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: 10553638
• 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 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10553638
• 关键词: Acute; Affect; Amputation; Arteries; Biology; Blood Platelets; Blood Vessels; CCL2 gene; Cell Therapy; Cell Transplantation; Cell secretion; Cells; Clinical; Data; Defect; Diabetes Mellitus; Endothelial Cells; Fibrin; Gel; Glucose; Goals; Health; Hindlimb; Human; Hydrogels; Impairment; In Vitro; Incidence; Inflammation; Interdisciplinary Study; Ischemia; Leg; Limb Salvage; Macrophage; Mesenchymal Stem Cells; Methods; Molecular; Natural regeneration; Nude Mice; PIK3CG gene; Pathway interactions; Patient Recruitments; 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; Vascular regeneration; Veterans; Work; comparison control; delivery vehicle; diabetic; diabetic patient; diabetic ulcer; effectiveness testing; experience; fetal bovine serum; immunoregulation; improved; in vivo; in vivo Model; in vivo evaluation; in vivo regeneration; military veteran; mouse model; optimism; paracrine; patient retention; premature; prevent; recruit; regeneration function; regenerative; regenerative approach; regenerative cell; repaired; revascularization surgery; senescence; stem cell therapy

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）对我国退伍军人的影响尤为严重。糖尿病患者 患者组织的抵押和再生能力有限。糖尿病患者 外周动脉疾病会导致严重的缺血性并发症，并面临严重截肢的风险。 通过手术血运重建逆转组织缺血可以防止截肢，但许多糖尿病患者 外周动脉疾病不能通过血运重建术完全治疗。基于再生细胞 治疗可能会在重建或再生腿部血管供应方面迈出一大步 防止截肢。我们在糖尿病间充质干细胞中发现了独特的细胞内信号传导缺陷 可以对细胞进行有利的修饰以改善这些细胞。该提案将测试有效性、持久性 然后使用相关的体外和体内该方法在糖尿病条件下发挥作用的机制 模型。积极的结果将用于将这些方法应用到患有糖尿病和外周动脉疾病的退伍军人身上。

项目成果

Evaluation of Lower Extremity Calcium Score as a Measure of Peripheral Arterial Disease Burden and Amputation Risk.

评估下肢钙评分作为外周动脉疾病负担和截肢风险的衡量标准。

• DOI: 10.1016/j.avsg.2023.02.009
• 发表时间: 2023
• 期刊: Annals of vascular surgery
• 影响因子: 1.5
• 作者: Lee,Sujin;Kalra,Kanika;Kashikar,Aditi;Redpath,Benjamin;Bernheim,Adam;Brewster,Luke;Shaw,Leslee;Arya,Shipra
• 通讯作者: Arya,Shipra