Farrington-Rock C, Crofts N J, Doherty M J, Ashton B A, Griffin-Jones C, Canfield A E
Wellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester M13 9PT, UK.
Circulation. 2004 Oct 12;110(15):2226-32. doi: 10.1161/01.CIR.0000144457.55518.E5. Epub 2004 Oct 4.
Previous studies have shown that pericytes can differentiate into osteoblasts and form bone. This study investigated whether pericytes can also differentiate into chondrocytes and adipocytes.
Reverse transcription-polymerase chain reaction demonstrated that pericytes express mRNA for the chondrocyte markers Sox9, aggrecan, and type II collagen. Furthermore, when cultured at high density in the presence of a defined chondrogenic medium, pericytes formed well-defined pellets comprising cells embedded in an extracellular matrix rich in sulfated proteoglycans and type II collagen. In contrast, when endothelial cells were cultured under the same conditions, the pellets disintegrated after 48 hours. In the presence of adipogenic medium, pericytes but not endothelial cells expressed mRNA for peroxisome proliferator-activated receptor-gamma2 (an adipocyte-specific transcription factor) and incorporated lipid droplets that stained with oil red O. To confirm that pericytes can differentiate along the chondrocytic and adipocytic lineages in vivo, these cells were inoculated into diffusion chambers and implanted into athymic mice for 56 days. Accordingly, mineralized cartilage, fibrocartilage, and a nonmineralized cartilaginous matrix with lacunae containing chondrocytes were observed within these chambers. Small clusters of cells that morphologically resembled adipocytes were also identified.
These data demonstrate that pericytes are multipotent cells that may contribute to growth, wound healing, repair, and/or the development and progression of various pathological states.
先前的研究表明,周细胞可分化为成骨细胞并形成骨组织。本研究调查周细胞是否也能分化为软骨细胞和脂肪细胞。
逆转录 - 聚合酶链反应表明,周细胞表达软骨细胞标志物Sox9、聚集蛋白聚糖和II型胶原蛋白的mRNA。此外,当在特定的软骨形成培养基中高密度培养时,周细胞形成了明确的细胞团,这些细胞团包含嵌入富含硫酸化蛋白聚糖和II型胶原蛋白的细胞外基质中的细胞。相比之下,当内皮细胞在相同条件下培养时,细胞团在48小时后解体。在脂肪形成培养基存在的情况下,周细胞而非内皮细胞表达过氧化物酶体增殖物激活受体γ2(一种脂肪细胞特异性转录因子)的mRNA,并摄取了用油红O染色的脂滴。为了证实周细胞在体内能够沿着软骨细胞和脂肪细胞谱系分化,将这些细胞接种到扩散小室中并植入无胸腺小鼠体内56天。因此,在这些小室内观察到了矿化软骨、纤维软骨以及含有软骨细胞的具有腔隙的非矿化软骨基质。还鉴定出了形态上类似于脂肪细胞的小细胞簇。
这些数据表明,周细胞是多能细胞,可能有助于生长、伤口愈合、修复和/或各种病理状态的发展和进展。