Interfacial Adapters for Improved Cell Delivery to Tissues

用于改善细胞向组织输送的界面适配器

• 批准号: 7325627
• 负责人: PAUL T HAMILTON
• 金额: $ 24.99万
• 依托单位: AFFINERGY ,INC
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-20 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7325627
• 关键词: Adhesions; Affinity; Animal Disease Models; Basement membrane; Binding; Biocompatible Materials; Biopolymers; Blood Vessels; Cell Therapy; Cells; Chemistry; Clinical Treatment; Clinical Trials; Collagen; Collagen Type I; Communication; Compatible; Complex; Diabetes Mellitus; Disease; Drainage procedure; Engraftment; Extracellular Matrix; Face; Fluorescence-Activated Cell Sorting; Goals; Growth; Heart Diseases; Human; Incubated; Inflammation; Injection of therapeutic agent; Laminin; Lead; Libraries; Lymphatic; Malignant Neoplasms; Mediating; Modeling; Muscle; Myoblasts; Myocardium; Names; Pan Genus; Parkinson Disease; Peptides; Phage Display; Phase; Process; Proteins; Range; Rattus; Regenerative Medicine; Research Institute; Saints; Serum Proteins; Signal Transduction; Site; Skeletal Muscle; Skeletal Myoblasts; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Specific qualifier value; Specificity; Surface; Technology; Testing; Therapeutic; Tissue Survival; Tissues; To specify; Wound Healing; base; cell type; cellular engineering; design; human disease; improved; in vivo; interfacial; migration; new technology; peptide chemical synthesis; pre-clinical; prevent; programs; tissue regeneration

DESCRIPTION (provided by applicant): Many human diseases can theoretically be treated by injection of healthy or engineered cells into damaged tissue, where ideally they will engraft and remodel the damaged tissue into healthy tissue. However, numerous obstacles stand in the way of this regenerative technology becoming reality. Perhaps the greatest obstacle is that cells injected into many tissues are rapidly cleared via the lymphatics or vascular drainage. Cells that remain in the tissues face additional challenges related to inflammation and survival. Those cells that survive these challenges will not be fully capable of tissue regeneration unless they integrate appropriately into the damaged tissue via complex mechanisms that involve proliferation, differentiation, integration and communication with native cells and matrix. New technologies that can overcome any or all of these obstacles have great potential for improving treatment of many diseases including heart disease, diabetes, cancer, and Parkinson's disease, to name but a few. Affinergy has developed a generalized approach for engrafting therapeutic cells that makes use of target-specific modular bi-functional peptides termed interfacial biomaterials (IFBM's). Affinergy's IFBM's are designed to bind therapeutic biologic agents (cells, serum proteins, growth factors, etc.) to native surfaces (cells, extracellular matrix, tissue-specific proteins, etc.). We believe that Affinergy peptide linkers can be pre-incubated with therapeutic cells to accomplish the following goals: 1) inducing limited clustering of therapeutic cells to generate aggregates that are too large for lymphatic clearance; 2) inducing adhesion of injected cells to native cells and matrix components; 3) providing pro-survival signals to injected cells that will tend to increase their tissue survival and proliferation; and 4) targeting injected cells to tissue microenvironments that are most compatible with engraftment and survival. The goal of this Phase I SBIR proposal is to validate an IFBM approach to enhance engraftment of skeletal muscle myoblasts (SMM) after injection into cardiac muscle. In Phase II, we plan to test an optimized mixture of Affinergy peptides for therapeutic cell engraftment and functional tissue repair in animal models of disease. We have chosen engraftment of myoblasts as our initial proof of principle focus because they have been extensively studied in preclinical and clinical trials for the treatment of damaged myocardium and skeletal muscles. However, Affinergy's modular IFBM peptides developed for myoblast engraftment can be retooled for engraftment of other cell types into other tissues, leading to greatly improved cell engraftment strategies that will support regenerative cell therapy across numerous human diseases.

描述（由申请人提供）：理论上可以通过将健康或工程细胞注射到受损组织中来治疗许多人类疾病，理想情况下，它们将移植并重塑受损组织为健康组织。然而，许多障碍阻碍了这种再生技术成为现实。也许最大的障碍是，注射到许多组织中的细胞通过血管或血管引流迅速清除。留在组织中的细胞面临着与炎症和生存相关的额外挑战。在这些挑战中存活下来的那些细胞将不能完全进行组织再生，除非它们通过复杂的机制适当地整合到受损组织中，所述复杂的机制涉及增殖、分化、整合以及与天然细胞和基质的通讯。能够克服任何或所有这些障碍的新技术在改善许多疾病的治疗方面具有巨大的潜力，包括心脏病、糖尿病、癌症和帕金森病等。 Affinergy开发了一种通用的移植治疗细胞的方法，该方法利用称为界面生物材料（IFBM）的靶向特异性模块化双功能肽。Affinergy的IFBM设计用于结合治疗性生物制剂（细胞、血清蛋白、生长因子等）。天然表面（细胞、细胞外基质、组织特异性蛋白质等）。我们相信，Affinergy肽接头可以与治疗性细胞一起预孵育以实现以下目标：1）诱导治疗性细胞的有限聚集以产生对于淋巴清除来说太大的聚集体; 2）诱导注射的细胞与天然细胞和基质组分的粘附; 3）向注射的细胞提供将倾向于增加其组织存活和增殖的促存活信号;和4）将注射的细胞靶向与移植和存活最相容的组织微环境。该I期SBIR提案的目标是验证IFBM方法，以增强骨骼肌成肌细胞（SMM）注入心肌后的植入。在第二阶段，我们计划在动物疾病模型中测试Affinergy肽的优化混合物，用于治疗性细胞植入和功能性组织修复。我们选择成肌细胞的植入作为我们的主要焦点的初步证据，因为它们已经在临床前和临床试验中被广泛研究，用于治疗受损的心肌和骨骼肌。然而，Affinergy为成肌细胞移植开发的模块化IFBM肽可以重新组合，用于将其他细胞类型移植到其他组织中，从而大大改善细胞移植策略，支持多种人类疾病的再生细胞治疗。