Interfacial Adapters for Improved Cell Delivery to Tissues

描述(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，理想情况下，他们将植入受损组织并将其重塑为健康组织。然而，许多障碍阻碍了这种可再生技术成为现实。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。那些在这些挑战中幸存下来的细胞将不能完全具有组织再生的能力，除非它们通过涉及增殖、分化、整合以及与自然细胞和基质沟通的复杂机制适当地整合到受损组织中。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，其中包括心脏病、糖尿病、癌症和帕金森氏症，仅举几例。 AffinEnergy已经开发出一种通用的移植治疗细胞的方法，这种方法利用被称为界面生物材料(IFBM)的靶向特定的模块化双功能多肽。AffinEnergy的IFBM旨在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)。我们认为，可以将亲和多肽连接物与治疗细胞预先孵育，以实现以下目标：1)诱导治疗细胞的有限聚集，以产生太大而无法清除淋巴的聚集体；2)诱导注射细胞与自然细胞和基质成分的粘连；3)向注射细胞提供有利于生存的信号，这将有助于增加它们的组织存活和增殖；以及4)将注射细胞靶向最适合植入和存活的组织微环境。这项第一阶段SBIR建议的目标是验证IFBM方法，以增强骨骼肌成肌细胞(SMM)在注射到心肌中后的植入。在第二阶段，我们计划在疾病的动物模型中测试一种优化的亲和肽混合物，用于治疗性细胞植入和功能性组织修复。我们选择成肌细胞植入作为我们主要关注的初步证据，因为它们已经在治疗受损的心肌和骨骼肌的临床前和临床试验中进行了广泛的研究。然而，AffinEnergy为成肌细胞植入而开发的模块化IFBM多肽可以进行重组，以将其他类型的细胞植入其他组织，从而大大改进细胞植入策略，从而支持多种人类疾病的再生细胞治疗。

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.