TRABECULAR BONE-DERIVED CHONDROPROGENITOR CELLS

小梁骨来源的软骨祖细胞

• 批准号: 6632779
• 负责人: KEITH G DANIELSON
• 金额: $ 7.95万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6632779
• 关键词: biomarker; bone morphogenetic proteins; cartilage; cartilage development; cell differentiation; cell growth regulation; cell proliferation; chondrocytes; chondroitin sulfates; collagen; gene expression; human tissue; immunocytochemistry; mesenchyme; osteoblasts; polymerase chain reaction; proteoglycan; substantia spongiosa; thyroxine; tissue /cell culture; transforming growth factors

DESCRIPTION (Taken from the application): Wound healing and fracture repair in adult bone proceed via callus formation and an endochondral ossification sequence, where newly formed cartilage proliferates, matures, and undergoes hypertrophy, and is eventually replaced by the new bone that bridges the fracture gap. During this process, chondro- and osteo-progenitor cells are recruited to the damaged tissue site and are induced to differentiate in a s-atiotemporal specific manner to give rise to the regenerate endochondral. These progenitor cells are thought to be derived from local (not hematogenous) sources, i.e. they represent endogenous cell populations within the adult bony skeleton. While there is strong evidence that the bone marrow stroma and the periosteum both contain mesenchymal progenitor cells, our working hypothesis in this application is that multipotent progenitor cells, such as chondroprogenitor cells, are in fact also localized within the osteoid matrix of adult mature bone. This hypothesis is supported by our preliminary results that cells isolated from explants of fragments of adult human trabecular bone, traditionally denoted as "osteoblast-like cells", can be induced to differentiate into chondrocyte-like cells when maintained as an aggregate pellet culture, and secrete a sulfated proteoglycan-rich matrix containing collagen type I1. This induction of chondrogenesis is enhanced by factors such as transforming growth factor (TGF)-Bi or bone morphogenetic protein-2 (BMP-2), which have previously been shown to promote chondrogenesis in embryonic mesenchymal cells. We propose that these osteoblastic cells may represent a previously unrecognized population of multipotential mesenchymal progenitor cells. The Specific Aims are: 1 ) To identify and isolate chondroprogenitor cells from adult human trabecular bone; 2) To characterize the differentiation program of bone-derived chondroprogenitor cells; and 3) To determine the plasticity of the chondrogenic activity of bone-derived chondroprogenitor cells. Completion of these studies should clarify the characteristics and regulation of differentiation of a novel, chondroprogenitor cell population. This research will also determine if these adult trabecular bone-derived cells may serve as a progenitor cell source for cartilage engineering and repair.

描述（取自应用程序）：伤口愈合和断裂修复 成人骨骼通过愈伤组织形成和内软骨骨化进行 序列，新形成的软骨增殖，成熟和经历 肥大，最终被桥接的新骨所取代 断裂间隙。在此过程中，软骨和骨 - 促进蛋白细胞是 招募到受损的组织部位，并诱使在A中区分 S-静脉特定方式产生再生内软骨。 这些祖细胞被认为是从局部衍生的（不是血源） 来源，即它们代表成年骨内的内源细胞群 骨骼。虽然有充分的证据表明骨髓基质和 骨膜都包含间充质祖细胞，我们在 该应用是多能祖细胞，例如 实际上，软骨元素细胞也位于骨质基质中 成人成熟的骨头。我们的初步结果支持了这一假设 从成年人类小梁骨碎片外植体中分离出来的细胞， 传统上称为“成骨细胞样细胞”，可以诱导 当保持为骨料时，分化为软骨细胞样细胞 颗粒培养，并分泌含有富含蛋白聚糖的富含蛋白聚糖的基质 胶原型I1。这种软骨发生的诱导是通过此类因素增强的 作为转化生长因子（TGF）-BI或骨形态发生蛋白-2（BMP-2）， 以前已显示出来促进胚胎中的软骨发生 间充质细胞。我们建议这些成骨细胞可能代表 以前未认可的多能性间充质祖细胞 细胞。具体目的是：1）识别和分离软骨源 来自成年人类小梁骨的细胞； 2）表征差异化 骨衍生的软骨源细胞的程序； 3）确定 骨源性软骨元基因软骨活性的可塑性 细胞。这些研究的完成应阐明特征和 调节新型软骨元素细胞种群的分化。 这项研究还将确定这些成年小梁骨衍生的细胞是否 可以用作软骨工程和维修的祖细胞来源。