Interfacial Adapters for Improved Cell Delivery to Tissues

描述（由申请人提供）：理论上，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，在理想情况下，它们将植入并重塑受损组织为健康组织。然而，这种再生技术成为现实的道路上有许多障碍。也许最大的障碍是注入许多组织的细胞会通过淋巴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。那些在这些挑战中存活下来的细胞将不能完全具有组织再生能力，除非它们通过复杂的机制，包括增殖、分化、整合和与天然细胞和基质的交流，适当地融入受损组织。能够克服任何或所有这些障碍的新技术有很大的潜力来改善许多疾病的治疗，包括心脏病、糖尿病、癌症和帕金森病，仅举几例。

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.