Do-Hun Kim1,2,3, Hyun-Ju Cho3, Chul-Yong Park1,3, Myung Soo Cho4, Dong-Wook Kim5,6,7. 1. Department of Physiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. 2. Brain Korea 21 PLUS Program for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. 3. S.Biomedics Co., Ltd, 2nd Floor, 28 Seongsui-ro 26-gil, Seongdong-gu, Seoul, 04797, South Korea. 4. S.Biomedics Co., Ltd, 2nd Floor, 28 Seongsui-ro 26-gil, Seongdong-gu, Seoul, 04797, South Korea. tpguy@sbiomedics.com. 5. Department of Physiology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. dwkim2@yuhs.ac. 6. Brain Korea 21 PLUS Program for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, South Korea. dwkim2@yuhs.ac. 7. S.Biomedics Co., Ltd, 2nd Floor, 28 Seongsui-ro 26-gil, Seongdong-gu, Seoul, 04797, South Korea. dwkim2@yuhs.ac.
Abstract
BACKGROUND: Spinal cord injury (SCI) results in permanent impairment of motor and sensory functions at and below the lesion site. There is no therapeutic option to the functional recovery of SCI involving diverse injury responses of different cell types in the lesion that limit endogenous nerve regeneration. In this regard, cell replacement therapy utilizing stem cells or their derivatives has become a highly promising approach to promote locomotor recovery. For this reason, the demand for a safe and efficient multipotent cell source that can differentiate into various neural cells is increasing. In this study, we evaluated the efficacy and safety of human polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (hNPCsPSA-NCAM+) as a treatment for SCI. METHODS: One hundred thousand hNPCsPSA-NCAM+ isolated from human embryonic stem cell-derived NPCs were transplanted into the lesion site by microinjection 7 days after contusive SCI at the thoracic level. We examined the histological characteristics of the graft and behavioral improvement in the SCI rats 10 weeks after transplantation. RESULTS: Locomotor activity improvement was estimated by the Basso-Beattie-Bresnahan locomotor rating scale. Behavioral tests revealed that the transplantation of the hNPCsPSA-NCAM+ into the injured spinal cords of rats significantly improved locomotor function. Histological examination showed that hNPCsPSA-NCAM+ had differentiated into neural cells and successfully integrated into the host tissue with no evidence of tumor formation. We investigated cytokine expressions, which led to the early therapeutic effect of hNPCsPSA-NCAM+, and found that some undifferentiated NPCs still expressed midkine, a well-known neurotrophic factor involved in neural development and inflammatory responses, 10 weeks after transplantation. CONCLUSION: Our results demonstrate that hNPCsPSA-NCAM+ serve as a safe and efficient cell source which has the potential to improve impaired motor function following SCI.
BACKGROUND: Spinal cord injury (SCI) results in permanent impairment of motor and sensory functions at and below the lesion site. There is no therapeutic option to the functional recovery of SCI involving diverse injury responses of different cell types in the lesion that limit endogenous nerve regeneration. In this regard, cell replacement therapy utilizing stem cells or their derivatives has become a highly promising approach to promote locomotor recovery. For this reason, the demand for a safe and efficient multipotent cell source that can differentiate into various neural cells is increasing. In this study, we evaluated the efficacy and safety of human polysialylated-neural cell adhesion molecule (PSA-NCAM)-positive neural precursor cells (hNPCsPSA-NCAM+) as a treatment for SCI. METHODS: One hundred thousand hNPCsPSA-NCAM+ isolated from human embryonic stem cell-derived NPCs were transplanted into the lesion site by microinjection 7 days after contusive SCI at the thoracic level. We examined the histological characteristics of the graft and behavioral improvement in the SCI rats 10 weeks after transplantation. RESULTS: Locomotor activity improvement was estimated by the Basso-Beattie-Bresnahan locomotor rating scale. Behavioral tests revealed that the transplantation of the hNPCsPSA-NCAM+ into the injured spinal cords of rats significantly improved locomotor function. Histological examination showed that hNPCsPSA-NCAM+ had differentiated into neural cells and successfully integrated into the host tissue with no evidence of tumor formation. We investigated cytokine expressions, which led to the early therapeutic effect of hNPCsPSA-NCAM+, and found that some undifferentiated NPCs still expressed midkine, a well-known neurotrophic factor involved in neural development and inflammatory responses, 10 weeks after transplantation. CONCLUSION: Our results demonstrate that hNPCsPSA-NCAM+ serve as a safe and efficient cell source which has the potential to improve impaired motor function following SCI.
Authors: Mark Noble; Margot Mayer-Pröschel; Jeannette E Davies; Stephen J A Davies; Christoph Pröschel Journal: Curr Opin Neurol Date: 2011-12 Impact factor: 5.710
Authors: Wolfram Tetzlaff; Elena B Okon; Soheila Karimi-Abdolrezaee; Caitlin E Hill; Joseph S Sparling; Jason R Plemel; Ward T Plunet; Eve C Tsai; Darryl Baptiste; Laura J Smithson; Michael D Kawaja; Michael G Fehlings; Brian K Kwon Journal: J Neurotrauma Date: 2010-04-20 Impact factor: 5.269
Authors: Hans S Keirstead; Gabriel Nistor; Giovanna Bernal; Minodora Totoiu; Frank Cloutier; Kelly Sharp; Oswald Steward Journal: J Neurosci Date: 2005-05-11 Impact factor: 6.167
Authors: Victoria Moreno-Manzano; Francisco Javier Rodríguez-Jiménez; Mireia García-Roselló; Sergio Laínez; Slaven Erceg; Maria Teresa Calvo; Mohammad Ronaghi; Maria Lloret; Rosa Planells-Cases; Jose María Sánchez-Puelles; Miodrag Stojkovic Journal: Stem Cells Date: 2009-03 Impact factor: 6.277