Human iPS cell derived neural cell sheets exhibit mature neural and extendable scaffold functions and promote recovery in injured mouse spinal cords

We developed neural cell sheets being positive for mature motoneuron markers, such as βIII tubulin, islet1 and HB9, from human induced pluripotent stem (hiPS) cells after embryoid body formation. We transplanted the neural cell sheets into the complete transection sites of spinal cord injury (SCI) model mice. We assessed functional and histological analyses of the SCI mice and compared the data with those of hiPS cell derived neural stem/progenitor (NSP) cell transplanted SCI mice. Neurofilament medium (NFM), βIII tubulin, and HB9 positive cells were significantly increased in vitro in neural cell sheets compared with those in NSP cells. The neural cell sheets expressed remarkably high mRNA of NFM and islet 1 compared with NSP cells. After transplantation, the neural cell sheets elongated human neural cell adhesion molecule (hNCAM) positive axons over the L1 spinal level and carried a neuron tracer cholera toxin β subunit (CTβ) to downstream region. The sheet transplantation showed significantly better locomotor recovery of SCI mice until day 65 than NSP cell transplantation. The sheet transplantation tended to improve spinal cord atrophy in caudal part of injured/grafted site to the same extent as NSP cell transplantation. We suggest that the neural cell sheets derived from hiPS cells may be one of the most effective treatment for SCI, through the mature neural and extendable scaffold functions. Correspondence to: Noboru Suzuki MD, Ph.D, Department of Immunology and Medicine, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamaeku, Kawasaki, Kanagawa 216-8511, Japan, Tel: +81-44-977-8111 (ex 3547), Fax: +81-44-976-3315, E-mail: [email protected]