title: Extracellular matrix-regulated neural differentiation of human multipotent marrow progenitor cells enhances functional recovery after spinal cord injury.
abstract: BACKGROUND
  Recent advanced studies have demonstrated that cytokines and extracellular matrix (ECM) could trigger various types of neural differentiation. However, the efficacy of differentiation and in vivo transplantation has not yet thoroughly been investigated.
  
  
  OBJECTIVE
  To highlight the current understanding of the effects of ECM on neural differentiation of human bone marrow-derived multipotent progenitor cells (MPCs), regarding state-of-art cure for the animal with acute spinal cord injury (SCI), and explore future treatments aimed at neural repair.
  
  
  METHODS
  A selective overview of the literature pertaining to the neural differentiation of the MSCs and experimental animals aimed at improved repair of SCI.
  
  
  METHODS
  Extracellular matrix proteins, tenascin-cytotactin (TN-C), tenascin-restrictin (TN-R), and chondroitin sulfate (CS), with the cytokines, nerve growth factor (NGF)/brain-derived neurotrophic factor (BDNF)/retinoic acid (RA) (NBR), were incorporated to induce transdifferentiation of human MPCs. Cells were treated with NBR for 7 days, and then TN-C, TN-R, or CS was added for 2 days. The medium was changed every 2 days. Twenty-four animals were randomly assigned to four groups with six animals in each group: one experimental and three controls. Animals received two (bilateral) injections of vehicle, MPCs, NBR-induced MPCs, or NBR/TN-C-induced MPCs into the lesion sites after SCI. Functional assessment was measured using the Basso, Beattie, and Bresnahan locomotor rating score. Data were analyzed using analysis of variance followed by Student-Newman-Keuls (SNK) post hoc tests.
  
  
  RESULTS
  Results showed that MPCs with the transdifferentiation of human MPCs to neurons were associated with increased messenger-RNA (mRNA) expression of neuronal markers including nestin, microtubule-associated protein (MAP) 2, glial fibrillary acidic protein, βIII tubulin, and NGF. Greater amounts of neuronal morphology appeared in cultures incorporated with TN-C and TN-R than those with CS. The addition of TN-C enhanced mRNA expressions of MAP2, βIII tubulin, and NGF, whereas TN-R did not significantly change. Conversely, CS exposure decreased MAP2, βIII tubulin, and NGF expressions. The TN-C-treated MSCs significantly and functionally repaired SCI-induced rats at Day 42. Present results indicate that ECM components, such as tenascins and CS in addition to cytokines, may play functional roles in regulating neurogenesis by human MPCs.
  
  
  CONCLUSIONS
  These findings suggest that the combined use of TN-C, NBR, and human MPCs offers a new feasible method for nerve repair.
authors.affiliation: Graduate Institute of Biomedical Materials and Engineering, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
authors.forename: Win-Ping
authors.initials: WP
authors.lastname: Deng
authors.affiliation: Department of Neurology, Tungs' Taichung Metroharbor Hospital, 699 Taiwan Blvd. 8 Sec., Taitung, Taiwan.
authors.forename: Chi-Chiang
authors.initials: CC
authors.lastname: Yang
authors.affiliation: Department of Physiology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
authors.forename: Liang-Yo
authors.initials: LY
authors.lastname: Yang
authors.affiliation: Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 415 E. 68th Street, New York 10065, NY, USA.
authors.forename: Chun-Wei D
authors.initials: CW
authors.lastname: Chen
authors.affiliation: Graduate Institute of Biomedical Materials and Engineering, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Chen
authors.affiliation: Orthopedic Section Department, New Taipei City Hospital, 198 Yin-His Rd., Banquiao District, New Taipei City, Taiwan.
authors.forename: Charn-Bing
authors.initials: CB
authors.lastname: Yang
authors.affiliation: Department of Physiology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan.
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 415 E. 68th Street, New York 10065, NY, USA; International Center of Nano Biomedicine Research, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan; Brain McLean Imaging Center, McLean Hospital/Harvard Medical School, 115 Mill Strret, Belmont 02115, MA, USA. Electronic address: laitw@tmu.edu.tw.
authors.forename: Wen-Fu T
authors.initials: WF
authors.lastname: Lai
authors.affiliation: The Brain Institute, The University of Utah, 201 Presidents Cir, Salt Lake City 84112, UT, USA.
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D054338:Cell Transdifferentiation / Q000187:drug effects* / Q000502:physiology; D002809:Chondroitin Sulfates / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D019063:Tenascin / Q000494:pharmacology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D019063:Tenascin; C074638:tenascin R; D002809:Chondroitin Sulfates; D020932:Nerve Growth Factor
keywords: Chondroitin sulfate; Extracellular matrix; Human multipotent progenitor cells; Neurogenesis; Tenascin-cytotactin; Tenascin-restrictin