Therapeutic Angiogenesis by Universal Donor Endometrial Regenerative Cells (ERC) Abstract The proposed study seeks to develop a practical, off the shelf, universal donor, cell therapy for an advanced form of peripheral artery disease termed "critical limb ischemia" (CLI). The major problem facing CLI patients is lack of proper circulation to the extremities. Although a basal level of collateral vessel formation has been documented in these patients, in many cases it is insufficient to prevent amputation. Methods of augmenting the process of collateral vessel formation through administration of angiogenic cytokines have largely failed clinically [1-3]. One explanation for this has been that cytokine administration was performed under conditions that were not physiological, both in terms of sequence and combinations. A more therapeutically promising method has been administration of autologous stem cells which secrete angiogenic cytokines under what appears to be more physiological conditions. Numerous clinical trials have demonstrated benefit using bone marrow and mobilized peripheral blood stem cell populations, which are reviewed in the following reference [4]. Unfortunately, adult autologous cells display reduced angiogenic capacity, especially in CLI patients [5, 6]. Additionally, the procedures for harvesting stem cells from the bone marrow or peripheral blood are considered to be dangerous in patients with CLI due to existing comorbidities [7, 8]. From a practical perspective autologous therapy can only be performed at specialized centers which have certified clean rooms and experience with cell processing. A novel stem cell population termed "endometrial regenerative cells" (ERC) has been identified by Medistem, Inc., that the company is developing with General BioTechnology, LLC as a "universal donor" population. To date this collaboration has resulted in a cell population that inhibits inflammatory responses, do not elicit T cell reactivity, and can survive in allogeneic and xenogeneic hosts in absence of immune suppression both in vitro and in vivo. Given the large amount of angiogenic growth factor secretion and ability to stimulate angiogenesis, the ERC may be a commercially viable substitute for autologous stem cell implantation that circumvents the problems of: extraction, age and disease associated stem cell dysfunction, and requirement for clean room facilities at the point of care. The current proposal seeks support to expand on existing efficacy evaluation so as to permit entry into Phase Ib/II clinical trials.
Public Health Relevance: The project aims to augment existing safety and manufacturing data to submit a Phase Ib/II IND for treatment of critical limb ischemia using a novel adult stem cell population developed by Medistem termed Endometrial Regenerative Cells (ERC). Existing data demonstrates ERC are potently angiogenic, anti-inflammatory, and can be used in a "universal donor" manner, thus providing an easy to use, off the shelf cellular therapy for a condition that lacks therapeutic options besides amputation.
Thesaurus Terms: 21+ Years Old; Adult; Age; Agreement; Allogenic; Amputation; Animals; Anti-Inflammatories; Anti-Inflammatory Agents; Anti-Inflammatory; Antiinflammatories; Antiinflammatory Agents; Autologous; Balb/C; Biological Models; Biotechnology; Blood Circulation; Bloodstream; Bone Marrow; Bone Marrow Blood-Deriving Cell; Bone Marrow Blood-Forming Cell; Bone Marrow Cells; Bone Marrow Stem Cell; Cell Count; Cell Function; Cell Number; Cell Process; Cell Therapy; Cell Physiology; Cells; Cellular Function; Cellular Physiology; Cellular Process; Circulation; Clinical; Clinical Trials; Clinical Trials, Unspecified; Closure By Ligation; Collaborations; Comorbidity; Data; Disease; Disorder; Dose; Dysfunction; Effectiveness; Electromagnetic, Laser; Endometrial; Evaluation; Extremities; Femoral Artery; Functional Disorder; Gfac; Growth Agents; Growth Factor; Growth Factors, Proteins; Growth Substances; Harvest; Human; Human, Adult; Human, General; Inflm; Image; Immune; Immunology; Immunology (Including Brmp); Immunology (Nci Program); Immunosuppression Effect; Immunosuppressions (Physiology); Immunosuppressive Effect; In Vitro; Inbred Balb C Mice; Inflammation; Inflammatory Response; Injection Of Therapeutic Agent; Injections; Ischemia; Laboratories; Lasers; Ligation; Limb Structure; Limbs; Mammals, Mice; Man (Taxonomy); Man, Modern; Measures; Methods; Mice; Mice, Inbred Balb C; Model System; Modeling; Models, Biologic; Mother Cells; Mouse, Balb C; Murine; Mus; Muscle Cells; Muscle Cells, Mature; Myocytes; Nod/Scid Mouse; Natural Immunosuppression; Non-Trunk; P50 Mechanism; P50 Program; Pbmc; Pbsc; Patients; Peripheral Blood Mononuclear Cell; Peripheral Blood Stem Cell; Peripheral Stem Cells; Peripheral Arterial Disease; Phase; Physiologic; Physiological; Physiopathology; Population; Procedures; Process; Progenitor Cells; Protocol; Protocols Documentation; Publishing; Radiation, Laser; Reticuloendothelial System, Bone Marrow; Route; Safety; Series; Side; Specialized Center; Stem Cells; Structure Of Femoral Artery; Subcellular Process; Symptoms; T-Cells; T-Lymphocyte; Therapeutic; Therapy, Cell; Thymus-Dependent Lymphocytes; Time; Work; Abstracting; Adult Human (21+); Adult Stem Cell; Angiogenesis; Angiogenesis Therapy; Cell-Based Therapy; Clinical Investigation; Cytokine; Disease/Disorder; Efficacy Evaluation; Experience; Experiment; Experimental Research; Experimental Study; Femoral Artery; Imaging; Immunosuppression; Implantation; In Vivo; Intraperitoneal; Meetings; Mouse Model; Novel; Pathophysiology; Peripheral Blood; Point Of Care; Prevent; Preventing; Public Health Relevance; Regenerative; Research Study; Response; Stem Cell Population; Therapeutic Angiogenesis; Thymus Derived Lymphocyte
