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（摘自申请）：伤口愈合和骨折修复 成人骨通过愈伤组织形成和软骨内骨化进行 新形成的软骨增殖、成熟并经历 肥大，最终被桥接的新骨所取代 骨折间隙。在此过程中，软骨和骨祖细胞 被招募到受损的组织部位并被诱导分化 s-时空特定方式产生软骨内再生。 这些祖细胞被认为源自局部（而非血源） 来源，即它们代表成人骨内的内源细胞群 骨骼。虽然有强有力的证据表明骨髓基质和 骨膜都含有间充质祖细胞，我们的工作假设是 该应用是多能祖细胞，例如 软骨祖细胞，事实上也位于类骨基质内 成人成熟骨。我们的初步结果支持了这一假设 从成人小梁骨碎片的外植体中分离出的细胞， 传统上称为“成骨细胞样细胞”，可被诱导 当维持聚集体时分化成软骨细胞样细胞 沉淀培养，并分泌富含硫酸化蛋白聚糖的基质，其中含有 I1 型胶原蛋白。软骨形成的诱导可通过以下因素得到增强： 作为转化生长因子（TGF）-Bi或骨形态发生蛋白-2（BMP-2）， 先前已被证明可以促进胚胎中的软骨形成 间充质细胞。我们认为这些成骨细胞可能代表 以前未被识别的多能间充质祖细胞群体 细胞。具体目标是： 1 ) 鉴定和分离软骨祖细胞 来自成人小梁骨的细胞； 2）表征差异化 骨源性软骨祖细胞程序； 3) 确定 骨源性软骨祖细胞的软骨形成活性的可塑性 细胞。完成这些研究应明确其特征和 新型软骨祖细胞群分化的调节。 这项研究还将确定这些成人小梁骨衍生细胞是否 可作为软骨工程和修复的祖细胞来源。