Zhou Ying, Yu Dan, Zhu Huiyong
Department of Oral and Maxillofacial Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China.
In Vitro Cell Dev Biol Anim. 2014 Oct;50(9):822-30. doi: 10.1007/s11626-014-9778-6. Epub 2014 Jun 17.
Human bone marrow stromal cells (hBMSCs) possess multilineage differentiation potential and play an important role in modern tissue engineering. However, the development of culture media to maintain hBMSCs in an undifferentiated, self-renewing state during their robust proliferation remains a challenge. We developed and tested modified growth medium [medium 1: epidermal growth factor (EGF), platelet-derived growth factor (PDGF), low glucose, 2% fetal calf serum (FCS)] on hBMSCs by comparing primary cell isolation, multipassage expansion, culture morphology, proliferation, and cellular phenotype, and performing an expression analysis of intrinsic-regulated genes to other two media. Cell morphology, proliferation, and phenotype varied among the media, while cells cultured in medium 1 displayed small, spindle-shaped morphology with the highest rate of growth capacities and the expected phenotype. RT-PCR analysis showed that medium 1 displayed the lowest expression levels of osteogenic genes, chondrogenic genes (osteonectin, runt-related transcription factor 2, cartilage oligo matrix protein, and SOX9), and adipogenic genes (lipoprotein lipase). The expression of another adipogenic gene, peroxisome proliferator-activator receptor-γ2, was higher in medium 1 but did not reach significance. In addition, hBMSCs expanded in medium 1 showed the highest expression ratio of self-renewing-related genes Krüppel-like factor 2 (KLF2) and KLF5. In conclusion, medium 1 allows for better expansion and pluripotency maintenance of hBMSCs and serves as a preferred alternative to traditional serum-containing media for research applications and future clinical use.
人骨髓基质细胞(hBMSCs)具有多向分化潜能,在现代组织工程中发挥着重要作用。然而,开发在hBMSCs旺盛增殖过程中使其保持未分化、自我更新状态的培养基仍然是一项挑战。我们通过比较原代细胞分离、多次传代扩增、培养形态、增殖和细胞表型,并对其他两种培养基进行内在调控基因表达分析,开发并测试了改良生长培养基[培养基1:表皮生长因子(EGF)、血小板衍生生长因子(PDGF)、低糖、2%胎牛血清(FCS)]对hBMSCs的影响。不同培养基中的细胞形态、增殖和表型各不相同,而在培养基1中培养的细胞呈现小的纺锤形形态,具有最高的生长能力和预期的表型。逆转录聚合酶链反应(RT-PCR)分析表明,培养基1中骨生成基因、软骨生成基因(骨连接蛋白、 runt相关转录因子2、软骨寡聚基质蛋白和SOX9)和成脂基因(脂蛋白脂肪酶)的表达水平最低。另一个成脂基因过氧化物酶体增殖物激活受体γ2在培养基1中的表达较高,但未达到显著水平。此外,在培养基1中扩增的hBMSCs显示出自我更新相关基因Krüppel样因子2(KLF2)和KLF5的最高表达率。总之,培养基1能更好地扩增和维持hBMSCs的多能性,是研究应用和未来临床使用中传统含血清培养基的首选替代品。