In contrast to other stem cell types that have been described, MultiStem cells exhibit four important characteristics.
First, in contrast to more specialized stem cell types that can only form a limited number of cells or tissues, MultiStem cells have remarkable biological plasticity, and can give rise to a broad range of cells and tissues. MultiStem cells have been shown to differentiate into the major cell types and tissues in the body - including cells from each of the primary germ layers, which comprise the inner (endoderm), middle (mesoderm), and outer (ectoderm) tissue layers of an adult, which makes them unique among non-embryonic stem cell types. Depending on the nature of the injury or disease and method of delivery, these cells may produce factors that protect tissue or modulate the body's response to injury and provide significant therapeutic benefit, or differentiate in vivo into a variety of cells to help augment functional improvement and recovery. Other non-embryonic stem or progenitor cells appear to have more limited plasticity.
Second, unlike most other cell types, MultiStem cells can be produced in significant quantities, thereby enabling scaled and reliable production. This enables Athersys and its collaborators to produce a standardized, well characterized therapeutic product in a reliable and cost effective manner. Athersys has established cultures and carried cells through sufficient passages to represent potentially hundreds of thousands of potential doses from an individual donor. In March 2007, we and our manufacturing partner, Lonza, announced the successful establishment of a Master Cell Bank produced under GMP and the production of clinical grade material for our initial clinical trials. Cells are harvested from a pre-qualified donor and then expanded to form a Master Cell Bank. At each step of the MultiStem production process, cells are analyzed and qualified according to pre-established criteria to ensure that a consistent, well characterized product candidate is produced. In contrast, other adult stem and progenitor cells exhibit much more limited doubling potential, which limits the number of potential doses obtained from a single production run and/or results in significant loss of potency.
Third, MultiStem cells have a demonstrated record of safety and efficacy in a range of pre-clinical studies and validated disease models. Unlike embryonic stem cells (ESC), MultiStem cells are not derived from or harvested from developing embryos, and do not appear to lead to the formation of tumor like growths (teratomas) or inappropriately placed tissue (also referred to as “ectopic” tissue) when administered to animals in a variety of disease models. Multiple in vivo experiments, in which MultiStem cells have been administered to animals, demonstrate the cells have engrafted and differentiated into functional cells in a variety of tissue and organ systems without forming teratomas.
Finally, MultiStem cells display important immunological characteristics which may make them useful as an “allogeneic” or universal donor type product. Specifically, MultiStem cells appear to be immune privileged / immune system advantaged. For instance, in vitro experiments demonstrate these cells can suppress an undesired T-cell response. Furthermore, in allogeneic animal models of disease MultiStem cells have demonstrated significant therapeutic benefit. In contrast, with conventional bone marrow or organ transplantation, the donor and the recipient typically have to be very carefully matched to reduce the odds of tissue rejection. This severely limits the number of transplants that can take place, and frequently requires that the organ transplant recipient must remain on chronic immunosuppressive therapy – which can have significant risks and side effects, including an increased incidence of cancer.
If MultiStem cells display similar results in humans (i.e. allogeneic therapeutic benefit without the need for extensive genetic matching or chronic immunosuppressive therapy), then the MultiStem platform would provide both large scale production capability and true "off-the-shelf" utility ... making it unique among cell therapeutics, and representing a potential breakthrough in the field of regenerative medicine.
MultiStem allows us to pursue multiple high value commercial opportunities from a single product platform, since we believe it has potential application in a range of disease states and therapeutic areas. For example, based on numerous preclinical discussions with the FDA, we believe that we will be able to use data and information from preclinical safety studies for the development of MultiStem for treating multiple distinct diseases in parallel. This will be achieved by establishing a central file with the FDA, also known as a Master File, that contains data from multiple safety studies as well as information related to product manufacturing and characterization. As a result, we expect to be able to efficiently add additional clinical indications as we further expand the scope of potential applications for MultiStem, enabling us to reduce costs and shorten development timelines in comparison to traditional single-use drug development programs.
In addition to the direct therapeutic application of unmodified MultiStem cells, more specialized therapies may be developed. For example, undifferentiated cells may be used to produce cells that are targeted or primed to engraft or develop into various specific cell types, such as heart muscle cells, β-islet cells, blood or immune cells, bone, cartilage or other cell types. This process of specialized cellular development is also referred to as “differentiation”. As an alternative or complementary approach to the use of MultiStem cells, modified, primed, or differentiated cell populations may be optimized for certain clinical indications.