Allogeneic Mesechymal Stem Cells

Angeles Health only uses Adult, Allogeneic Mesechymal Stem Cells to treat Stroke patients.

Allogeneic stem cells are blood-forming stem cells (cells from which all blood cells develop) from a genetically similar, but not identical, donor. Research efforts in the field of stem cell biology have accelerated and intensified during the last few decades and have provided important information on the developmental roles and pathophysiologic responses of stem cells. Stem cells can be found in many tissues (e.g., bone marrow, brain, adipose tissue, muscle, and eye) and can be isolated from many different tissue sources. The advances in our understanding of stem cell biology and the multiple sources of stem cells have generated significant interest in the therapeutic potential of endogenous stem cell mobilization and exogenous stem cell administration.

Mesenchymal stem cells, or MSCs, are multi-potent stem cells that can differentiate into a variety of cell types. MSCs have been isolated from a number of sources, including bone marrow, adipose tissue, peripheral blood, amniotic fluid and umbilical cord blood. The MSCs manufactured for this study are a subset of non-hematopoietic stem cells derived from the bone marrow of healthy, adult donors, and have the ability to migrate and differentiate into multiple cell types depending on the local environment and extracellular matrix, and include cartilage, bone, adipose tissue, vasculature and neurons. Several recent reports demonstrates that human MSCs derived from adult human bone marrow can differentiate in culture to neuronal stem cells that have all the neuroectodermal markers appropriate for this lineage, including nestin and otx1.

In addition to their ability to differentiate into multiple different cell types that would be contributory to the recovery and repair of the brain by replacing destroyed cells, mesenchymal stem cells also secrete angiogenins, cytokines and trophic factors that can support and stimulate multiple other cell types. The cascade of cellular events following the release of these cytokines and trophic factors would also potentially lead to beneficial effects by restoring blood supply, by rescuing cells at risk, and by stimulating the remaining cell populations to repair and propagate new cells and synaptic connections. A recent study in a rodent stroke model demonstrated an increase in hMSC-enhanced angiogenesis in the ischemic brain region that was thought to be due to the proliferation and migration of endothelial cells from adjacent tissue and from circulating endothelial precursors that was preceded by an increase in endogenous VEGF and VEGF receptor 2. MSCs are also anti-inflammatory, immunomodulatory (i.e., down regulate the T cell immune system), and immune-privileged, allowing them to be used in allogeneic transplantation without the concomitant use of immunosuppressive medications.

Another important characteristic of MSCs is their apparent ability to survive in an ischemic environment, which may make them particularly useful in the setting of ischemic brain disease. In addition, this characteristic may also be beneficial in age-related neurodegenerative diseases that are often accompanied by a loss or reduction of cerebrovascular perfusion related to neurodegeneration and/or atherosclerosis.

Interestingly, in preclinical and clinical study reports there is typically a rapid effect that is observed during the first few days post-transplant that occurs too quickly to be due to a neuronal effect. This is likely due to a chaperone effect that relies on the production and release of cytokines and neurotrophic factors that can rescue damaged cells, promote the activity and migration of endogenous neural stem cells, and induce synaptogenesis.

In summary, MSCs can be differentiated into multiple cell types, are relatively easy to expand, and have favorable immunologic characteristics that make MSCs promising therapeutics for the treatment of neurodegenerative conditions.