. Stem cell lines should be tested for prion particles and a virus of animal origin that assure an acceptable quality.

Clinical grade adult stem cell banking

“…31 It is also required that stem cell banks maintain stringent environmental microbiological monitoring of the clean rooms where the cell cultures and their products are prepared. 141 Within the establishment, the dedicated space for quality control, change rooms, media and buffer preparation areas, with the implementation of individual hygiene plan is a must. 31 Stem cells banks should also maintain secure liquid nitrogen storage equipment with the addition of high temperature alarms in order to avoid catastrophic loss of cryopreserved cells.…”

Defined culture conditions of human embryonic stem cells

“…First, it may contain toxic proteins or immunogens that evoke an immune response and thus lead to rejection upon transplantation (17). Second, the use of animal products increases the risk of hESC contamination by the animal pathogens, such as viruses or prions (18). Third, separating animal products, such as feeder cells, from hESCs is time-and labor-intensive.…”

The way of the flesh: life, geopolitics and the weight of the future

“…Rather, these cells are part and parcel of a unique ecosystem that can contain, amongst other elements, infectious microorganisms such as human immunodeficiency virus, hepatitis B virus, hepatitis C virus and human T cell lymphotrophic virus. To be sure, screening procedures can identify these, but some newer pathogens such as transmissible spongiform encephalopathies and severe acute respiratory syndrome are almost certainly missed (Cobo et al 2005). In addition, screening can itself bring new 'contaminating' elements into play, as can the use of bovine serum and mouse fibroblasts as a feeder layer for the development of cell lines.…”