臨床婦人科産科71巻5号

2017年05月発行

今月の臨床 万能幹細胞・幹細胞とゲノム編集─再生医療の進歩が医療を変える

ES細胞・iPS細胞の臨床応用

脊髄損傷の治療

著者： 大久保寿樹¹² 中村雅也¹ 岡野栄之²

所属機関： ¹慶應義塾大学医学部整形外科学教室 ²慶應義塾大学医学部生理学教室

ページ範囲：P.407 - P.415

文献概要

●これまで再生不可能といわれてきた脊髄損傷に対し，各病期において，さまざまな角度からアプローチがなされ，その効果が得られつつある．

●ヒトiPS細胞を用いた脊髄損傷に対する神経幹/前駆細胞移植においては，今後ヒトへの臨床応用に向け，その有効性だけでなく安全性の検討も必要である．

●ヒトiPS細胞から樹立した神経幹/前駆細胞をNotchシグナル阻害薬で前処理することで，移植細胞の腫瘍化を予防し，安全に運動機能を回復・維持させることに成功した．

参考文献

1）Ramón y Cajal S : Degeneration and regeneration of the nervous system（Translated by RM Day from the 1913 Spanish edition）. Oxford University Press, Oxford, 1928

2）McDonald JW, et al : Transplanted embryonic stem cells survive, differentiated and promote recovery in injured rat spinal cord. Nat Med 5 : 1410─1412, 1999

3）Kitamura K, et al : Human hepatocyte growth factor promotes functional recovery in primates after spinal cord injury. PLoS One 6 : e27706, 2011

4）Kaneko S, et al : A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord. Nat Med 12 : 1380─1389, 2006

5）Mothe, et al : Advances in stem cell therapy for spinal cord injury. J Clin Invest 122 : 3824─3834, 2012

6）Fawcett JW, et al : Guidelines for the conduct of clinical trials for spinal cord injury as developed by the ICCP panel : spontaneous recovery after spinal cord injury and statistical power needed for therapeutic clinical trials. Spinal Cord 45 : 190─205, 2007

7）Steeves J, et al : Report of internationall clinical trials workshop on spinal cord injury February 20-21, 2004, Vancouver, Canada. Spinal Cord 42 : 591─597, 2004

8）Okano H, et al : Stem cell biology of the central nervous system. J Neurosci Res 69 : 698─707, 2002

9）Okada Y, et al : Spatio-temporal recapitulation of central nerve system development by murine ES cell-derived neural/stem progenitor cells. Stem Cells 26 : 3086─3098, 2008

10）Okita K, et al : Generation of gremlin-competent induced pluripotent stem cells. Nature 448 : 313─317, 2007

11）Kumagai G, et al : Roles of ES cell-derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury. PLoS One 11 : e7706, 2009

12）Takahashi K, et al : Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126 : 663─676, 2006

13）Takahashi K, et al : Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131 : 861─872, 2007

14）Okano H, et al : Steps toward safe cell therapy using induced pluripotent stem cells. Circ Res 112 : 523─533, 2013

15）Tuji O, et al : Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proc Natl Acad Sci USA 107 : 12704─12709, 2010

16）Nori S, et al : Grafted human-induced pluripotent stem-cell-derived neurospheres promote motor functional recovery after spinal cord injury in mice. Proc Natl Acad Sci USA 108 : 16825─16830, 2011

17）Kobayashi Y, et al : Pre-evaluated safe human iPSC-derived neural stem cells promote functional recovery after spinal cord injury in common marmoset without tumorigenicity. PLoS One 12 : e52787, 2012

18）Nori S, et al : Long-term safety issues of iPSC-based cell therapy in a spinal cord injury model : oncogenic transformation with epithetial-mesenchymal transition. Stem Cell Reports 4 : 360─373, 2015

19）Okubo T, et al : Pretreatment with a γ-secretase inhibitor prevents tumor-like overgrowth in human iPSC-derived transplants for spinal cord injury. Stem Cell Reports 7 : 1─15, 2016