Ghasemi-Dehkordi Payam, Allahbakhshian-Farsani Mehdi, Abdian Narges, Mirzaeian Amin, Saffari-Chaleshtori Javad, Heybati Fatemeh, Mardani Gashtasb, Karimi-Taghanaki Alireza, Doosti Abbas, Jami Mohammad-Saeid, Abolhasani Marziyeh, Hashemzadeh-Chaleshtori Morteza
Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Rahmatieh, 8813833435, Shahrekord, Iran.
Department of Hematology and Blood Banking, Faculty of Allied Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
J Cell Commun Signal. 2015 Sep;9(3):233-46. doi: 10.1007/s12079-015-0289-3. Epub 2015 Mar 29.
Human induced pluripotent stem cells (hiPSCs) are a type of pluripotent stem cells artificially derived from an adult somatic cell (typically human fibroblast) by forced expression of specific genes. In recent years, different feeders like inactivated mouse embryonic fibroblasts (MEFs), human dermal fibroblasts (HDFs), and feeder free system have commonly been used for supporting the culture of stem cells in undifferentiated state. In the present work, the culture of hiPSCs and their characterizations on BD Matrigel (feeder-and serum-free system), MEF and HDF feeders using cell culture methods and molecular techniques were evaluated and compared. The isolated HDFs from foreskin samples were reprogrammed to hiPSCs using gene delivery system. Then, the pluripotency ability of hiPSCs cultured on each layer was determined by teratoma formation and immunohistochemical staining. After EBs generation the expression level of three germ layers genes were evaluated by Q-real-time PCR. Also, the cytogenetic stability of hiPSCs cultured on each condition was analyzed by karyotyping and comet assay. Then, the presence of pluripotency antigens were confirmed by Immunocytochemistry (ICC) test and alkaline phosphatase staining. This study were showed culturing of hiPSCs on BD Matrigel, MEF and HDF feeders had normal morphology and could maintain in undifferentiated state for prolonged expansion. The hiPSCs cultured in each system had normal karyotype without any chromosomal abnormalities and the DNA lesions were not observed by comet assay. Moreover, up-regulation in three germ layers genes in cultured hiPSCs on each layer (same to ESCs) compare to normal HDFs were observed (p < 0.05). The findings of the present work were showed in stem cells culturing especially hiPSCs both MEF and HDF feeders as well as feeder free system like Matrigel are proper despite benefits and disadvantages. Although, MEFs is suitable for supporting of stem cell culturing but it can animal pathogens transferring and inducing immune response. Furthermore, HDFs have homologous source with hiPSCs and can be used as feeder instead of MEF but in therapeutic approaches the cells contamination is a problem. So, this study were suggested feeder free culturing of hiPSCs on Matrigel in supplemented media (without using MEF conditioned medium) resolves these problems and could prepare easy applications of hiPSCs in therapeutic approaches of regenerative medicine such as stem-cell therapy and somatic cell nuclear in further researches.
人诱导多能干细胞(hiPSCs)是一类通过强制表达特定基因从成体细胞(通常是人类成纤维细胞)人工衍生而来的多能干细胞。近年来,不同的饲养层,如灭活的小鼠胚胎成纤维细胞(MEFs)、人真皮成纤维细胞(HDFs)以及无饲养层系统,常用于支持干细胞在未分化状态下的培养。在本研究中,我们使用细胞培养方法和分子技术,对hiPSCs在BD基质胶(无饲养层和无血清系统)、MEF和HDF饲养层上的培养及其特性进行了评估和比较。从包皮样本中分离出的HDFs使用基因递送系统重编程为hiPSCs。然后,通过畸胎瘤形成和免疫组织化学染色来确定在各层上培养的hiPSCs的多能性能力。在生成胚状体(EBs)后,通过Q-实时PCR评估三个胚层基因的表达水平。此外,通过核型分析和彗星试验分析在每种条件下培养的hiPSCs的细胞遗传学稳定性。然后,通过免疫细胞化学(ICC)试验和碱性磷酸酶染色确认多能性抗原的存在。本研究表明,hiPSCs在BD基质胶、MEF和HDF饲养层上培养具有正常形态,并且可以在未分化状态下长期扩增。在每个系统中培养的hiPSCs具有正常核型,没有任何染色体异常,并且彗星试验未观察到DNA损伤。此外,与正常HDFs相比,在各层上培养的hiPSCs中三个胚层基因上调(与胚胎干细胞相同)(p < 0.05)。本研究结果表明,在干细胞培养中,特别是hiPSCs培养,MEF和HDF饲养层以及像基质胶这样的无饲养层系统尽管各有优缺点,但都是合适的。虽然,MEFs适合支持干细胞培养,但它可能会传播动物病原体并引发免疫反应。此外,HDFs与hiPSCs有同源来源,可以用作MEF的替代饲养层,但在治疗方法中细胞污染是一个问题。因此,本研究建议在补充培养基中(不使用MEF条件培养基)在基质胶上对hiPSCs进行无饲养层培养可以解决这些问题,并能在再生医学的治疗方法如干细胞治疗和体细胞克隆的进一步研究中为hiPSCs的应用提供便利。