OssioStem-matched multipotent MSC (M3): banked, low passage bone marrow MSC for treatment of hematopoietic acute radiation syndrome.

OssioStem 匹配的多能 MSC (M3)：库存的低通道骨髓 MSC，用于治疗造血急性放射综合征。

• 批准号: 9913377
• 负责人: ERIK J. WOODS
• 金额: $ 49.5万
• 依托单位: OSSIUM HEALTH, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-19 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9913377
• 关键词: Acute Graft Versus Host Disease; Address; Affect; Allogenic; Aplastic Anemia; Aspirate substance; Autologous; Biological Process; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Marrow Transplantation; Cadaver; Cell Count; Cell Therapy; Cells; Characteristics; Clinical Data; Clinical Research; Clinical Trials; Colony-Forming Units Assay; Complication; Cryopreservation; Data; Devices; Digestion; Dose; Engraftment; Exposure to; Failure; Family suidae; Goals; Harvest; Head; Health; Hematopoietic; Hematopoietic Cell Production; Hematopoietic Neoplasms; Hematopoietic Stem Cell Transplantation; Hematopoietic System; Hematopoietic stem cells; Immune Cell Suppression; Immune response; Immune system; Incidence; Industrial Accidents; Infusion procedures; Ionizing radiation; Licensure; Life; Liver; Living Donors; Medical; Medicine; Mesenchymal; Methods; Miniature Swine; Modeling; Mus; Nuclear; Nuclear Warfare; Occupational Accidents; Organ; Organ Donor; Pathology; Patients; Peptide Hydrolases; Phenotype; Procedures; Process; Production; Property; Protocols documentation; Radiation; Radiation Toxicity; Radiation exposure; Recovery; Research; Risk; Safety; Savings; Severities; Skin; Source; Spinal; Sternum; Stream; Stromal Cells; Supporting Cell; Syndrome; System; Terrorism; Testing; Therapeutic; Time; Tissue Donors; Tissues; Transplant Recipients; Transplantation; Validation; analog; animal rule; bone; cell injury; cell regeneration; cost effective; disorder prevention; effectiveness validation; efficacy study; gastrointestinal; gastrointestinal system; graft failure; graft vs host disease; immunoregulation; innovation; irradiation; long bone; mouse model; next generation; novel; peripheral blood; pre-clinical; prevent; product development; programs; reconstitution; rib bone structure; soft tissue; stem; stem cell therapy; stem cells; success; tissue regeneration; vertebra body

ABSTRACT The hematopoietic subsyndrome of acute radiation syndrome (H-ARS) is induced with even moderate exposure to ionizing radiation, which is lethal to hematopoietic stem cells (HSC) in the bone marrow (BM). Hematopoietic stem cell transplant (HSCT) is a potential life-saving treatment for H-ARS victims; however, it is not generally recommended due to commonly associated complication of graft-versus-host disease. Recent clinical trials, including that of our collaborator, have demonstrated that mesenchymal stromal/stem cell (MSC) infusions prevent/treat graft-versus-host-disease (GVHD) and reduce graft failure following HSCT. These salutary effects of MSC are due to potent immunomodulatory properties of the cells. Furthermore, MSC possess many other therapeutic properties shown to ameliorate pathologies associated with other ARS syndromes effecting the gastrointestinal system, skin and liver. Thus, MSC have the potential to treat the full spectrum of pathologies associated with ionizing radiation exposure. Ossium Health is developing a unique source of BM-derived multipotent MSC obtained from deceased organ donors. This cellular therapy, termed OssioStem-M3 (matched multipotent MSC) has a distinct advantage over other MSC sources in that it is donor-matched to a source for HSCT grafts (OssioStem-HSC) obtained from the same donors. Additionally, the large volumes of BM that can be obtained from a deceased donor yield exceptionally high numbers of MSC. This is important given that efficacy of MSC for supporting HSCT is negatively related to passage number; thus, low passage OssioStem-M3 is superior to “third party” MSC obtained from living donors which must be amplified through many passages. We propose here to optimize methods for isolation of OssioStem-M3 and thoroughly characterize their physical characteristics and biological function. We also propose to demonstrate efficacy in large (porcine) and small (mouse) models of H-ARS. Finally, we will build and test next generation devices for increasing the consistency and throughput of OssioStem-HSC production. The overall product of this research program will be a robust production process and a compelling preclinical package to justify definitive studies to support FDA approval for H-ARS under the Animal Rule.

摘要