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: 10271661
• 负责人: ERIK J. WOODS
• 金额: $ 6.85万
• 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/10271661
• 关键词: Award; Biological Process; Bone Marrow; Budgets; Cell Therapy; Cells; Characteristics; Clinical Trials; Complication; Devices; Direct Costs; Exposure to; Family suidae; Funding; Grant; Health; Hematopoietic; Hematopoietic Cell Production; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Histopathology; Infusion procedures; Ionizing radiation; Life; Liver; Living Donors; Mesenchymal; Methods; Organ Donor; Parents; Pathology; Process; Production; Property; Radiation Toxicity; Radiation exposure; Research; Savings; Site; Skin; Source; Sum; Supporting Cell; Syndrome; Testing; Therapeutic; animal rule; arm; base; cost; gastrointestinal system; graft failure; graft vs host disease; immunoregulation; meetings; mouse model; next generation; pre-clinical; prevent; programs; stem cell therapy; stem cells

Abstract of funded parent award 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. Abstract for supplement Supplemental funds are requested to cover a budget deficit caused by having to place the porcine H-ARS study at a new study site after the original site (Altasciences) discontinued their program. These funds will be used to cover the porcine H-ARS study budgetary shortfall and add a control arm. The supplemental amount requested is based on a quote provided by CRL on September 11, 2020 (quote number CRL272922). The amount quoted for 4 study groups was $389,580. With the inclusion of the additional of optional histopathology costs ($39,800), the total cost for the study was brought to $429,380 (ie., the sum of $389,580 + $39,800). Note that the histopathology costs were part of the original quote but were removed in consideration of meeting the originally budgeted amount for the study. Thus, the request for supplementing the CRL study is $115,380 which is the difference between $429,380 and $324,000.

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