BM SUBPOPULATIONS TO REPAIR HUMAN ISLET INJURY AND SUPPORT ITS LONGEVITY

BM 亚群修复人类胰岛损伤并支持其长寿

• 批准号: 8167643
• 负责人: LUGUANG LUO
• 金额: $ 12.17万
• 依托单位: ROGER WILLIAMS HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167643
• 关键词: ATP Receptors; Bone Marrow; Cell Death; Cells; Coculture Techniques; Computer Retrieval of Information on Scientific Projects Database; Functional disorder; Funding; Grant; Growth; Human; In Vitro; Injury; Institution; Insulin; Interleukin-1 beta; Islet Cell; Islets of Langerhans Transplantation; Lead; Longevity; Marrow; Myocardium; NOD/SCID mouse; Natural regeneration; Neurons; Pathway interactions; Process; Protocols documentation; Research; Research Personnel; Resources; Skin; Solutions; Source; Tissues; Transplantation; United States National Institutes of Health; Vascularization; extracellular; in vivo; insight; islet; receptor; reconstitution; repaired; success

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There has been no change in the scope of this project. The success of islet transplantation is hampered by the high rate of islet cell death and dysfunction after isolation. Therefore, the repair of islet damage from the isolation process and the opportunity to maintain islets long term in vitro as a new islet resource would represent significant advances and lead to a more widespread use of islet cell transplantation. Successful utilization of bone marrow in repairing skin, neuron, heart, and muscle injury led us to propose that bone marrow could offer a potential solution to these challenges. In our preliminary studies using co-cultures of whole bone marrow with islet, bone marrow was shown to increase islet function/survival (more than six months), stimulate islet growth and generate long-term insulin producing tissue in vitro. We hypothesize that specific subpopulations of marrow cells may be responsible for these findings. We have also hypothesized that extracellular ATP, ATP receptor (purinoreceptor P2XR), and interleukin 1beta (IL-1beta) are involved in bone marrow-induced repair of islet injury. In this project, we plan to identify whether multiple or single specific lineage marrow cells contribute to islet reconstitution. We will examine whether these reconstituted islets have sufficient function and vascularization in vivo as determined by transplantation into NOD/SCID mice. Finally, we will investigate whether bone marrow modulates ATP, its receptor P2XR, IL-1¿ and its downstream pathways. This project will have benefits for current islet transplantation protocols and will provide insight into the mechanisms of islet cell death and regeneration.

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