摘要
目的观察细胞因子和生长因子在人脐带Wharton胶间质干细胞(WMSCs)的表达,了解其生物学特性,为其临床应用提供实验依据。方法取人足月妊娠新生儿脐带,分离MSCs,应用成纤维细胞集落形成实验验证其干细胞特性,流式细胞术鉴定其表面分了特性,蛋白芯片方法观察细胞因子和生长因子的表达。结果所检测的79种因子除白介素(IL)-13表达痕量外,其他均表达于WMSCs,表达从多到少(OD值〉0.800)依次为IL-8、生长相关癌基因(GRO)、IL-6、IL-1β、IL-1α和GRO—α;它表达6种免疫抑制功能的因子和肿瘤生长抑制因子,这对减少MSCs用于异体移植时的免疫排斥及瘤变的可能性起一定作用,而其表达的金属蛋白酶抑制因子TIMP-1、TIMP-2将对其应用于作内移植时起到保护自身的作用;多种神经生长因子(脑源性神经生长因子、神经生长素-3、神经生长素-4、胶质细胞源性神经生长因子)的表达表明WMSCs易于血神经细胞诱导分化。结论 人脐带WMSCs踢十扶得,表达的细胞因子有利于其应用于异体移植,减少免疫排斥及恶变,并保护其自身在体内分化生长.是一个很有前景的新型种子细胞,可应用于再生医学及构建组织工程组织或器官。
Objective To characterize Wharton's jelly-derived mesenchymal stem cells from human umbilical cord (WMSCs) by observing their cytokine and growth factor expressions. Methods We isolated WMSCs from tire mubilical cords fl'om heahhy full-term newborns. We verified the sternness by colony-forming unit-fihrohlast (CFU-F) assay, detected the cell surface marker expression by flow cytometry, and observed the cytokine and growth factor expressions by protein chip assay. Results Human WMSCs were found to synthesize substantial levels of 78 of the 79 factors on the chip, with the only exception of IL-13. WMSCs were shown to produce significantly high levels [mean optical density (OD) 〉 0. 800] of the pro-inflammatory eytokines IL-1α, IL-1β, IL-6 and IL-8, as well as the chemokines growth related oncogene (GRO) and GRO-α. The expressed growth factors verified the osteogenesis and chondrogenesis differentiation potentials of WMSCs. In addition, the expression profile included 6 immune suppressive-related factors and tumor growth suppressors, which may reduce the chance of immune rejection and tumorigenesis of the allograft cells. Expressions of metalloproteases inhibitor, TIMP-1 and TIMP-2, couht be important for the generation of functional tissue as they may prevent the breakdown of newly synthesized extracelhdar cell matrix (ECM) and protect the perivascular niche. Expressions of nerve growth factors (BDNF, NT-3, NT-4 and GDNF) indicate WMSCs have a potential to be induced and differentiated into nerve cells. Conclusions WMSCs are easy to obtain. The cytnkines they express can reduce the chance of immune rejection and tumorigenesis and protect the implanted cells from metalloproteases digestion. So WMSCs may be a promising cellular candidate for use in regenerative medicine and fabrication of engineering tissue or organ.
出处
《中华创伤骨科杂志》
CAS
CSCD
北大核心
2013年第12期1071-1075,共5页
Chinese Journal of Orthopaedic Trauma
基金
国家高技术研究发展计划(863计划)(2012AA020502)
国家自然科学基金(81000810,81071458)
国家重点基础研究发展计划(973计划)(2012CB518106)
国家科技支撑计划(2009BA187802)
全军十二五重点计划(BWS11J025)
关键词
脐带
间充质干细胞
细胞因子类
细胞因子抗体芯片
Umbilical cord
Mesenehymal stem cells
Cytokine
Cytokine antibody micro-array