Hydrogels for hMSC delivery & engraftment

描述（由申请人提供）：间充质干细胞（MSC）是再生医学应用中很有前途的细胞来源。移植的间充质干细胞在临床前模型和初步临床试验中增强骨、软骨和椎间盘修复。然而，移植的间充质干细胞的植入极低，其有益作用通常归因于营养/旁分泌作用。移植间充质干细胞的低植入率和存活率极大地限制了这些基于细胞的治疗方法在修复具有挑战性的、不可愈合的缺陷方面的应用。一个

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.