ReGenesys BVBA is an early stage biotechnology company based in Heverlee (Leuven), Belgium. ReGenesys is a wholly owned subsidiary of Athersys, Inc, a publically traded US based biotechnology company. ReGenesys was established as a research unit for development of new stem cell isolation and expansion technologies, and to support cell therapy clinical studies in Europe. Athersys has developed a stem cell therapeutics platform and is in Phase I clinical testing for use of the cells in treatment of acute myocardial infarct, ischemic stroke, and as an adjunct in allogeneic bone marrow transplant.
It is our desire to globally commercialize an adherent adult stem cell product produced using animal product-free conditions. While addressing the important aspect of patient safety, this achievement would also establish an important competitive regulatory threshold for our product. Our requirements are to identify and clinically manufacture cell products using serum-free media prior to initiating pivotal Phase III clinical studies. Our current target for development and testing of a serum-free media formulation is early 2012, based on progress in our ongoing clinical trials.
We have developed a human stem cell platform (MultiStem®) that has been approved by the FDA for use in phase I clinical trials. This platform is based on the discovery of a rare cell type (Multipotent Adult Progenitor Cells; MAPC) by Catherine Verfaillie and co-workers that was subsequently patented (US Patent 7,015,037 B1) and then licensed by Athersys. MultiStem® is an adherent stem cell derived from bone marrow that has developmental potential greater than the limited mesenchymal lineage capacity of mesenchymal stromal cells (MSC). MultiStem® thus constitutes the large-scale expanded form of human MAPC. ReGenesys is currently expanding manufacturing and clinical development in Europe. Our current understanding is that we will need to modify our platform towards animal product-free manufacturing for reasons of safety and traceability (EC directive 04 May 2005). Serum and other compounds of animal origin vary from batch to batch despite the enormous care that is taken during their isolation and production, and may carry adventitious pathogens.
Stem cell biology is still in an early phase of development. For instance, the insight in the behaviour of rare adult stem cells during culture is poor. Pluripotent stem cells are defined as exhibiting differentiation towards cells of each primitive germ layer; mesoderm, ectoderm, and endoderm. The mitogenic stimulation required to expand these populations also results in maturation of their developmental profile, and indeed, long term cultures are difficult to maintain and are frequently primarily composed of cells showing only mesodermal differentiation potential. Moreover, stable cultures only seem possible if cell density is kept under a certain 'trigger' value, different for every species MAPC have been isolated from. This implies that the developmental profile of these cells is regulated by depletion of key media components, by accumulation of metabolites, paracrine factors or combinations of these.
A proteomics approach would be most suitable to address this complicated analysis. But, the use of foetal bovine serum (FBS) in (stem) cell media formulations complicates proteomic analysis due to high levels of bovine serum albumin (BSA) and other proteins (e.g. immunoglobulins). The interpretation of screening results could also be hampered due to variability in serum lots. However, a significant practical impediment to a proteomic screening strategy is exactly the lack of a chemically defined medium for our cells. The fundamental proteomic biology of these cells cannot be studied in the absence of media formulation enabling analysis of key components.