Molecular Repair of Diabetic Mesenchymal Stem Cells (dMSC) for Peripheral Arterial Disease

糖尿病间充质干细胞 (dMSC) 治疗外周动脉疾病的分子修复

• 批准号: 10045514
• 负责人: LUKE Packard BREWSTER
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10045514
• 关键词: Acute; Affect; Amputation; Arteries; Blood Platelets; Blood Vessels; CCL2 gene; Cell Culture Techniques; Cell Therapy; Cell Transplantation; Cells; Clinical; Data; Defect; Diabetes Mellitus; Endothelial Cells; Gel; Glucose; Goals; Health; Hindlimb; Human; Hydrogels; Impairment; In Vitro; Incidence; Interdisciplinary Study; Ischemia; Leg; Limb Salvage; Mesenchymal Stem Cells; Methods; Molecular; Natural regeneration; Nude Mice; Operative Surgical Procedures; Pathway interactions; Patients; Perfusion; Peripheral Blood Stem Cell; Peripheral arterial disease; Phenotype; Regenerative Medicine; Regenerative capacity; Research; Risk; Signal Transduction; Testing; Therapeutic; Therapy trial; Tissue Transplantation; Tissues; Translating; Vascular blood supply; Veterans; Work; diabetic; diabetic patient; diabetic ulcer; effectiveness testing; experience; fetal bovine serum; immunoregulation; improved; in vitro testing; in vivo; in vivo Model; in vivo evaluation; in vivo regeneration; macrophage; military veteran; mouse model; optimism; paracrine; premature; prevent; recruit; regeneration function; regenerative; regenerative approach; regenerative cell; repaired; senescence; stem cell biology; stem cell survival

Diabetes and peripheral arterial disease (PAD) disproportionately affect our nation's Veterans. Diabetic patients have limited collateralization and regenerative capacity in their tissues. Diabetic patients with peripheral arterial disease have severe ischemic complications and are at grave risk of major amputation. Reversing tissue ischemia by surgical revascularization prevents amputations, but many patients with diabetes and peripheral arterial disease are not fully treatable by surgical revascularization. Regenerative cell-based therapies may enable a full step forward in re-establishing or regenerating the vascular supply of the leg to prevent amputations. We have identified a unique intracellular signaling defect in diabetic mesenchymal stem cells that can be favorably modified to improve these cells. This proposal will test the effectiveness, durability and then mechanism by which this approach works under diabetic conditions using relevant in vitro and in vivo models. Positive results will be used to translate these methods to Veterans with diabetes and PAD.

糖尿病和外周动脉疾病（PAD）对我们国家的退伍军人影响尤为严重。糖尿病 患者在其组织中具有有限的抵押和再生能力。糖尿病患者 外周动脉疾病具有严重的缺血性并发症，并有严重的截肢风险。 通过外科血管重建逆转组织缺血可以防止截肢，但许多糖尿病患者 和外周动脉疾病不能完全通过外科血管重建治疗。基于再生细胞的 治疗可以在重建或再生腿部的血管供应方面向前迈出一大步 防止截肢。我们已经确定了糖尿病间充质干细胞中独特的细胞内信号传导缺陷 可以有利地修饰以改善这些细胞的细胞。这项建议将测试的有效性，耐用性 然后使用相关的体外和体内研究， 模型积极的结果将用于将这些方法转化为糖尿病和PAD退伍军人。