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.

项目摘要在骨骼缺陷的手术重建中，骨移植是至关重要的创伤，慢性疾病，肿瘤清除和先天异常。骨组织工程提供改变骨骼重建的临床实践方面的巨大潜力。但是，有几个关键障碍限制了将骨骼组织工程的翻译成临床实践。重要的是，骨组织工程的关键障碍之一本身不是骨头。相反，是次优血管化。来自我们和其他人的新兴工作已经开始探索令人兴奋的在产生骨骼和血管生成，即间充质干细胞（MSC）和造血干细胞（HSC）。通过HSC和MSC的共转移，生物工程的血管生成是与电流偏离的血管生成方法，包括生长因子递送或制造血管类似物。在开发，HSC和MSC协同诱导（血管化）成骨。在成人，MSC与HSC在骨髓壁ches中共同居住在其他基质细胞中，这是焦点关于加强研究。通常将MSC作为粘附细胞分离（到组织培养聚苯乙烯）通过骨组织工程社区，而非遵守HSC是常规的丢弃。正如PLOS One最近的一份报告中所记录的那样，我们的初步数据表明 MSC和HSC谱系的移植产生的血管化异位骨，比单独的MSC或HSC的移植。这些发现，以及MSC-HSC的最新发现其他人的交叉讲话激发了我们共同移植MSC和HSC的中心假设在原位模型中再生血管化骨。钙钙缺陷代表一个广泛的利用模型用于骨骼愈合和实质性的临床挑战。当前的骨骼替代品，例如羟基磷灰石和移植物低于外科医生的期望。因此，总体目标提案是从HSC和 MSC。尽管HSC和MSC的共转移代表了骨组织中的一个新概念工程学，我们认为需要了解很多基本生物学，其中一些在将这种方法转换为临床环境之前，这是在此提案中计划的。一个令人兴奋的潜力将被探索为我们的长期目标是MSC和HSC可以隔离在单一门诊骨髓抽吸程序中，并最少操纵以再生血管依赖性组织，例如骨骼，脂肪，神经和皮肤移植物。