title: Phase I-II Clinical Trial Assessing Safety and Efficacy of Umbilical Cord Blood Mononuclear Cell Transplant Therapy of Chronic Complete Spinal Cord Injury.
abstract: Umbilical cord blood-derived mononuclear cell (UCB-MNC) transplants improve recovery in animal spinal cord injury (SCI) models. We transplanted UCB-MNCs into 28 patients with chronic complete SCI in Hong Kong (HK) and Kunming (KM). Stemcyte Inc. donated UCB-MNCs isolated from human leukocyte antigen (HLA ≥4:6)-matched UCB units. In HK, four patients received four 4-μl injections (1.6 million cells) into dorsal entry zones above and below the injury site, and another four received 8-μl injections (3.2 million cells). The eight patients were an average of 13 years after C5-T10 SCI. Magnetic resonance diffusion tensor imaging of five patients showed white matter gaps at the injury site before treatment. Two patients had fiber bundles growing across the injury site by 12 months, and the rest had narrower white matter gaps. Motor, walking index of SCI (WISCI), and spinal cord independence measure (SCIM) scores did not change. In KM, five groups of four patients received four 4-μl (1.6 million cells), 8-μl (3.2 million cells), 16-μl injections (6.4 million cells), 6.4 million cells plus 30 mg/kg methylprednisolone (MP), or 6.4 million cells plus MP and a 6-week course of oral lithium carbonate (750 mg/day). KM patients averaged 7 years after C3-T11 SCI and received 3-6 months of intensive locomotor training. Before surgery, only two patients walked 10 m with assistance and did not need assistance for bladder or bowel management before surgery. The rest could not walk or do their bladder and bowel management without assistance. At about a year (41-87 weeks), WISCI and SCIM scores improved: 15/20 patients walked 10 m ( p = 0.001) and 12/20 did not need assistance for bladder management ( p = 0.001) or bowel management ( p = 0.002). Five patients converted from complete to incomplete (two sensory, three motor; p = 0.038) SCI. We conclude that UCB-MNC transplants and locomotor training improved WISCI and SCIM scores. We propose further clinical trials.
authors.affiliation: Kunming General Hospital of Chengdu Military Command, Yunnan, P.R. China.|Kunming Tongren Hospital, Yunnan, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Prince of Wales Hospital, Division of Neurosurgery, Department of Surgery, Chinese University of Hong Kong, Shatin, Hong Kong, SAR, P.R. China.
authors.forename: Waisang
authors.initials: W
authors.lastname: Poon
authors.affiliation: Kunming General Hospital of Chengdu Military Command, Yunnan, P.R. China.|Kunming Tongren Hospital, Yunnan, P.R. China.
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Queen Mary Hospital, University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Gilberto Ka-Kit
authors.initials: GK
authors.lastname: Leung
authors.affiliation: Queen Mary Hospital, University of Hong Kong, Hong Kong, SAR, P.R. China.
authors.forename: Yatwa
authors.initials: Y
authors.lastname: Wong
authors.affiliation: Kunming General Hospital of Chengdu Military Command, Yunnan, P.R. China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Prince of Wales Hospital, Division of Neurosurgery, Department of Surgery, Chinese University of Hong Kong, Shatin, Hong Kong, SAR, P.R. China.
authors.forename: Stephanie C P
authors.initials: SCP
authors.lastname: Ng
authors.affiliation: Prince of Wales Hospital, Division of Neurosurgery, Department of Surgery, Chinese University of Hong Kong, Shatin, Hong Kong, SAR, P.R. China.
authors.forename: Kam Sze
authors.initials: KS
authors.lastname: Tsang
authors.affiliation: Prince of Wales Hospital, Division of Neurosurgery, Department of Surgery, Chinese University of Hong Kong, Shatin, Hong Kong, SAR, P.R. China.
authors.forename: David T F
authors.initials: DTF
authors.lastname: Sun
authors.affiliation: Prince of Wales Hospital, Division of Neurosurgery, Department of Surgery, Chinese University of Hong Kong, Shatin, Hong Kong, SAR, P.R. China.
authors.forename: David K
authors.initials: DK
authors.lastname: Yeung
authors.affiliation: Kunming General Hospital of Chengdu Military Command, Yunnan, P.R. China.|Kunming Tongren Hospital, Yunnan, P.R. China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Shen
authors.affiliation: Kunming General Hospital of Chengdu Military Command, Yunnan, P.R. China.|Kunming Tongren Hospital, Yunnan, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Niu
authors.affiliation: Kunming General Hospital of Chengdu Military Command, Yunnan, P.R. China.|Kunming Tongren Hospital, Yunnan, P.R. China.
authors.forename: Zhexi
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Kunming General Hospital of Chengdu Military Command, Yunnan, P.R. China.|Kunming Tongren Hospital, Yunnan, P.R. China.
authors.forename: Pengju
authors.initials: P
authors.lastname: Tan
authors.affiliation: Kunming General Hospital of Chengdu Military Command, Yunnan, P.R. China.
authors.forename: Shaofeng
authors.initials: S
authors.lastname: Tang
authors.affiliation: Kunming General Hospital of Chengdu Military Command, Yunnan, P.R. China.|Kunming Tongren Hospital, Yunnan, P.R. China.
authors.forename: Hongkun
authors.initials: H
authors.lastname: Gao
authors.affiliation: Kunming General Hospital of Chengdu Military Command, Yunnan, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Cha
authors.affiliation: Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Science, The University of Hong Kong, SAR, P.R. China.|GHM Institute of CNS Regeneration, and Medical Key Laboratory of Brain Function and Diseases, Jinan University, Guangzhou, P.R. China.|China Spinal Cord Injury Network, Hong Kong Science Technology Park, Hong Kong, SAR, P.R. China.
authors.forename: Kwok-Fai
authors.initials: KF
authors.lastname: So
authors.affiliation: Vista Biological Laboratory, Carlsbad, CA, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Fleischaker
authors.affiliation: W. M. Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ, USA.
authors.forename: Dongming
authors.initials: D
authors.lastname: Sun
authors.affiliation: China Spinal Cord Injury Network, Hong Kong Science Technology Park, Hong Kong, SAR, P.R. China.
authors.forename: John
authors.initials: J
authors.lastname: Chen
authors.affiliation: China Spinal Cord Injury Network, Hong Kong Science Technology Park, Hong Kong, SAR, P.R. China.
authors.forename: Jan
authors.initials: J
authors.lastname: Lai
authors.affiliation: China Spinal Cord Injury Network, Hong Kong Science Technology Park, Hong Kong, SAR, P.R. China.
authors.forename: Wendy
authors.initials: W
authors.lastname: Cheng
authors.affiliation: China Spinal Cord Injury Network, Hong Kong Science Technology Park, Hong Kong, SAR, P.R. China.|W. M. Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ, USA.
authors.forename: Wise
authors.initials: W
authors.lastname: Young
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D016651:Lithium Carbonate / Q000627:therapeutic use; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D015990:Placebo Effect; D020127:Recovery of Function; D013116:Spinal Cord / Q000000981:diagnostic imaging; D013119:Spinal Cord Injuries / Q000473:pathology / Q000628:therapy*; D016138:Walking; D055815:Young Adult
chemical_list: D016651:Lithium Carbonate; D008775:Methylprednisolone
keywords: Central pattern generator; Lithium; Mononuclear cells; Spinal cord injury (SCI); Umbilical cord blood