Hydrogels for hMSC delivery & engraftment

用于 hMSC 递送的水凝胶

• 批准号: 8916875
• 负责人: Andres J Garcia
• 金额: $ 14.26万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8916875
• 关键词: Adhesives; Animal Model; Biocompatible Materials; Bolus Infusion; Bone Regeneration; Bone Tissue; Cartilage; Cell Adhesion; Cell Count; Cell Survival; Cell Therapy; Cells; Clinical; Clinical Trials; Collagen; Culture Media; Defect; Drug Formulations; Engineering; Engraftment; Ethylene Glycols; Exhibits; Fibronectins; Gene Expression; Histocytochemistry; Home environment; Human; Hydrogels; Immunodeficient Mouse; Immunohistochemistry; Implant; Integrin Binding; Integrin-mediated Cell Adhesion Pathway; Integrins; Intervertebral disc structure; Ligands; Luciferases; Mechanics; Mesenchymal Stem Cells; Monitor; Musculoskeletal; Osseointegration; Osteocalcin; Osteogenesis; Outcome; Peptide Hydrolases; Peptides; Pre-Clinical Model; Radial; Rattus; Recombinants; Regenerative Medicine; Reporter; Research; Signal Transduction; Source; Specificity; Stem Cell Research; Stem cells; System; Testing; Tissue Engineering; Tissues; Transplantation; Variant; Vascular Endothelial Growth Factors; Vascularization; Work; base; bone; density; ethylene glycol; improved; in vivo; in vivo imaging; injured; innovation; mimetics; novel; osteoblast differentiation; osteogenic; paracrine; promoter; receptor; repaired; self-renewal

DESCRIPTION (provided by applicant): Mesenchymal stem cells (MSC) represent a promising cell source for regenerative medicine applications. Transplanted MSC enhance bone, cartilage, and intervertebral disc repair in pre-clinical models and initial clinical trials. Howevr, the engraftment of transplanted MSC is extremely low, and the beneficial effects are generally attributed to trophic/paracrine actions. The low engraftment and survival of transplanted MSC significantly limit these cell-based therapies in the repair of challenging, non-healing defects. A major hurdle to MSC survival and engraftment is the lack of appropriate bioactive delivery vehicles. The objective of this project is to engineer biofunctional hydrogels to direct human MSC (hMSC) survival, engraftment, and function. Our central hypothesis is that hydrogels presenting integrin-specific adhesive ligands will promote hMSC engraftment, osteogenesis, and bone repair. This work will establish bioactive cell delivery vehicles that enhance MSC survival, engraftment and function compared to existing synthetic matrices. Aim 1: Engineer hydrogels presenting integrin-specific adhesive ligands to direct hMSC fate commitment and differentiation. Aim 2: Evaluate the ability of integrin-specific hydrogels to promote hMSC survival, engraftment, and bone repair. Aim 3: Analyze the effects of VEGF co-delivery from hydrogels on hMSC engraftment and bone repair. The proposed research is innovative because it focuses on exploiting integrin binding specificity to control hMSC survival, engraftment and function for bone repair and integrates new in vivo imaging approaches. This work is expected to yield the following outcomes. First, we will determine the extent to which integrin-specific ligands regulate hMSC signaling, commitment and differentiation into osteogenic, adipogenic and chondrogenic lineages. We will also establish novel bioactive cell delivery vehicles that enhance MSC survival, engraftment and bone formation for improved bone repair. Finally, because of the transformative potential of MSC, this research will have broad significance and impact to many regenerative medicine applications.

描述（由申请人提供）：间充质干细胞（MSC）代表了再生医学应用的有希望的细胞来源。移植的MSC在临床前模型和初始临床试验中增强了骨，软骨和椎间盘修复。 HOWEVR，移植的MSC的植入极低，有益效应通常归因于营养/旁分泌作用。移植的MSC的低植入和存活显着限制了这些基于细胞的疗法，以修复具有挑战性的非治疗缺陷。一个 MSC生存和植入的主要障碍是缺乏适当的生物活性递送车。该项目的目的是设计生物功能性水凝胶来指导人类MSC（HMSC）生存，植入和功能。我们的中心假设是呈现整合素特异性粘合剂配体的水凝胶将促进HMSC植入，成骨和骨修复。这项工作将建立与现有合成矩阵相比，可以增强MSC生存，植入和功能的生物活性细胞输送车辆。目标1：呈现整联蛋白特异性粘合剂配体的工程师水凝胶指导HMSC命运承诺和分化。目标2：评估整联蛋白特异性水凝胶促进HMSC生存，植入和骨修复的能力。 AIM 3：分析水凝胶中VEGF共递送对HMSC植入和骨修复的影响。拟议的研究具有创新性，因为它重点是利用整合素的结合特异性来控制HMSC的生存，植入和骨修复功能，并整合了新的体内成像方法。预计这项工作将产生以下结果。首先，我们将确定整联蛋白特异性配体在多大程度上将HMSC信号传导，承诺和分化为成骨，脂肪生成和软骨谱系。我们还将建立新型的生物活性细胞输送车辆，以增强MSC存活，植入和骨形成以改善骨骼修复。最后，由于MSC的变革潜力，这项研究将对许多再生医学应用具有广泛的意义和影响。