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）：从理论上讲，许多人类疾病可以通过将健康或工程细胞注射到受损组织中来治疗，理想情况下它们将植入并重塑受损的组织中并重塑其健康组织。但是，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，注入许多组织的细胞通过淋巴管或血管排水迅速清除。保留在组织中的细胞面临与炎症和存活有关的其他挑战。那些在这些挑战中生存的细胞将无法完全能够组织再生，除非它们通过涉及增殖，分化，整合和与天然细胞和基质的复杂机制适当地整合到受损的组织中。可以克服任何或全部这些障碍的新技术具有改善许多疾病的治疗，包括心脏病，糖尿病，癌症和帕金森氏病，仅举几例。 Affinergy开发了一种用于植入治疗细胞的广义方法，该方法利用了称为界面生物材料（IFBM）的目标特异性模块化肽。 Affinergy的IFBM旨在将治疗生物学剂（细胞，血清蛋白，生长因子等）与天然表面（细胞，细胞外基质，组织特异性蛋白等）结合。我们认为，可以预先与治疗细胞预孵育以实现以下目标：1）诱导治疗细胞的聚类有限，以产生太大的淋巴清除率； 2）诱导注射细胞对天然细胞和基质成分的粘附； 3）向注射的细胞提供促生存信号，这些信号会增加其组织的存活和增殖； 4）将注射细胞靶向与植入和存活最兼容的组织微环境。该阶段I SBIR提案的目的是验证一种IFBM方法，以增强进入心脏肌肉后骨骼肌成肌细胞（SMM）的植入。在第二阶段，我们计划在疾病的动物模型中测试优化的掺假肽的优化混合物，以进行治疗性细胞植入和功能性组织修复。我们选择了成肌细胞的植入作为主要重点的最初证明，因为它们已经在临床前和临床试验中进行了广泛的研究，用于治疗受损的心肌和骨骼肌。然而，可以对Affinergy的模块化IFBM肽为子细胞植入植入，以植入其他细胞类型的其他组织，从而极大地改善了细胞植入策略，这些策略将支持许多人类疾病的再生细胞疗法。