Development of a Mammalian Model for Rib Repair

肋骨修复哺乳动物模型的开发

• 批准号: 8739147
• 负责人: Francesca V Mariani
• 金额: $ 17.48万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-23 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8739147
• 关键词: Adult; Amphibia; Autologous; Back; Basic Science; Biological; Bone Regeneration; Bone Transplantation; Cartilage; Cells; Communities; Connective Tissue; Defect; Development; Excision; Face; Generations; Genetic; Goals; Healed; Human; In Vitro; Individual; Injury; Left; Location; Mammals; Mediating; Mesenchymal Stem Cells; Methods; Modeling; Molecular; Molecular Profiling; Mus; Natural regeneration; Operative Surgical Procedures; Oryctolagus cuniculus; Pathway interactions; Patients; Periosteum; Physiological; Process; Property; Rest; Site; Skeleton; Source; Speed; Stem cells; Study models; Surgeon; Time; Transgenic Mice; Translating; Visit; appendage; base; bone; bone healing; cartilage repair; cell type; expectation; healing; in vivo; mouse model; mutant; progenitor; public health relevance; reconstruction; repaired; response; rib bone structure; skeletal; skeletal injury; skeletal regeneration; skeletal tissue; substantia spongiosa

DESCRIPTION (provided by applicant): The skeleton provides a rigid, protective frame for the rest of the body and large injuries or defects can be incapacitating. In particular, the treatment f segmental defects remains an unresolved problem today. Autogenous bone graft is limited in supply and the biological activity of bone graft substitutes requires further refinement. Thus, new strategies for more physiological healing of critical sized bone defects are much needed. Studying models for bone regeneration in small mammals is a vital first step to developing treatments for severe skeletal injuries. Although humans do not repair as well as amphibians, human adults demonstrate a remarkable ability to regenerate large portions of the rib (>6 inches). We have developed a mouse model for rib repair that is amenable to genetic and surgical manipulation. Our preliminary studies have shown that 1) complete repair occurs within 1-2 months, 2) regrowth occurs in the middle of the resection site as well as from the ends, and 3), that the presence of the surrounding connective tissue sheath, or periosteum, is required for complete healing to occur. Based on our preliminary findings we now aim 1) to determine what steps occur to build new bone with the expectation that a rapidly produced cartilage intermediate is key and 2) to determine if the cells involved in the repair arise from progenitors in the periosteum. Our ultimate goal is to harness the unique features of rib skeletal repair to develop methods for enhancing bone healing in other locations of the body.

描述（由申请人提供）：骨骼为身体的其他部分提供了一个刚性的保护框架，大的损伤或缺陷可能会使人丧失能力。特别是，节段性缺损的治疗至今仍是一个未解决的问题。自体骨移植物的供应有限，骨移植替代物的生物活性需要进一步改进。因此，新 非常需要用于临界尺寸骨缺损的更生理愈合的策略。研究小型哺乳动物的骨再生模型是开发严重骨骼损伤治疗方法的重要第一步。虽然人类的修复能力不如两栖动物，但成年人表现出了非凡的能力，可以再生大部分肋骨（>6英寸）。我们已经开发了一种小鼠模型，肋骨修复，是经得起遗传和手术操作。我们的初步研究表明：1）完全修复发生在1-2个月内，2）再生发生在切除部位的中间以及末端，3）周围结缔组织鞘或骨膜的存在是完全愈合所必需的。根据我们的初步发现，我们现在的目标是1）确定建立新骨需要采取哪些步骤，并期望快速产生的软骨中间体是关键，2）确定参与修复的细胞是否来自骨膜中的祖细胞。我们的最终目标是利用肋骨骨骼修复的独特功能来开发增强身体其他部位骨愈合的方法。

项目成果

A surgical procedure for resecting the mouse rib: a model for large-scale long bone repair.

切除小鼠肋骨的外科手术：大规模长骨修复的模型。

• 发表时间: 2015
• 期刊: Journal of visualized experiments : JoVE
• 作者: Tripuraneni,Nikita;Srour,MarissaK;Funnell,JohnW;Thein,ThuZanTun;Mariani,FrancescaV
• 通讯作者: Mariani,FrancescaV

Updated embryology of the upper limb.

更新了上肢的胚胎学。

• DOI: 10.1016/j.jhsa.2014.01.048
• 发表时间: 2014
• 期刊: The Journal of hand surgery
• 作者: Vogeli,KevinM;Mariani,FrancescaV;Lightdale,Nina
• 通讯作者: Lightdale,Nina

Prkci is required for a non-autonomous signal that coordinates cell polarity during cavitation.

• DOI: 10.1016/j.ydbio.2016.06.002
• 发表时间: 2016-08-01
• 期刊: Developmental biology
• 影响因子: 2.7
• 作者: Mah IK;Soloff R;Izuhara AK;Lakeland DL;Wang C;Mariani FV
• 通讯作者: Mariani FV