Stem cell culture is another emerging small culture technique with a potentially large impact. According to COO Hugh Ilyine of Stem Cell Sciences (SCS; www.stemcellsciences.com), the supply of stem cells is the critical component of this business.
Established stem cell techniques harvest cells from animal or cadaver tissues. More exciting are recent developments that collect stem cells from a variety of human tissues for example bone marrow and embryo-related tissue. These sources will eventually provide stem cell researchers with a wide variety of cells in a reliable, predictable format, which is expected to lead to commercialization of therapeutic stem cells.
SCS focuses on the production side of stem cells, which means fully defined media products to grow and control stem cell biomass, and to induce differentiation. The company is currently scaling up its technologies for growing cells, including media, at its new facility in Cambridge, U.K.
Within SCS’ SC Proven line of media products are the PassAID™ medium supplement and the HEScGRO™ medium for human embryonic stem cell culture. PassAID is a media supplement containing a Rho-associated kinase inhibitor for the enzymatic passaging of human embryonic stem cells. HEScGRO medium is claimed to be the first human embryonic stem cell growth medium that is complete, serum-free, animal-component free, and ready to use.
Also offered are ESGRO Complete™ clonal-grade medium that enables mouse stem cells to grow in the absence of fetal bovine serum or primary mouse fibroblast feeder cells and NDiff™ Neuro medium supplements for in vivo differentiation of murine embryonic stem cells. All of the SCS’ media products are available through Millipore (www.millipore.com).
In addition to media and nutrients, SCS licenses its stem cell production, selection, and genetic engineering technologies to research and commercial organizations. Among its licensees are Merck, to which SCS also sells media for growing and differentiating cells.
BrainStorm Cell Therapeutics’ (BCT; www.brainstorm-cell.com) principal business is to treat neurodegenerative diseases through autologous reimplantation of adult stem cells. Because the cells are harvested from the eventual patient, BrainStorm sidesteps not only the ethical issues related to embryonic stem cells, but the potential for tumorigenicity from heterologous transplants.
Using a procedure developed at Tel Aviv University by Eldad Melamed, M.D., Brainstorm scientists harvest mesenchymal stem cells from the bone marrow cells from patients, propagate them to create a large mass of cells, then differentiate them into the desired neurological cell types. Mesenchymal cells are notable for their dual ability to create identical daughter cells or turn into somatic cells. For neurodegenerative disease treatment that means specialized neuron-like cells that release dopamine and glial-derived neurothrophic factor.
The company is targeting Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis. It has developed an animal model of Parkinson’s in which implanted nerve cells can cure or delay the onset of disease. BCT is now looking to turn the process into a robust, reproducible protocol suitable for human testing.
Embryonic stem cells grow easily, as do those taken from fetal tissues. Adult stem cells, currently a hot area of research, are more difficult to propagate. BCT puts a lot of effort into growing adult stem cells in large quantities, according to Avinoam Kadouri, Ph.D., chief technology adviser. “The problem,” says Dr. Kadouri, “is the low native abundance of highly desirable mesenchymal and progenitor cells.”
The breakthrough for BCT was a protein-containing media that is animal-derived component-free. Dr. Kadouri describes the media as the significant factor that allows propagation of stem cells without differentiation. Once the cell mass is large enough, the cells are allowed to differentiate into dopamine-secreting astrocytes (for neurodegenerative diseases), or bone, fat, or other cells. The mixture of added growth factors and cytokines dictates what direction the cells take.
Getting really small with cell culture is useful for research, particularly for ADME, toxicology, drug discovery, cell line engineering, media optimization, as well as for monitoring the health of a large culture. Nikon Instruments (www.nikoninstruments.com) recently introduced a microscope product, the BioStation CT, that allows users with minimal microscopy experience to conduct imaging of live cells locally or by remote operation over a computer network. BioStation CT allows investigators to manage, observe, and record vital cell characteristics (growth, morphology, protein expression) from multiple cultures under environmentally controlled conditions.
The microscope can also measure multiple parameters within cells through user-selected settings for magnification, fluorescence wavelengths, viewing axes and dimensions, and multiple fluorescence modes.