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Engineering of Vascularized Bone

血管化骨工程

基本信息

批准号：
8308943
负责人：
JEREMY J MAO
金额：
$ 55.69万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-25 至 2014-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8308943
关键词：
Adipose tissue Adult Allogenic Autologous Biocompatible Materials Biological Assay Biology Biomedical Engineering Blood Vessels Bone Development Bone Marrow Bone Marrow Aspiration Bone Substitutes Bone Tissue Bone Transplantation Caliber Calvaria Cell Density Cell Lineage Cell physiology Cells Chronic Disease Clinical Communities Connexin 43 Data Defect Dermal Development Dimensions Dose Endothelial Cells Engineering Excision Flow Cytometry Fluorescence Fluorescence-Activated Cell Sorting Goals Gold Growth Factor Healed Hematopoiesis Hematopoietic Stem Cell Transplantation Hematopoietic stem cells Histology Homeostasis Human Hydroxyapatites Immunohistochemistry In Vitro Mechanics Mediating Mesenchymal Stem Cell Transplantation Mesenchymal Stem Cells Modality Modeling Molecular Morbidity - disease rate Natural regeneration Nerve Nude Rats Operative Surgical Procedures Osteoblasts Osteocalcin Osteogenesis Outcome Outcome Measure Outpatients Platelet-Derived Growth Factor Polystyrenes Population Procedures Reporting Shapes Site Smooth Muscle Actin Staining Method Spectroscopy, Fourier Transform Infrared Stem cells Stromal Cells Structure Surgeon Testing Tissue Engineering Tissues Translations Transplantation Trauma Tubular formation Vascular Endothelial Growth Factors Vascularization Work analog angiogenesis base bone bone healing bone sialoprotein clinical practice clinically significant computerized controlled release expectation healing immunocytochemistry improved in vivo novel osteogenic osteopontin pathogen reconstruction scaffold skeletal stem tissue culture transmission process tumor

项目摘要

Project Summary Bone grafts are critically needed in the surgical reconstruction of skeletal defects resulting from trauma, chronic diseases, tumor removal and congenital anomalies. Bone tissue engineering offers tremendous potential in transforming the clinical practice of skeletal reconstruction. However, several critical barriers have restricted the translation of bone tissue engineering into clinical practice. Importantly, one of the key barriers in bone tissue engineering is not bone per se; instead, it is suboptimal vascularization. Emerging work from us and others has begun to explore an exciting cross-talk between two distinctive populations of stem/progenitor cells that generate bone and angiogenesis, namely mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs). Bioengineered angiogenesis by co-transplantation of HSCs and MSCs is a departure from current angiogenesis approaches including growth factor delivery or fabricating blood vessel analogs. In development, HSCs and MSCs function synergistically to induce (vascularized) osteogenesis. In the adult, MSCs co-reside with HSCs in bone marrow niches among other stromal cells that are the focus on intensifying studies. MSCs are conventionally isolated as adherent cells (to tissue culture polystyrene) by bone tissue engineering community, whereas non-adherent HSCs are conventionally discarded. Our preliminary data, as documented in a recent report in PloS One, demonstrate that co- transplantation of MSC and HSC lineages yielded vascularized ectopic bone, more significantly than the transplantation of MSC or HSC alone. These findings, and also recent discoveries of MSC-HSC cross-talk by others, have motivated our central hypothesis that co-transplanted MSCs and HSCs regenerate vascularized bone in an orthotopic model. The calvarial defect represents a widely utilized model for bone healing and substantial clinical challenges. Current bone substitutes such as hydroxyapatite and grafts are below the surgeon's expectations. Accordingly, the overall goal of this proposal is to engineer vascularized bone in vivo orthotopically from synergistic actions of HSCs and MSCs. Although co-transplantation of HSCs and MSCs represents a novel concept in bone tissue engineering, we believe that a great deal of fundamental biology needs to be understood, some of which are planned in this proposal, prior to the translation of this approach to clinical setting. An exciting potential that will be explored as our long-term goal is that MSCs and HSCs can be isolated in a single outpatient bone marrow aspiration procedure, and minimally manipulated to regenerate vasculature-dependent tissues such as bone, adipose, nerve and dermal grafts.

项目摘要骨移植是外科手术重建骨缺损所急需的，创伤、慢性疾病、肿瘤切除和先天性异常。骨组织工程提供了改变骨骼重建临床实践的巨大潜力。但几关键的障碍限制了骨组织工程向临床实践的转化。重要的是，骨组织工程中的关键障碍之一不是骨本身，而是次优血管化。我们和其他人的新兴工作已经开始探索一个令人兴奋的两种不同的生成骨的干/祖细胞群体之间的串扰，血管生成，即间充质干细胞（MSC）和造血干细胞（HSC）。通过HSC和MSC的共移植的生物工程化血管生成偏离了当前的血管生成方法包括生长因子递送或制造血管类似物。在在骨发育中，HSC和MSC协同作用以诱导（血管化）骨生成。在在成年人中，MSC与HSC共同存在于骨髓小生境中，而其他基质细胞是研究的重点。加强研究。MSC通常作为贴壁细胞分离（用于组织培养聚苯乙烯），而非粘附的HSC通常是丢弃。我们的初步数据，如最近在PLoS One上的一份报告所记录的，表明共同- MSC和HSC谱系的移植产生了血管化的异位骨， MSC或HSC单独移植。这些发现，以及最近发现的MSC-HSC 其他人的交叉讨论，激发了我们的中心假设，即共同移植的MSC和HSC 在原位模型中再生血管化骨。颅骨缺损代表了广泛的用于骨愈合和实质性临床挑战的模型。目前的骨替代品，如羟基磷灰石和移植物都低于外科医生的预期因此，这一总体目标一个建议是通过HSC和HSC的协同作用在体内原位工程化血管化骨， MSC。虽然HSC和MSC的共移植在骨组织中代表了一个新的概念，工程学，我们认为，大量的基础生物学需要理解，一些在将该方法转化为临床环境之前，在本提案中计划进行。一个作为我们的长期目标，将探索的令人兴奋的潜力是可以分离MSC和HSC，在一个单一的门诊骨髓抽吸过程中，血管依赖性组织，如骨、脂肪、神经和真皮移植物。