Engineered Delivery of Adult Versus Fetal Stem Cells for Bone Regeneration

用于骨再生的成人干细胞与胎儿干细胞的工程化输送

基本信息

批准号：
7731072
负责人：
ROBERT E GULDBERG
金额：
$ 66.26万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
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：
2009-09-09 至 2011-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7731072
关键词：
Adult Affect Age Alginates Amniotic Fluid Arts Beds Biocompatible Materials Biomechanics Biomedical Engineering Biomimetics Bone Marrow Bone Regeneration Cell Survival Cell Therapy Cell-Matrix Junction Cells Clinical Trials Collagen Complement Consultations Cookbook Cues Data Defect Detection Development Developmental Biology Diagnostic radiologic examination Dose Effectiveness Engineering Enzyme-Linked Immunosorbent Assay Exposure to Fetal Tissues Functional Imaging Funding Mechanisms Gene Expression Gene Expression Regulation Gene Proteins Genes Glycocalyx Human Human Development Image Implant In Vitro Infection Injury Institutes Label Location Luciferases Magic Marrow Measures Mediating Methods Modeling Modification Molecular Profiling Mus Musculoskeletal Natural regeneration Nature Nude Rats Osseointegration Osteogenesis Outcome Measure Outcome Study Pain Pathway interactions Patients Peptides Phenotype Population Principal Investigator Procedures Production Protein Biosynthesis Protocols documentation Rattus Recipe Regenerative Medicine Relative (related person)Reporter Genes Research Reverse Transcriptase Polymerase Chain Reaction Running Signal Transduction Site Source Staging Stem cells Supporting Cell Surface System Technology Testing Texas Time Tissue Engineering Tissues Translating Transplantation Vertebral column Western Blotting Work Wound Healing adult stem cell adult stem cell transplantation amniotic fluid derived stem cell base bone bone morphogenetic protein 2 cell motility cell type clinically relevant design design and construction disability embryonic stem cell experience fetal fetal stem cell forest human stem cells implantation improved in vivo in vivo Model injured insight interdisciplinary approach interest luminescence migration mimetics mineralization multidisciplinary nanofiber nonhuman primate novel novel therapeutics osteogenic polycaprolactone programs public health relevance regenerative regenerative therapy repaired research study response to injury scaffold stem cell biology stem cell population tissue regeneration

Adult Affect Age Alginates Amniotic Fluid Arts Beds Biocompatible Materials Biomechanics Biomedical Engineering Biomimetics Bone Marrow Bone Regeneration Cell Survival Cell Therapy Cell-Matrix Junction Cells Clinical Trials Collagen Complement Consultations Cookbook Cues Data Defect Detection Development Developmental Biology Diagnostic radiologic examination Dose Effectiveness Engineering Enzyme-Linked Immunosorbent Assay Exposure to Fetal Tissues Functional Imaging Funding Mechanisms Gene Expression Gene Expression Regulation Gene Proteins Genes Glycocalyx Human Human Development Image Implant In Vitro Infection Injury Institutes Label Location Luciferases Magic Marrow Measures Mediating Methods Modeling Modification Molecular Profiling Mus Musculoskeletal Natural regeneration Nature Nude Rats Osseointegration Osteogenesis Outcome Measure Outcome Study Pain Pathway interactions Patients Peptides Phenotype Population Principal Investigator Procedures Production Protein Biosynthesis Protocols documentation Rattus Recipe Regenerative Medicine Relative (related person)Reporter Genes Research Reverse Transcriptase Polymerase Chain Reaction Running Signal Transduction Site Source Staging Stem cells Supporting Cell Surface System Technology Testing Texas Time Tissue Engineering Tissues Translating Transplantation Vertebral column Western Blotting Work Wound Healing adult stem cell adult stem cell transplantation amniotic fluid derived stem cell base bone bone morphogenetic protein 2 cell motility cell type clinically relevant design design and construction disability embryonic stem cell experience fetal fetal stem cell forest human stem cells implantation improved in vivo in vivo Model injured insight interdisciplinary approach interest luminescence migration mimetics mineralization multidisciplinary nanofiber nonhuman primate novel novel therapeutics osteogenic polycaprolactone programs public health relevance regenerative regenerative therapy repaired research study response to injury scaffold stem cell biology stem cell population tissue regeneration

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项目摘要

DESCRIPTION (provided by applicant): The robust regeneration potential of fetal tissue suggests that developmental biology may help guide strategies for tissue regeneration in adults. Decreases in regenerative capacity post-utero and with increasing age are likely due to multiple factors, however one important contributor may be changes in the availability and functionality of stem cells responsible for mounting a reparative response to injury. The overall objectives of this Bioengineering Research Partnership are to characterize and quantitatively compare the relative regenerative capacity of stem cells isolated from two distinct stages of human development (fetal and adult) and assess the effectiveness of different strategies for delivering stem cells for bone regeneration. The central hypothesis governing this research is that augmenting the number of viable stem cells at the injury site and promoting their reparative phenotype will significantly enhance functional repair of bone defects and spine fusion in a developmental stage dependent manner. To test this hypothesis, the multidisciplinary team will integrate stem cell biology with tissue engineering principles and well-established, quantitative test bed models. The approach will employ customized gene array analysis to elucidate differential gene regulation pathways of stem cells derived from amniotic fluid and adult bone marrow at baseline and during osteogenic differentiation. Composite scaffold and nanofiber mesh biomaterials technologies will be evaluated for their ability to effectively deliver stem cells for segmental defect repair and spine fusion. Finally, a novel biomimetic coating technology will be investigated as a means to program delivered stem cells towards the osteogenic phenotype. The proposed research is unique in that there has been very little to no previous research on quantitatively comparing the regenerative capacity of different stem cell sources, particularly from distinct developmental stages. The expected outcome of these studies is the identification of an effective stem cell source and delivery protocol that may be rapidly translated into new therapeutic options for patients lacking adequate endogenous cell repair mechanisms. PUBLIC HEALTH RELEVANCE: Injured or degenerated musculoskeletal tissues are the most common cause of long-term pain and disability world-wide, motivating efforts to develop new tissue regenerative therapies. Using novel cell delivery approaches, this project will quantitatively compare the regenerative capacity of two non-embryonic stem cell sources from different developmental stages (fetal and adult) in the clinically relevant settings of large bone defects and spine fusion.

描述（由申请人提供）：胎儿组织的强大再生潜力表明，发育生物学可以帮助指导成人组织再生策略。 UTERO后再生能力的降低和随着年龄的增长可能是由于多种因素所致，但是重要的一个重要因素可能是负责安装对损伤的率反应的干细胞的可用性和功能变化。这种生物工程研究伙伴关系的总体目标是表征和定量比较从人类发育的两个不同阶段（胎儿和成人）分离出的干细胞的相对再生能力，并评估不同策略在骨骼再生中提供干细胞的有效性。统治这项研究的中心假设是，增加受伤部位的可行干细胞数量并促进其修复表型的数量将显着增强以发育阶段依赖性方式的骨缺损和脊柱融合的功能修复。为了检验这一假设，多学科团队将将干细胞生物学与组织工程原理和建立良好的定量测试床模型相结合。该方法将采用自定义的基因阵列分析来阐明基线和成骨分化期间源自羊水和成年骨髓的干细胞的差异基因调节途径。将评估复合支架和纳米纤维网状生物材料技术，以有效地输送干细胞进行节段缺陷修复和脊柱融合的能力。最后，将研究一种新型的仿生涂料技术，以作为将干细胞传递到成骨表型的手段。拟议的研究是独一无二的，因为几乎没有关于定量比较不同干细胞来源的再生能力的研究，尤其是从不同的发育阶段进行比较。这些研究的预期结果是鉴定有效的干细胞源和递送方案，该方案可能会迅速转化为缺乏足够内源细胞修复机制的患者的新治疗选择。公共卫生相关性：受伤或退化的肌肉骨骼组织是全球长期疼痛和残疾的最常见原因，激励着开发新的组织再生疗法的努力。使用新型的细胞递送方法，该项目将定量比较来自大骨缺陷和脊柱融合的临床相关环境中不同发育阶段（胎儿和成人）的两个非胚胎干细胞源的再生能力。