Stem Cell-based therapy for Lymphedema

淋巴水肿的干细胞疗法

基本信息

批准号：
9102215
负责人：
Young-Sup Yoon
金额：
$ 40.11万
依托单位：
EMORY UNIVERSITY
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：
2015-07-01 至 2019-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9102215
关键词：
Accounting Address Alabama Animal Model Biocompatible Materials Biomedical Engineering Blood Vessels Cardiovascular Diseases Cardiovascular system Cell Lineage Cell Survival Cell Therapy Cell Transplantation Cell Transplants Cell physiology Cells Chronic Clinical Communicable Diseases Defect Developed Countries Development Disease Edema Embryo Engineering Ethics Extracellular Matrix Face Failure Fibrosis Gel Generations Goals Growth Human Human Engineering Image Immunologics Incidence Infection Inflammation Inherited Injectable Innovative Therapy Lead Light Liquid substance Lymph Lymphatic Lymphatic Endothelial Cells Lymphatic vessel Lymphedema Magnetic Resonance Imaging Measurement Methods Molecular Morbidity - disease rate Operative Surgical Procedures Pain Peptides Play Pluripotent Stem Cells Proteins Protocols documentation Reporting Research Personnel Role Series Serum Somatic Cell Staging Stem cells System Techniques Testing Therapeutic Therapeutic Effect Therapeutic Intervention Therapeutic Uses Universities Vascular System Venous Work adult stem cell base bioluminescence imaging cancer radiation therapy design embryonic stem cell human embryonic stem cell in vivo induced pluripotent stem cell innovation insight interstitial nanostructured neovascularization non-genetic novel novel therapeutics palliative paracrine pluripotency primary lymphedema public health relevance regenerative research study restoration stem transcription factor two-dimensional

项目摘要

DESCRIPTION (provided by applicant): Lymphedema is the accumulation of lymphatic fluid in the interstitial spaces caused by a defect in the lymphatic vascular system. It is marked by edema, chronic inflammation, and fibrosis, which can lead to painful, disfiguring abnormalities and serious infection. While primary lymphedema occurs infrequently on a hereditary or idiopathic basis, secondary lymphedema is common worldwide, primarily due to infectious disease or radical surgery and radiotherapy for cancer. Despite a continuous increase in the incidence of lymphedema, current therapeutic options are limited to palliative surgical and conservative techniques. Recent progress toward understanding the molecular mechanisms of new lymphatic vessel growth has shed new light on the treatment of lymphedema. Growth factor therapy has yet to show clear clinical benefits in treatment of diseases characterized by deficient arterial or venous vasculature; using a similar strategy to approach lymphedema may face similar hurdles. Recent groundbreaking studies have demonstrated that introduction of pluripotency-associated transcription factors can reprogram somatic cells into embryonic stem (ES)-like cells, referred to as induced pluripotent stem cells (iPSCs). The discovery of iPSCs has presented the opportunity for ES cell-equivalent stem cells to be used therapeutically without concerns about immunologic incompatibility and ethical controversy. Recently, we have developed protocols to efficiently differentiate human iPSCs and ESCs into lymphatic endothelial cell (LEC) lineages. We therefore propose to study the therapeutic effects of hPSC-derived LECs, and their bioengineered derivatives with extracellular matrix-mimicking nanomatrix, on experimental lymphedema. In aim 1, we will develop a novel clinically compatible method to differentiate hPSCs into the lymphatic endothelial lineage and isolate pure hPSC-LECs. In aim 2, we will engineer hPSC-derived LECs with peptide amphiphile-based nanomatrix gel for enhancing cell survival and function. In aim 3, we will determine the effects of hPSC-derived LECs and their bioengineered constructs on experimental lymphedema. We anticipate that the results of the proposed experiments will yield new insight into the role of novel stem cell-based therapy for treating lymphedema.

描述（由申请人提供）：淋巴水肿是由于淋巴血管系统缺陷引起的淋巴液在组织间隙中积聚，其特点是水肿、慢性炎症和纤维化，可导致疼痛、毁容异常和严重的症状。虽然原发性淋巴水肿很少因遗传或特发性而发生，但继发性淋巴水肿在世界范围内很常见，主要是由于感染性疾病或癌症的根治性手术和放射治疗。尽管淋巴水肿的发病率持续增加，但目前的治疗选择仅限于姑息性手术和保守技术。最近在了解新淋巴管生长的分子机制方面取得的进展尚未为淋巴水肿的治疗带来新的曙光。在治疗以动脉或静脉血管系统缺陷为特征的疾病方面显示出明显的临床益处；使用类似的策略来治疗淋巴水肿可能会面临类似的障碍。最近的突破性研究表明，引入多能性相关转录因子可以重新编程。体细胞转化为胚胎干细胞 (ES) 样细胞，称为诱导多能干细胞 (iPSC) iPSC 的发现为 ES 细胞等效干细胞的治疗应用提供了机会，而无需担心免疫不相容性和争议。，我们开发了有效地将人类 iPSC 和 ESC 分化为淋巴内皮细胞 (LEC) 谱系的方案，因此我们建议研究 hPSC 衍生的 LEC 及其治疗效果。具有细胞外基质模拟纳米基质的生物工程衍生物，针对实验性淋巴水肿。在目标 1 中，我们将开发一种临床新颖的兼容方法，将 hPSC 分化为淋巴管内皮谱系并分离纯 hPSC-LEC。在目标 2 中，我们将设计 hPSC 衍生的细胞。 LEC 与基于肽双亲物的纳米基质凝胶可增强细胞存活和功能在目标 3 中，我们将确定以下效果： hPSC 衍生的 LEC 及其生物工程构建物对实验性淋巴水肿的作用我们预计所提出的实验结果将为新型干细胞疗法治疗淋巴水肿的作用提供新的见解。