权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Enhancing the potency of aged adult stem cells for tissue reconstruction

增强老年成体干细胞用于组织重建的效力

基本信息

批准号：
10229598
负责人：
Michal Zalzman
金额：
$ 32.97万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10229598
关键词：
3-Dimensional 3D Print Adult Aging Biological Assay Biopsy Bioreactors Bone Density Bone Diseases Bone Regeneration Bone Transplantation Cadaver Cell Differentiation process Cell Extracts Cell Line Cell Proliferation Cell Survival Cells Chromatin Clinical DNA Data Defect Embryo Engraftment Fluorescence Anisotropy Future Gene Expression Regulation Generations Goals Harvest Histologic Human In Vitro Individual Injury Laboratories Lead Long-Term Effects Mandible Mediating Medical Device Mesenchymal Differentiation Mesenchymal Stem Cells Methods Morbidity - disease rate Mus Musculoskeletal Operative Surgical Procedures Osteoblasts Osteogenesis Patients Perfusion Pharmaceutical Preparations Phenotype Physical condensation Physiological Proteins Protocols documentation RNA Recombinants Reconstructive Surgical Procedures Regenerative Medicine Regulation Reproducibility Role Stem Cell Factor Techniques Technology Telomere Shortening Teratoma Testing Therapeutic Tissue Engineering Tonsil Undifferentiated adult stem cell aged base bone bone cell bone engineering bone quality c-myc Genes cell age chromatin remodeling clinical application design embryonic stem cell high throughput screening in vivo induced pluripotent stem cell innovation loss of function microCT millimeter monolayer novel nuclear reprogramming operation preservation progenitor reconstruction regenerative approach repaired restoration scaffold scale up self-renewal stem stem cell biomarkers stem cell differentiation stem cell survival stem cells stemness success telomere tissue reconstruction tissue stem cells transcriptome sequencing

项目摘要

ABSTRACT More than half a million patients undergo surgeries to repair of large bony defects every year. However, the two primary options currently available for bone reconstruction are the use of bone harvested from the patient suffering from the injury by additional surgeries, or bone grafts from cadaver donors. However, these multiple operations incur significant morbidity on the patient. Thus, bone engineering offers an attractive alternative approach for regenerative medicine. Mesenchymal stem cells (MSCs) have a great potential for engineering bone grafts and have been shown to generate bone cells in-vitro in three dimensional (3D) scaffolds. However, the therapeutic application of human MSCs in bone regeneration and reconstruction is still limited by a physiological aging related decline in their differentiation potential, compromising the feasibility and reproducibility of therapies. Moreover, bone grafts generated from MSCs are only millimeters in size limiting their use in a clinical setting. Telomere shortening restricts cell proliferation and ultimately leads to in-vitro aging and loss of function. We have designed a highly innovative approach, to overcome these challenges based on preliminary data from our laboratory showing that the differentiation potency of aged MSCs can be restored by the factor ZSCAN4. Our overall goal is to design novel protocols generate bone grafts suitable for the treatment of degenerative bone diseases and bone reconstructive surgeries. In this application we will a. Establish a clinically scaled bone graft from tonsil derived human MSCs. b. Define the effects of ZSCAN4 on bone differentiation potential of aged and in vitro aged MSCs as a mean to allow the scalability to human bone size requirements. c. Determine the role of ZSCAN4 in regulation of stemness potency.

摘要每年有50多万患者接受手术修复大面积骨缺损。然而，目前可用于骨重建的两种主要选择是使用骨通过额外的手术从遭受损伤的患者身上获取，或者从尸体捐赠者然而，这些多个操作对患者造成显著的发病率。因此，在本发明中，骨工程为再生医学提供了一种有吸引力的替代方法。充质干细胞（MSC）具有用于工程化骨移植物的巨大潜力，在三维（3D）支架中体外产生骨细胞。然而，治疗应用人MSC在骨再生和重建中的作用仍然受到生理老化的限制相关的下降，他们的分化潜力，损害的可行性和再现性，治疗此外，由MSC生成的骨移植物的尺寸仅为毫米，限制了它们的使用在临床环境中。端粒缩短限制细胞增殖并最终导致体外老化和功能丧失。我们设计了一种高度创新的方法，以克服这些问题。基于我们实验室的初步数据的挑战表明，老化的MSC可以通过因子ZSCAN4恢复。我们的总体目标是设计新颖的协议产生适合于治疗退行性骨疾病和骨重建手术。在这个应用程序中，我们将A。建立临床规模的骨移植物，扁桃体来源的人MSC。B.确定ZSCAN 4对老年人骨分化潜力的影响和体外老化的MSC作为允许可扩展性以满足人骨尺寸要求的手段。C. 确定ZSCAN4在调节干性效价中的作用。