日本科学家发现造成口臭(halitosis)的气味难闻的化合物非常适合用于收集从人牙髓(dental pulp)中提取的干细胞。2012年2月27日,这些研究结果发表在Journal of Breath Research期刊上。
在这项研究中,研究人员证实硫化氢(hydrogen sulphide, H2S)能够增加成体干细胞分化为肝细胞的能力,从而提高成体干细胞作为未来肝细胞治疗的一种可靠来源的名声。
这是第一次发现肝细胞能够产自人牙髓,而且更让人印象深刻的是,它们能够大量生产同时保持高纯度。
该研究论文通讯作者Ken Yaegaki博士说,“高纯度意味着干细胞分化产生的组成其他组织的‘错误细胞’比较少,而且干细胞本身也很少有残留。再者,这些事实提示着接受肝细胞移植的病人几乎不可能产生畸胎瘤(teratoma)或癌症,而当用骨髓干细胞进行移植时则往往会产生这种情况。”
干细胞的令人注目的转化能力已成为全世界研究小组关注的重要焦点,同时也让科学家期待利用它们治疗包括帕金森疾病和阿尔茨海默疾病(Alzheimer's disease)在内的很多疾病。
在这项研究中,Ken Yaegaki博士和来自日本齿科大学的同事们利用来自牙髓---牙齿的中央部分,由结缔组织和细胞组成---的干细胞进行研究,其中这些干细胞是从正在接受常规拔牙的牙科患者的牙齿中获得的。
一旦干细胞被制备得足够多,它们就被分成两个批次(测试组和对照组)并且测试组细胞在H2S培养箱中孵育。在3天、6天和9天之后,它们分别被收集下来进行分析以便观察这些细胞是否成功地转化为肝细胞。
为了测试这些干细胞在H2S影响下是否能够成功地分化为肝细胞,研究人员进行一系列测试来研究干细胞分化产生的细胞是否拥有肝细胞的典型特征。除了在显微镜下的物理观察之外,研究人员研究了它们储存糖原的能力,并记录了细胞中尿素含量。
Yaegaki博士继续说道,“直到现在,没有人发明出再生大量肝细胞用于人类移植的实验方法。相比于利用胎牛血清生产肝细胞的传统方法,我们的方法产率高,而且更为重要的是,它也更安全。”
硫化氢(H2S)有着特有的臭鸡蛋气味,能够在全身组织中产生。尽管它所起的确切功能仍不清楚,但是研究人员相信它在很多生理过程和疾病状态中发挥着关键性作用。(生物谷:towersimper编译)
doi:10.1088/1752-7155/6/1/017103
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Hydrogen sulfide increases hepatic differentiation in tooth-pulp stem cells
Nikolay Ishkitiev, Bogdan Calenic, Izumi Aoyama, Hisataka Ii, Ken Yaegaki and Toshio Imai
The toxicity of hydrogen sulfide (H2S), an oral malodorous compound, is well reported. We have recently established an experimental model of hepatic differentiation from human tooth-pulp stem cells (HTPC) using serum-free medium. The objective of the present study is to determine the effect of H2S on hepatic differentiation. The CD117 positive cell fraction was obtained from deciduous HTPC using magnetic cell sorting. After 3–4 passages, cells were grown in Dulbecco's modified Eagle's medium supplemented with insulin-transferrin-selenium-x (ITS-x), embryotrophic factor (ETF) and hepatocyte growth factor (HGF) for hepatic commitment (five days). For hepatic differentiation the cells were cultured in Iscove's modified Dulbecco's medium supplemented with ITS-x, ETF, oncostatin, HGF and dexamethasone for 15 days in air containing 5% CO2, with or without H2S at 0.05 ng ml−1. Cells were assayed for the expression of hepatic markers α-fetoprotein, albumin or carbamoyl phosphate synthetase, and urea concentrations and glycogen synthesis were also determined. The panel of hepatic markers was expressed more in the test groups exposed to H2S than in the control groups. Urea and glycogen production were also increased, especially glycogen which was approximately five times greater compared to the control (p < 0.01). We concluded that H2S at physiological concentrations increased the ability of HTPC to undergo hepatogenic differentiation.