MSC Encapsulation with Thin Gel Coating

具有薄凝胶涂层的 MSC 封装

• 批准号: 9383973
• 负责人: David J Mooney
• 金额: $ 68.53万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9383973
• 关键词: Address; Alginates; Biocompatible Materials; Blood Circulation; Cell Survival; Cell Therapy; Cell Transplantation; Cell Transplants; Cell physiology; Cells; Cellular biology; Chemicals; Clinical; Clinical Trials; Devices; Disease; Effectiveness; Encapsulated; Gel; Goals; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Hydrogels; Infusion procedures; Injectable; Intra-Arterial Infusions; Intravenous; Intravenous infusion procedures; Life; Mesenchymal Stem Cells; Microfluidics; Myocardial Infarction; Outcome; Patients; Process; Property; Proteins; Rodent Model; Savings; Stem cells; Technology; Thinness; Time; Transplantation; Treatment Efficacy; United States National Institutes of Health; Work; base; chemical property; clinical application; clinically relevant; flexibility; graft vs host disease; improved; in vivo; intraperitoneal; new technology; novel strategies; paracrine; particle; physical property; preclinical study; research clinical testing; scale up; stem cell biology; success; tool; viscoelasticity; web site

Mesenchymal stem cell (MSC) therapies are currently in widespread clinical testing for a number of diseases, but a common theme of trials to date is the massive loss of the MSCs following transplantation. This outcome likely relates to the approach utilized for delivery – clinical trials typically utilize intravenous (iv) infusion of suspended cells. In contrast, encapsulation of cells in various materials has been widely explored in preclinical studies to enhance transplanted cell survival, but the resulting particles and devices have been too large to allow iv infusion, providing a significant practical obstacle to their clinical implementation. Further, as the bioactivity of MSCs is now widely ascribed to paracrine secretions, control over the secretome of the cells following transplantation may be crucial to their clinical success. We recently developed a highly efficient microfluidic process to encapsulate single cells in a very thin layer of hydrogel (~ 5 microns); this thin coating still allows cells to be infused intravenously, but dramatically increases both their survival and the duration of their secreted products in the bloodstream. We hypothesize this technology will provide a timely new tool for MSC therapies and dramatically expand their clinical utility. Here, we propose to further develop this new technology, and to study its utility in context of hematopoietic stem cell therapy (HSCT). We have put together a unique team to address the hypothesis underlying this project, with leaders in microfluidics technology (Weitz), biomaterials (Mooney), and hematopoietic stem cell (HSC) biology and HSCT (Scadden). We will pursue our objectives by: (1) Tune the chemical and physical properties of microgels, and scale-up the microfluidics technology to enable clinically relevant numbers of MSCs to be encapsulated with high efficiency, (2) Determine how MSC persistence and paracrine secretions following transplantation can be tuned, both qualitatively and quantitatively, by the chemical and physical properties of the encapsulating alginate hydrogel, and (3) Study the impact of gel-encapsulated MSCs, following intravenous infusion, on the treatment of graft versus host disease (GVHD) following HSCT in a rodent model. At the completion of these studies we will have validated the effectiveness and practicality of this approach to MSC therapy. Importantly, the results of these studies will help to define how the MSC secretome impacts the effectiveness of MSCs in GVHD, and the importance of immunoprotection of the MSCs following transplantation. Further, this approach is also likely to be broadly useful to the wide array of other clinical applications of MSCs and to the use of many other types of stem cells.

间充质干细胞（MSC）疗法目前在许多疾病的广泛临床试验中，