Evaluating Revascularization with Encapsulated MSCs Overexpressing Hemeoxygenase-1

使用过表达 Hemeoxygenase-1 的封装 MSC 评估血运重建

基本信息

  • 批准号:
    8983643
  • 负责人:
  • 金额:
    $ 5.56万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-08-01 至 2016-06-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Peripheral vascular disease (PVD) affects up to 20% of the general population. The resulting morbidity in the form of leg pain, immobility and amputation can be devastating. One year mortality in patients with critical limb ischemia is 25% with approximately 30% of patients requiring amputation. Patients with diabetes are approximately three times as likely to have PVD. While there is no definitive treatment for PVD, the only therapies available are surgical, such as endovascular interventions with stents or vascular bypass grafts. Despite these interventions, up to 34% of patients experience limb loss by 12 months. Clinical trials involving gene and cell based therapies have demonstrated safety but have not proven to be beneficial in preventing amputation. Studies from our laboratory and others suggest that paracrine factors secreted by implanted stem cells facilitate blood vessel formation in vivo through secretion of angiogenic factors. Hemoxygenase-1 (Ho-1) is a multifunctional protein that improves cell survival and induces secretion of pro-angiogenic factors such as Vascular Endothelial Growth Factor (VEGF) and Stromal cell Derived Factor-1 (SDF-1). In Aim 1, we plan on using alginate-encapsulated stem cells that overexpress Ho-1 to determine if we can further enhance blood vessel formation, increase blood flow, and preserve tissue function. In Aim 2, we propose to investigate contributing factors involved in improving revascularization including improved homing of endothelial progenitor cells. In Aim 3, we will evaluate the benefit of these Ho-1 overexpressing stem cells in mice with diabetes, where blood vessel formation is greatly impaired. Given that stem cell therapies are gaining momentum in various fields, our combined gene and cell therapy approach delivers a logical next step in providing sustained pro-angiogenic stimuli for local therapy while segregating genetic material from the recipient. Furthermore, if proven to be beneficial in diabetic patients, this approach could be applied in regenerative medicine to a wide range of cardiovascular diseases including heart attack and stroke.
 描述(由申请人提供):外周血管疾病(PVD)影响高达20%的普通人群。由此造成的腿部疼痛、行动不便和截肢等形式的发病率可能是毁灭性的。严重肢体缺血患者的一年死亡率为25%,约30%的患者需要截肢。糖尿病患者患PVD的可能性约为正常人的三倍。虽然PVD没有明确的治疗方法,但唯一可用的治疗方法是外科手术,例如使用支架或血管旁路移植物的血管内介入。尽管有这些干预措施,高达34%的患者在12个月内经历肢体丧失。涉及基因和细胞疗法的临床试验已经证明了安全性,但尚未证明在预防截肢方面有益。我们实验室和其他实验室的研究表明,植入干细胞分泌的旁分泌因子通过分泌血管生成因子促进体内血管形成。血红素加氧酶-1(Ho-1)是一种多功能蛋白,可提高细胞存活率并诱导促血管生成因子(如血管内皮生长因子(VEGF)和基质细胞衍生因子-1(SDF-1))的分泌。在目标1中,我们计划使用过表达Ho-1的藻酸盐包封的干细胞来确定我们是否可以进一步增强血管形成,增加血流量和保护组织功能。在目标2中,我们建议研究参与改善血管重建的因素,包括改善内皮祖细胞的归巢。在目标3中,我们将评估这些Ho-1过表达干细胞在糖尿病小鼠中的益处,其中血管形成严重受损。鉴于干细胞疗法在各个领域的发展势头越来越好,我们的基因和细胞联合治疗方法提供了一个合乎逻辑的下一步,即为局部治疗提供持续的促血管生成刺激,同时将遗传物质与受体分离。此外,如果证明这种方法对糖尿病患者有益,那么这种方法可以应用于再生医学,以治疗各种心血管疾病,包括心脏病发作和中风。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Reply to the Letter to the Editor: "GDF-15 - A matter of the heart or the kidney?".
回复给编辑的信:“GDF-15 - 心脏还是肾脏的问题?”。
Assessing Pregnancy, Gestational Complications, and Co-morbidities in Women With Congenital Heart Defects (Data from ICD-9-CM Codes in 3 US Surveillance Sites).
评估先天性心脏缺陷女性的妊娠、妊娠并发症和合并症(数据来自美国 3 个监测站点的 ICD-9-CM 代码)。
  • DOI:
    10.1016/j.amjcard.2019.12.001
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Raskind-Hood,Cheryl;Saraf,Anita;Riehle-Colarusso,Tiffany;Glidewell,Jill;Gurvitz,Michelle;Dunn,JulieE;Lui,GeorgeK;VanZutphen,Alissa;McGarry,Claire;Hogue,CarolJ;Hoffman,Trenton;RodriguezIii,FredH;Book,WendyM
  • 通讯作者:
    Book,WendyM
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Anita Saraf其他文献

Anita Saraf的其他文献

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{{ truncateString('Anita Saraf', 18)}}的其他基金

Molecular and Functional Evaluation of NOTCH1 Deficient iPSC Derived Cardiomyocytes in Hypoplastic Left Heart Syndrome
NOTCH1 缺陷 iPSC 来源的心肌细胞在左心发育不全综合征中的分子和功能评估
  • 批准号:
    10350802
  • 财政年份:
    2022
  • 资助金额:
    $ 5.56万
  • 项目类别:
Molecular and Functional Evaluation of NOTCH1 Deficient iPSC Derived Cardiomyocytes in Hypoplastic Left Heart Syndrome
NOTCH1 缺陷 iPSC 来源的心肌细胞在左心发育不全综合征中的分子和功能评估
  • 批准号:
    10590735
  • 财政年份:
    2022
  • 资助金额:
    $ 5.56万
  • 项目类别:

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