日本庆应义塾大学和京都大学研究人员在新一期美国《国家科学院学报》上发表报告说，他们先调查iPS细胞发育成癌细胞的风险，发现了一种安全性很高的iPS细胞。随后他们利用这种iPS细胞进行治疗，成功恢复了脊髓受损老鼠的行动能力。

为了调查利用老鼠各种体细胞制造出的iPS细胞发育成癌细胞的风险，研究人员将这些细胞移植到经过特殊培养的老鼠脑部。结果发现，利用老鼠胎儿皮肤细胞制造的iPS细胞在移植半年后也没有发育成癌细胞，从而判断这种iPS细胞是最安全的。

接下来，研究人员将这种iPS细胞培育成神经干细胞，然后移植到因脊髓神经受损而失去行动能力的老鼠体内，结果新细胞在老鼠脊髓内成活，并且使与运动机能相关的神经组织获得再生，老鼠行动能力因此得到恢复。

研究人员说，利用人体细胞中纤维原细胞制作的iPS细胞，被认为具有高癌化危险，因此iPS细胞的再生医疗前景很不明朗。而利用此次方法进行人体组织再生治疗，治疗安全性将得到大大提高。

原文出处：

PNAS doi: 10.1073/pnas.0910106107

Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury
Osahiko Tsujia,b,1, Kyoko Miuraa,c,1, Yohei Okadaa,d, Kanehiro Fujiyoshia,b, Masahiko Mukainoa,e, Narihito Nagoshia,b,f, Kazuya Kitamuraa,b, Gentaro Kumagaia,g, Makoto Nishinoa, Shuta Tomisatoa, Hisanobu Higashia, Toshihiro Nagaih, Hiroyuki Katoha,b,f, Kazuhisa Kohdaa, Yumi Matsuzakia, Michisuke Yuzakia, Eiji Ikedai,j, Yoshiaki Toyamab, Masaya Nakamurab,2, Shinya Yamanakac, and Hideyuki Okanoa,2

Departments of aPhysiology and
bOrthopedic Surgery, School of Medicine, Keio University, Shinjuku, Tokyo 160-8582, Japan;
cCenter for Induced Pluripotent Stem Cell Research and Application, Kyoto University, Kyoto 606-8507, Japan;
dKanrinmaru-Project and
Departments of eRehabilitation Medicine,
hElectron Microscope Laboratory, and
iPathology, School of Medicine, Keio University, Tokyo 160-8582, Japan;
fDepartment of Orthopedic Surgery, National Hospital Organization, Murayama Medical Center, Tokyo 208-0011, Japan;
gDepartment of Orthopedic Surgery, Graduate School of Medicine, Hirosaki University, Aomori 036-8560, Japan; and
jDepartment of Pathology, Graduate School of Medicine, Yamaguchi University, Yamaguchi 755-8505, Japan

Various types of induced pluripotent stem (iPS) cells have been established by different methods, and each type exhibits different biological properties. Before iPS cell-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Here we show the directed neural differentiation of murine iPS cells and examine their therapeutic potential in a mouse spinal cord injury (SCI) model. “Safe” iPS-derived neurospheres, which had been pre-evaluated as nontumorigenic by their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse brain, produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes in vitro. Furthermore, when the safe iPS-derived neurospheres were transplanted into the spinal cord 9 d after contusive injury, they differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in remyelination and induced the axonal regrowth of host 5HT+ serotonergic fibers, promoting locomotor function recovery. However, the transplantation of iPS-derived neurospheres pre-evaluated as “unsafe” showed robust teratoma formation and sudden locomotor functional loss after functional recovery in the SCI model. These findings suggest that pre-evaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI.