ReGenesys is a biotechnology company based in Heverlee (Leuven), Belgium. ReGenesys is an affiliate of Athersys, Inc (ATHX, NASDAQ). Athersys is focused primarily in the field of regenerative medicine. It is committed to the discovery and development of best-in-class therapies designed to extend and enhance the quality of human life. 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 (MultiStem®) that is based on the discovery of a rare cell type (Multipotent Adult Progenitor Cells; MAPC) by Catherine Verfaillie and co-workers. MultiStem is thus an adherent stem cell derived from bone marrow that has developmental potential greater than the limited mesenchymal lineage capacity of mesenchymal stromal cells (MSC). ReGenesys is continuing as the R&D hub of the company and preparing for a global impact of the cell therapies the company is developing. ReGenesys is assisting with the transition of process development towards manufacturing but at the same time developing a pipeline of new products and formulations.
MultiStem cells are in Phase II clinical testing for use in treatment of a number of diseases (ulcerative colitis, acute myocardial infarction and ischemic stroke). Safety studies (Phase I clinical trials) using MultiStem as an adjunct in allogeneic bone marrow transplantation for prevention of GvHD and AMI have been completed. Pre-clinical animal studies have also clearly shown therapeutic benefits of MultiStem cells in cardiovascular and neurological disorders such as traumatic brain injury, spinal cord injury and ischemic limb injury. The therapeutic benefits of MAPC are multimodulatory and have been shown to be caused by their pro-angiogenic effect through trophic support and their ability to modulate the immune system.
Xeno-free MAPC cells
ReGenesys has a strong focus on the development of a xenobiotic-free stem cell product. We have developed a complete xenobiotic-free workflow for the isolation, expansion and cryopreservation of MAPC cells (XF-MAPC). We identified different serum-free media in which cells could be expanded and subsequently conditions were identified that allowed xeno-free isolation of MAPC cells from bone marrow. We also showed that XF-MAPC can be cryopreserved in a DMSO-free and serum-free formulation. Xeno-free MAPC isolation from bone marrow and subsequent expansion shows linear growth kinetics up to the number of population doublings that are required to obtain clinical MultiStem doses. Extensive cell comparability testing revealed that the xeno-free cells retain MAPC/MultiStem characteristics, including marker expression (protein, mRNA, miRNA), high telomerase activity, differentiation capacity, in vitro pro-angiogenic and immunosuppressive activity, and genomic stability.
Cell comparability testing platform and integrative omics analysis
The development of a xeno-free cell product required extensive cell comparability testing. During the testing of xeno-free expansion, we have strongly focused on optimizing a cell comparability testing platform. This includes identity testing (e.g. marker expression, telomerase activity), biological activity (differentiation, angiogenic activity, immunosuppression) but also ‘omics’-based screens. In particular the omics based screens have been strongly developed during the last few years and we have obtained extensive datasets on MAPC and XF-MAPC based on mRNA profiling, DNA methylation, Next Generation Sequencing-RNA and miRNA.
ReGenesys cell comparability testing platform