Stroke is the leading cause of long term disability with majority of strokes occuring in the aged. There is a great need for therapies that can reduce neurological deficits from stroke and extend the healthy, active years of life of the affected patients. Thus the long term objective of this proposal is to develop a cellular therapeutic product that can be administered beyond the acute period after stroke for the purpose of restoring neurological function. Adult Bone Marrow derived Stromal/Stem Cells (BMSCs) have been shown to improve neurological function in animal models of stroke and a recent small clinical trial, even when the cells were administered well beyond the 3 hour window mandated for currently approved treatments of stroke patients. Adipose derived Stromal/Stem cells (ASCs) are similar to BMSCs in some ways but unique in other ways, and can be easily isolated in large quantities from lipoaspirates obtained during elective liposuction procedures. Theradigm has gained both the knowledge and intellectual property to produce and use both BMSCs and ASCs for the treatment of neurological diseases. We hypothesize that ASCs will display greater efficacy relative to BMSCs for treatment of stroke. In this Phase-1 proposal ASCs and BMSCs will be isolated from transgenic rats expressing a human alkaline phosphatase (AP) marker. The cells will be delivered intravenously to aged rats subjected to stroke to determine which cell type is more efficacious in improving neurological function after stroke. The distribution of the transplanted cells in the brain will be assessed histologically using the AP marker. Additionally, migration of ASCs or BMSCs towards components of ischemic brain tissue obtained from rats at various time points after stroke will be measured in vitro to determine the optimal therapeutic window for delivering the cells, which can be subsequently confirmed in the rat stroke model with the chosen cell type. Results from this Phase-1 study will be used in Phase-2 to further investigate either human ASCs or human BMSCs in suitable animal models in terms of both efficacy and safety, along with process development for manufacture of large scale clinical grade human cells. Adult derived cells such as ASCs and BMSCs that are immunologically inert could potentially be developed into an "off the shelf product that can improve the quality of life of millions of stroke survivors living with a wide range of neurological deficits.
Thesaurus Terms: adipose tissue, cell population study, hematopoietic stem cell, human therapy evaluation, neuroprotectant, nonhuman therapy evaluation, stem cell transplantation, stroke therapy, stromal cell, therapy design /development alkaline phosphatase, animal old age, biomarker, brain, chemotaxis, disease /disorder model, phenotype genetically modified animal, histology, immunocytochemistry, laboratory rat, tissue /cell culture
