Isobe Ken-ichi, Cheng Zhao, Nishio Naomi, Suganya Thanasegan, Tanaka Yuriko, Ito Sachiko
Department of Immunology, Nagoya University Graduate School of Medicine, 65 Turumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan
N Biotechnol. 2015 Jan 25;32(1):169-79. doi: 10.1016/j.nbt.2014.11.002.
Human histocompatibility antigens are quite heterogeneous and promote the rejection of transplanted tissue. Recent advances in stem cell research that enable the use of a patient's own stem cells for transplantation are very important because rejection could be avoided. In particular, Yamanaka’s group in Japan gave new hope to patients with incurable diseases when they developed induced murine pluripotent stem cells (iPSCs) in 2006 and human iPSCs in 2007. Whereas embryonic stem cells (ESCs) are derived from the inner cell mass and are supported in culture by LIF, iPSCs are derived from fetal or adult somatic cells. Through the application of iPSC technology, adult somatic cells can develop a pluripotent state. One advantage of using iPSCs instead of ESCs in regenerative medicine is that (theoretically) immune rejection could be avoided, although there is some debate about immune rejection of a patient's own iPSCs. Many diseases occur in elderly patients. In order to use regenerative medicine with the elderly, it is important to demonstrate that iPSCs can indeed be generated from older patients. Recent findings have shown that iPSCs can be established from aged mice and aged humans. These iPSCs can differentiate to cells from all three germ layers. However, it is not known whether iPSCs from aged mice or humans show early senescence. Before clinical use of iPSCs, issues related to copy number variation, tumorigenicity and immunogenicity must be resolved. It is particularly important that researchers have succeeded in generating iPSCs that have differentiated to somatic cells related to specific diseases of the elderly, including atherosclerosis, diabetes, Alzheimer's disease and Parkinson's disease. These efforts will facilitate the use of personalized stem cell transplantation therapy for currently incurable diseases.
人类组织相容性抗原具有高度异质性，会促进移植组织的排斥反应。干细胞研究的最新进展使得利用患者自身的干细胞进行移植成为可能，这一点非常重要，因为可以避免排斥反应。特别是，日本山中伸弥团队在2006年培育出诱导性小鼠多能干细胞（iPSC），并于2007年培育出人类iPSC，这给患有不治之症的患者带来了新希望。胚胎干细胞（ESC）源自内细胞团，在培养过程中由白血病抑制因子（LIF）支持，而iPSC则源自胎儿或成人体细胞。通过应用iPSC技术，成人体细胞可以发展为多能状态。在再生医学中使用iPSC而非ESC的一个优势是（理论上）可以避免免疫排斥，尽管对于患者自身iPSC的免疫排斥存在一些争议。许多疾病发生在老年患者身上。为了在老年人中应用再生医学，证明确实可以从老年患者中生成iPSC非常重要。最近的研究结果表明，可以从老年小鼠和老年人中建立iPSC。这些iPSC可以分化为来自所有三个胚层的细胞。然而，尚不清楚来自老年小鼠或人类的iPSC是否会表现出早期衰老。在iPSC临床应用之前，必须解决与拷贝数变异、致瘤性和免疫原性相关的问题。特别重要的是，研究人员已经成功培育出分化为与老年人特定疾病相关的体细胞的iPSC，这些疾病包括动脉粥样硬化、糖尿病、阿尔茨海默病和帕金森病。这些努力将有助于将个性化干细胞移植疗法应用于目前无法治愈的疾病。
