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Cellular Contribution to Bone Healing

细胞对骨愈合的贡献

基本信息

批准号：
7236923
负责人：
CELINE I COLNOT
金额：
$ 7.67万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-06-01 至 2008-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7236923
关键词：
biological signal transduction bone bone development bone disorder cell cell interaction cell differentiation cellular pathology embryogenesis histology immunocytochemistry in situ hybridization laboratory mouse normal ossification periosteums regeneration stem cells wound healing

项目摘要

DESCRIPTION (provided by applicant): My long-term goals are to understand the cellular and molecular mechanisms regulating bone formation during skeletogenesis in the embryo and during repair of injured bone in the adult. The adult skeleton has a remarkable potential to heal by forming new bone that is indistinguishable from adjacent, uninjured tissues. Aspects of this adult regenerative process resemble skeletal development during fetal life. However, differences exist between the fetal developmental program and the adult regenerative process, such as the sources of skeletal stem cells. The origins of adult skeletal stem cells and their cellular and molecular contributions to skeletal tissue regeneration remain under appreciated. The goal of the work outlined in this proposal is to assess the extent to which skeletal stem cells residing in the periosteum (the tissue at the outer surface of bone) and endosteum (the tissue at the inner surface of bone) contribute differently to intramembranous and endochondral ossification during bone repair. Aim 1 will compare the mechanisms of bone healing in the periosteum and endosteum, by analyzing the distinct cellular and molecular responses after creating periosteal or endosteal injuries. Aim 2 will develop a new lineage analysis approach in order to determine the cellular contribution of the periosteum and endosteum during healing via intramembranous and endochondral ossification. This approach will be based on bone grafting experiments, which will allow me to distinguish periosteal- and endosteal-derived cells during healing. Aim 3 will assess the extent to which the healing responses of the periosteum and endosteum are intrinsic to each tissue or whether the microenvironment influences cell differentiation. To do so, bone grafts containing periosteal or endosteal stem cells will be ectopically transplanted and the contribution of these stem cells to bone healing will be analyzed. These experiments will be essential to develop new approaches to elucidate the role of osteogenic and chondrogenic factors on different stem cell populations within the bone. This research will have a direct impact on tissue engineering, which aims to use combinations of stem cells with osteoinductive and osteoconductive materials to improve the treatment of delayed fracture healing and bone diseases.

描述（由申请人提供）：我的长期目标是了解胚胎骨骼发生过程中和成人损伤骨修复过程中调节骨形成的细胞和分子机制。成年人的骨骼具有显著的愈合潜力，可以通过形成与邻近的未受伤组织难以区分的新骨来愈合。这种成人再生过程的各个方面类似于胎儿时期的骨骼发育。然而，胎儿发育程序和成人再生过程之间存在差异，例如骨骼干细胞的来源。成体骨骼干细胞的起源及其对骨骼组织再生的细胞和分子贡献仍未得到充分认识。本提案中概述的工作目标是评估驻留在骨膜（骨外表面的组织）和骨内膜（骨内表面的组织）中的骨骼干细胞在骨修复过程中对膜内和软骨内骨化的不同贡献程度。目的1通过分析骨膜或骨内膜损伤后不同的细胞和分子反应，比较骨膜和骨内膜骨愈合的机制。目的2将开发一种新的谱系分析方法，以确定愈合过程中骨膜和骨内膜通过膜内和软骨内骨化的细胞贡献。这种方法将基于骨移植实验，这将使我能够在愈合过程中区分骨膜和骨内膜来源的细胞。目的3将评估骨膜和骨内膜的愈合反应在多大程度上是每个组织固有的，或者微环境是否影响细胞分化。为此，将异位移植含有骨膜或骨内膜干细胞的骨移植物，并分析这些干细胞对骨愈合的贡献。这些实验将是必不可少的，以开发新的方法来阐明骨和软骨形成因子对不同的干细胞群在骨中的作用。这项研究将对组织工程产生直接影响，组织工程旨在使用干细胞与骨诱导和骨传导材料的组合来改善延迟骨折愈合和骨骼疾病的治疗。