Win-Ping Deng1, Chi-Chiang Yang2, Liang-Yo Yang3, Chun-Wei D Chen4, Wei-Hong Chen1, Charn-Bing Yang5, Yu-Hsin Chen3, Wen-Fu T Lai6, Perry F Renshaw7. 1. Graduate Institute of Biomedical Materials and Engineering, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan. 2. Department of Neurology, Tungs' Taichung Metroharbor Hospital, 699 Taiwan Blvd. 8 Sec., Taitung, Taiwan. 3. Department of Physiology, College of Medicine, Taipei Medical University, 250 Wu-Hsing Street, Taipei, Taiwan. 4. Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, 415 E. 68th Street, New York 10065, NY, USA. 5. Orthopedic Section Department, New Taipei City Hospital, 198 Yin-His Rd., Banquiao District, New Taipei City, Taiwan. 6. 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. 7. The Brain Institute, The University of Utah, 201 Presidents Cir, Salt Lake City 84112, UT, USA.
Abstract
BACKGROUND CONTEXT: 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. PURPOSE: 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. STUDY DESIGN: 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.
BACKGROUND CONTEXT: 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. PURPOSE: 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. STUDY DESIGN: 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: D M Basso; M S Beattie; J C Bresnahan; D K Anderson; A I Faden; J A Gruner; T R Holford; C Y Hsu; L J Noble; R Nockels; P L Perot; S K Salzman; W Young Journal: J Neurotrauma Date: 1996-07 Impact factor: 5.269
Authors: Jun Nyung Lee; Tae Gyun Kwon; Jung Yeon Kim; So Young Chun; Jin-Sung Park; Jae-Wook Chung; Yun-Sok Ha Journal: Tissue Eng Regen Med Date: 2017-12-28 Impact factor: 4.451