Research Highlights

Vol.1, August 2014

Safer cells progress spinal treatment research A stem cell treatment is developed that helps spinal injury recovery without use of ethically controversial fetal cells.

Recent research demonstrated improved spinal injury recovery in rodents and non-human primates injected with stem cells. However, these cells are derived from fetuses raising ethical issues that have stalled further progress with clinical trials involving humans. Hideyuki Okano, from Keio University, and colleagues in Japan have since developed another type of stem cell that can also provide effective treatments for spinal injuries.

The approach uses neural cells derived from clones where the ability to differentiate into a number of different cell types is induced - ‘induced pluripotent stem cells’ (iPSCs). The safety of these cells has already been evaluated. The neural stem/progenitor cells derived from iPSCs were injected into marmosets nine days after a spinal injury inflicted just below the skull. Another group of marmosets were injected with phosphate buffered saline solution nine days after injury as controls.

The marmosets were monitored in terms of mobility and hand grip strength. Following paralysis immediately after the injury, the animals began to recover mobility, but animals from the control group remained limited to around 60-70% of the recovery of marmosets injected with iPSCs-derived neural stem/progenitor cells. Magnetic resonance imaging (MRI) also revealed the control group had greater damage to the myelin sheath that facilitates the neuronal functions through the insulation of neuronal axons.
Twelve weeks after the injury the animals were killed and the spinal cord tissue analysed further. The injected cells were shown to differentiate into three different types of neural cell with no tumors forming, a common concern for human iPSC-based treatments.

The authors’ report on the work concludes that these human iPSCs-based cell therapy hold great promise as a cell source for the study and treatment of human diseases and disorders. However they add, “It is critical to carefully assess safety concerns prior to their use in the clinic.”

Publication and Affiliation

Yoshiomi Kobayashi^1,2†, Yohei Okada^1†, Go Itakura^1,2, Hiroki Iwai^1,2, Soraya Nishimura^1,2,
Akimasa Yasuda¹, Satoshi Nori¹, Keigo Hikishima^2,3, Tsunehiko Konomi^1,2, Kanehiro Fujiyoshi⁴,
Osahiko Tsuji⁵, Yoshiaki Toyama¹, Shinya Yamanaka⁶, Masaya Nakamura^1*, Hideyuki Okano^2* Pre-Evaluated Safe Human iPSC-Derived Neural Stem Cells Promote Functional Recovery after Spinal Cord Injury in Common Marmoset without Tumorigenicity. PLoS ONE, 7 e52787, (2012).

Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
Department of Physiology, School of Medicine, Keio University, Tokyo, Japan
Central Institute for Experimental Animals, Kanagawa, Japan
Department of Orthopedic Surgery, National Hospital Organization Murayama Medical Center, Tokyo, Japan
Department of Orthopedic Surgery, Saitama Social Insurance Hospital, Saitama, Japan
Center for iPS Cell Research and Application (CiRA), Kyoto, Japan

* E-mail: masa@a8.keio.jp; hidokano@a2.keio.jp
† These authors contributed equally to this work.

Figure:

Caption: Representative fluorescence images of axial sections through the epicenter of the injury at 12 weeks post-engraftment. The region enclosed by the dashed line indicates the demylinated area - grafted human iPSC-neural stem/progenitor cells prevent demyelination after the spinal cord injury. © 2012 PLOS ONE