Assessment of Glial Scar, Tissue Sparing, Behavioral Recovery and Axonal Regeneration following Acute Transplantation of Genetically Modified Human Umbilical Cord Blood Cells in a Rat Model of Spinal Cord Contusion
Yana O Mukhamedshina, Ekaterina E Garanina, Galina A Masgutova, Luisa R Galieva, Elvira R Sanatova, Yurii A Chelyshev, Albert A Rizvanov, Yana O Mukhamedshina, Ekaterina E Garanina, Galina A Masgutova, Luisa R Galieva, Elvira R Sanatova, Yurii A Chelyshev, Albert A Rizvanov
Abstract
Objective and methods: This study investigated the potential for protective effects of human umbilical cord blood mononuclear cells (UCB-MCs) genetically modified with the VEGF and GNDF genes on contusion spinal cord injury (SCI) in rats. An adenoviral vector was constructed for targeted delivery of VEGF and GDNF to UCB-MCs. Using a rat contusion SCI model we examined the efficacy of the construct on tissue sparing, glial scar severity, the extent of axonal regeneration, recovery of motor function, and analyzed the expression of the recombinant genes VEGF and GNDF in vitro and in vivo.
Results: Transplantation of UCB-MCs transduced with adenoviral vectors expressing VEGF and GDNF at the site of SCI induced tissue sparing, behavioral recovery and axonal regeneration comparing to the other constructs tested. The adenovirus encoding VEGF and GDNF for transduction of UCB-MCs was shown to be an effective and stable vehicle for these cells in vivo following the transplantation into the contused spinal cord.
Conclusion: Our results show that a gene delivery using UCB-MCs-expressing VEGF and GNDF genes improved both structural and functional parameters after SCI. Further histological and behavioral studies, especially at later time points, in animals with SCI after transplantation of genetically modified UCB-MCs (overexpressing VEGF and GDNF genes) will provide additional insight into therapeutic potential of such cells.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
Figures
![Fig 1. VEGF, GDNF and EGFP mRNA…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4803326/bin/pone.0151745.g001.jpg)
Fig 2. VEGF, GDNF and EGFP mRNA…
Fig 2. VEGF, GDNF and EGFP mRNA expression in vivo.
VEGF, GDNF (A) and EGFP…
Fig 3. Tissue analysis in experimental groups.
Fig 3. Tissue analysis in experimental groups.
Injured spinal cord 30 days after SCI without…
Fig 4. Visualization of grafted cells at…
Fig 4. Visualization of grafted cells at day 30 after transplantation.
Visualization of grafted cells…
Fig 5. Glial scar formation at the…
Fig 5. Glial scar formation at the lesion site indicated by GFAP.
Visualization of glial…
Fig 6. Expression of GFAP, CGRP and…
Fig 6. Expression of GFAP, CGRP and GAP43 in the lesion site of spinal cord.
Fig 7. BBB locomotor scores of rats…
Fig 7. BBB locomotor scores of rats after SCI or Sham in experimental group.
BBB…
- Electrophysiological, Morphological, and Ultrastructural Features of the Injured Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes.Mukhamedshina YO, Gilazieva ZE, Arkhipova SS, Galieva LR, Garanina EE, Shulman AA, Yafarova GG, Chelyshev YA, Shamsutdinova NV, Rizvanov AA. Mukhamedshina YO, et al. Neural Plast. 2017;2017:9857918. doi: 10.1155/2017/9857918. Epub 2017 Mar 21. Neural Plast. 2017. PMID: 28421147 Free PMC article.
- Adenoviral vector carrying glial cell-derived neurotrophic factor for direct gene therapy in comparison with human umbilical cord blood cell-mediated therapy of spinal cord injury in rat.Mukhamedshina YO, Shaymardanova GF, Garanina ЕЕ, Salafutdinov II, Rizvanov АА, Islamov RR, Chelyshev YA. Mukhamedshina YO, et al. Spinal Cord. 2016 May;54(5):347-59. doi: 10.1038/sc.2015.161. Epub 2015 Sep 29. Spinal Cord. 2016. PMID: 26415641
- Gene transfer of glial cell line-derived neurotrophic factor promotes functional recovery following spinal cord contusion.Tai MH, Cheng H, Wu JP, Liu YL, Lin PR, Kuo JS, Tseng CJ, Tzeng SF. Tai MH, et al. Exp Neurol. 2003 Oct;183(2):508-15. doi: 10.1016/s0014-4886(03)00130-4. Exp Neurol. 2003. PMID: 14552891
- Bone marrow mesenchymal stem cells (BMSCs) improved functional recovery of spinal cord injury partly by promoting axonal regeneration.Lin L, Lin H, Bai S, Zheng L, Zhang X. Lin L, et al. Neurochem Int. 2018 May;115:80-84. doi: 10.1016/j.neuint.2018.02.007. Epub 2018 Feb 16. Neurochem Int. 2018. PMID: 29458076 Review.
- [The role of glial scar on axonal regeneration after spinal cord injury].Li X, Li J, Xiao Z, Dai J. Li X, et al. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2018 Aug 15;32(8):973-978. doi: 10.7507/1002-1892.201806093. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2018. PMID: 30238720 Free PMC article. Review. Chinese.
-
- Kuh SU, Cho YE, Yoon DH, Kim KN, Ha Y. Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat. Acta Neurochirurgica (Wien). 2005;147(9): 985–992. - PubMed
-
- Yan HB, Zhang ZM, Jin DD, Wang XJ, Lu KW. The repair of acute spinal cord injury in rats by olfactory ensheathing cells graft modified by glia cell line–derived neurotrophic factor gene in combination with the injection of monoclonal antibody IN–1. Zhonghua Wai Ke Za Zhi. 2009;47(23): 1817–1820. - PubMed
- Research Support, Non-U.S. Gov't
- Animals
- Axons / physiology
- Cicatrix
- Disease Models, Animal
- Female
- Fetal Blood / cytology
- Gene Transfer Techniques
- Genetic Therapy / methods*
- Glial Cell Line-Derived Neurotrophic Factor / biosynthesis
- Glial Cell Line-Derived Neurotrophic Factor / genetics*
- Green Fluorescent Proteins / genetics
- Humans
- Leukocytes, Mononuclear / cytology
- Leukocytes, Mononuclear / transplantation*
- Male
- Motor Activity / physiology
- Nerve Regeneration / physiology*
- Neuroglia / pathology
- RNA, Messenger / biosynthesis
- Random Allocation
- Rats
- Rats, Wistar
- Recovery of Function / physiology
- Spinal Cord
- Spinal Cord Injuries / physiopathology
- Spinal Cord Injuries / therapy*
- Transplantation, Heterologous
- Vascular Endothelial Growth Factor A / biosynthesis
- Vascular Endothelial Growth Factor A / genetics*
- GDNF protein, human
- Glial Cell Line-Derived Neurotrophic Factor
- RNA, Messenger
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- enhanced green fluorescent protein
- Green Fluorescent Proteins
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Fig 2. VEGF, GDNF and EGFP mRNA…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4803326/bin/pone.0151745.g002.jpg)
Fig 3. Tissue analysis in experimental groups.
Fig 3. Tissue analysis in experimental groups.
Injured spinal cord 30 days after SCI without…
Fig 4. Visualization of grafted cells at…
Fig 4. Visualization of grafted cells at day 30 after transplantation.
Visualization of grafted cells…
Fig 5. Glial scar formation at the…
Fig 5. Glial scar formation at the lesion site indicated by GFAP.
Visualization of glial…
Fig 6. Expression of GFAP, CGRP and…
Fig 6. Expression of GFAP, CGRP and GAP43 in the lesion site of spinal cord.
Fig 7. BBB locomotor scores of rats…
Fig 7. BBB locomotor scores of rats after SCI or Sham in experimental group.
BBB…
- Electrophysiological, Morphological, and Ultrastructural Features of the Injured Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes.Mukhamedshina YO, Gilazieva ZE, Arkhipova SS, Galieva LR, Garanina EE, Shulman AA, Yafarova GG, Chelyshev YA, Shamsutdinova NV, Rizvanov AA. Mukhamedshina YO, et al. Neural Plast. 2017;2017:9857918. doi: 10.1155/2017/9857918. Epub 2017 Mar 21. Neural Plast. 2017. PMID: 28421147 Free PMC article.
- Adenoviral vector carrying glial cell-derived neurotrophic factor for direct gene therapy in comparison with human umbilical cord blood cell-mediated therapy of spinal cord injury in rat.Mukhamedshina YO, Shaymardanova GF, Garanina ЕЕ, Salafutdinov II, Rizvanov АА, Islamov RR, Chelyshev YA. Mukhamedshina YO, et al. Spinal Cord. 2016 May;54(5):347-59. doi: 10.1038/sc.2015.161. Epub 2015 Sep 29. Spinal Cord. 2016. PMID: 26415641
- Gene transfer of glial cell line-derived neurotrophic factor promotes functional recovery following spinal cord contusion.Tai MH, Cheng H, Wu JP, Liu YL, Lin PR, Kuo JS, Tseng CJ, Tzeng SF. Tai MH, et al. Exp Neurol. 2003 Oct;183(2):508-15. doi: 10.1016/s0014-4886(03)00130-4. Exp Neurol. 2003. PMID: 14552891
- Bone marrow mesenchymal stem cells (BMSCs) improved functional recovery of spinal cord injury partly by promoting axonal regeneration.Lin L, Lin H, Bai S, Zheng L, Zhang X. Lin L, et al. Neurochem Int. 2018 May;115:80-84. doi: 10.1016/j.neuint.2018.02.007. Epub 2018 Feb 16. Neurochem Int. 2018. PMID: 29458076 Review.
- [The role of glial scar on axonal regeneration after spinal cord injury].Li X, Li J, Xiao Z, Dai J. Li X, et al. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2018 Aug 15;32(8):973-978. doi: 10.7507/1002-1892.201806093. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2018. PMID: 30238720 Free PMC article. Review. Chinese.
-
- Kuh SU, Cho YE, Yoon DH, Kim KN, Ha Y. Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat. Acta Neurochirurgica (Wien). 2005;147(9): 985–992. - PubMed
-
- Yan HB, Zhang ZM, Jin DD, Wang XJ, Lu KW. The repair of acute spinal cord injury in rats by olfactory ensheathing cells graft modified by glia cell line–derived neurotrophic factor gene in combination with the injection of monoclonal antibody IN–1. Zhonghua Wai Ke Za Zhi. 2009;47(23): 1817–1820. - PubMed
- Research Support, Non-U.S. Gov't
- Animals
- Axons / physiology
- Cicatrix
- Disease Models, Animal
- Female
- Fetal Blood / cytology
- Gene Transfer Techniques
- Genetic Therapy / methods*
- Glial Cell Line-Derived Neurotrophic Factor / biosynthesis
- Glial Cell Line-Derived Neurotrophic Factor / genetics*
- Green Fluorescent Proteins / genetics
- Humans
- Leukocytes, Mononuclear / cytology
- Leukocytes, Mononuclear / transplantation*
- Male
- Motor Activity / physiology
- Nerve Regeneration / physiology*
- Neuroglia / pathology
- RNA, Messenger / biosynthesis
- Random Allocation
- Rats
- Rats, Wistar
- Recovery of Function / physiology
- Spinal Cord
- Spinal Cord Injuries / physiopathology
- Spinal Cord Injuries / therapy*
- Transplantation, Heterologous
- Vascular Endothelial Growth Factor A / biosynthesis
- Vascular Endothelial Growth Factor A / genetics*
- GDNF protein, human
- Glial Cell Line-Derived Neurotrophic Factor
- RNA, Messenger
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- enhanced green fluorescent protein
- Green Fluorescent Proteins
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Fig 3. Tissue analysis in experimental groups.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4803326/bin/pone.0151745.g003.jpg)
![Fig 4. Visualization of grafted cells at…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4803326/bin/pone.0151745.g004.jpg)
![Fig 5. Glial scar formation at the…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4803326/bin/pone.0151745.g005.jpg)
Fig 6. Expression of GFAP, CGRP and…
Fig 6. Expression of GFAP, CGRP and GAP43 in the lesion site of spinal cord.
Fig 7. BBB locomotor scores of rats…
Fig 7. BBB locomotor scores of rats after SCI or Sham in experimental group.
BBB…
- Electrophysiological, Morphological, and Ultrastructural Features of the Injured Spinal Cord Tissue after Transplantation of Human Umbilical Cord Blood Mononuclear Cells Genetically Modified with the VEGF and GDNF Genes.Mukhamedshina YO, Gilazieva ZE, Arkhipova SS, Galieva LR, Garanina EE, Shulman AA, Yafarova GG, Chelyshev YA, Shamsutdinova NV, Rizvanov AA. Mukhamedshina YO, et al. Neural Plast. 2017;2017:9857918. doi: 10.1155/2017/9857918. Epub 2017 Mar 21. Neural Plast. 2017. PMID: 28421147 Free PMC article.
- Adenoviral vector carrying glial cell-derived neurotrophic factor for direct gene therapy in comparison with human umbilical cord blood cell-mediated therapy of spinal cord injury in rat.Mukhamedshina YO, Shaymardanova GF, Garanina ЕЕ, Salafutdinov II, Rizvanov АА, Islamov RR, Chelyshev YA. Mukhamedshina YO, et al. Spinal Cord. 2016 May;54(5):347-59. doi: 10.1038/sc.2015.161. Epub 2015 Sep 29. Spinal Cord. 2016. PMID: 26415641
- Gene transfer of glial cell line-derived neurotrophic factor promotes functional recovery following spinal cord contusion.Tai MH, Cheng H, Wu JP, Liu YL, Lin PR, Kuo JS, Tseng CJ, Tzeng SF. Tai MH, et al. Exp Neurol. 2003 Oct;183(2):508-15. doi: 10.1016/s0014-4886(03)00130-4. Exp Neurol. 2003. PMID: 14552891
- Bone marrow mesenchymal stem cells (BMSCs) improved functional recovery of spinal cord injury partly by promoting axonal regeneration.Lin L, Lin H, Bai S, Zheng L, Zhang X. Lin L, et al. Neurochem Int. 2018 May;115:80-84. doi: 10.1016/j.neuint.2018.02.007. Epub 2018 Feb 16. Neurochem Int. 2018. PMID: 29458076 Review.
- [The role of glial scar on axonal regeneration after spinal cord injury].Li X, Li J, Xiao Z, Dai J. Li X, et al. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2018 Aug 15;32(8):973-978. doi: 10.7507/1002-1892.201806093. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2018. PMID: 30238720 Free PMC article. Review. Chinese.
-
- Kuh SU, Cho YE, Yoon DH, Kim KN, Ha Y. Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat. Acta Neurochirurgica (Wien). 2005;147(9): 985–992. - PubMed
-
- Yan HB, Zhang ZM, Jin DD, Wang XJ, Lu KW. The repair of acute spinal cord injury in rats by olfactory ensheathing cells graft modified by glia cell line–derived neurotrophic factor gene in combination with the injection of monoclonal antibody IN–1. Zhonghua Wai Ke Za Zhi. 2009;47(23): 1817–1820. - PubMed
- Research Support, Non-U.S. Gov't
- Animals
- Axons / physiology
- Cicatrix
- Disease Models, Animal
- Female
- Fetal Blood / cytology
- Gene Transfer Techniques
- Genetic Therapy / methods*
- Glial Cell Line-Derived Neurotrophic Factor / biosynthesis
- Glial Cell Line-Derived Neurotrophic Factor / genetics*
- Green Fluorescent Proteins / genetics
- Humans
- Leukocytes, Mononuclear / cytology
- Leukocytes, Mononuclear / transplantation*
- Male
- Motor Activity / physiology
- Nerve Regeneration / physiology*
- Neuroglia / pathology
- RNA, Messenger / biosynthesis
- Random Allocation
- Rats
- Rats, Wistar
- Recovery of Function / physiology
- Spinal Cord
- Spinal Cord Injuries / physiopathology
- Spinal Cord Injuries / therapy*
- Transplantation, Heterologous
- Vascular Endothelial Growth Factor A / biosynthesis
- Vascular Endothelial Growth Factor A / genetics*
- GDNF protein, human
- Glial Cell Line-Derived Neurotrophic Factor
- RNA, Messenger
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
- enhanced green fluorescent protein
- Green Fluorescent Proteins
- Full Text Sources
- Other Literature Sources
- Medical
![Fig 6. Expression of GFAP, CGRP and…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4803326/bin/pone.0151745.g006.jpg)
![Fig 7. BBB locomotor scores of rats…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4803326/bin/pone.0151745.g007.jpg)
References
- Kuh SU, Cho YE, Yoon DH, Kim KN, Ha Y. Functional recovery after human umbilical cord blood cells transplantation with brain-derived neutrophic factor into the spinal cord injured rat. Acta Neurochirurgica (Wien). 2005;147(9): 985–992.
- Yan HB, Zhang ZM, Jin DD, Wang XJ, Lu KW. The repair of acute spinal cord injury in rats by olfactory ensheathing cells graft modified by glia cell line–derived neurotrophic factor gene in combination with the injection of monoclonal antibody IN–1. Zhonghua Wai Ke Za Zhi. 2009;47(23): 1817–1820.
- Kim HM, Hwang DH, Lee JE, Kim SU, Kim BG. Ex vivo VEGF delivery by neural stem cells enhances proliferation of glial progenitors, angiogenesis, and tissue sparing after spinal cord injury. PLoS One. 2009;4(3): 1–10.
- Lin WP, Chen XW, Zhang LQ, Wu CY, Huang ZD, Lin JH.Effect of neuroglobin genetically modified bone marrow mesenchymal stem cells transplantation on spinal cord injury in rabbits. PLoS One. 2013;8(5): 1–9.
- Jones LL, Oudega M, Bunge MB, Tuszynski MH. Neurotrophic factors, cellular bridges and gene therapy for spinal cord injury. J Physiol. 2001;533(1): 83–89.
- Gluckman E, Locatelli F. Umbilical cord blood transplants. Opin Hematol. 2000;7(6): 353–357.
- Weiss M, Troyer D. Stem cells in the umbilical cord. Stem Cell Rev. 2007;2: 155–162.
- Park SI, Lim JY, Jeong CH, Kim SM, Jun JA, Jeun SS, et al. Human umbilical cord blood-derived mesenchymal stem cell therapy promotes functional recovery of contused rat spinal cord through enhancement of endogenous cell proliferation and oligogenesis. J Biomed Biotechnol. 2012: 1–8.
- Rodrigues LP, Iglesias D, Nicola FC, Steffens D, Valentim L, Witczak A, et al. Transplantation of mononuclear cells from human umbilical cord blood promotes functional recovery after traumatic spinal cord injury in Wistar rats. Braz J Med Biol Res. 2012;45(1): 49–57.
- Mukhamedshina YO, Shaymardanova GF, Garanina EE, Salafutdinov II, Rizvanov AA, Islamov RR, et al. Adenoviral vector carrying glial cell-derived neurotrophic factor for direct gene therapy or human umbilical cord blood cell-mediated therapy of spinal cord injury in rat. Spinal Cord. 2015. September 29 10.1038/sc.2015.161 [Epub ahead of print]
- Ikeda YN, Fukuda M, Wada T, Matsumoto A, Satomi S, Yokoyama S, et al. Development of angiogenic cell and gene therapy by transplantation of umbilical cord blood with vascular endothelial growth factor gene. Hypertens Res. 2004;27(2): 119–128.
- Cheng H, Wu JP, Tzeng SF. Neuroprotection of glial cell line–derived neurotrophic factor in damaged spinal cords following contusive injury. Neurosci Res. 2002;69(3): 397–405.
- Islamov RR, Chintalgattu V, Pak ES. Induction of VEGF and its Flt-1 receptor after sciatic nerve crush injury. Neuroreport. 2004;15(13): 2117–2121.
- Mackenzie F, MacRuhrberg C. Diverse roles for VEGF–A in the nervous system. Development. 2012;139(8): 1371–1380. 10.1242/dev.072348
- Rosenstein JM, Mani N, Silverman WF, Krum JM. Patterns of brain angiogenesis after vascular endothelial growth factor administration in vitro and in vivo. Proc Natl Acad Sci USA. 1998;95(12): 7086–7091.
- Jin H, Liu ML, Kim HA, Lee M, An S, Oh J, et al. Role of the oxygen–dependent degradation domain in a hypoxia–inducible gene expression system in vascular endothelial growth factor gene therapy. Spine. 2009;34(26): 952–958.
- Sondell M, Sundler F, Kanje M. Vascular endothelial growth factor is a neurotrophic factor which stimulates axonal outgrowth through the flk–1 receptor. Eur J Neurosci. 2004;12: 4243–4254.
- Mills CD, Allchorne AJ, Griffin RS, Woolf CJ, Costigan M. GDNF selectively promotes regeneration of injury–primed sensory neurons in the lesioned spinal cord. Mol Cell Neurosci.2007;36(2): 185–194.
- Islamov RR, Rizvanov AA, Mukhamedyarov MA, Salafutdinov II, Garanina EE, Fedotova VY, et al. Symptomatic Improvement, Increased Life-Span and Sustained Cell Homing in Amyotrophic Lateral Sclerosis After Transplantation of Human Umbilical Cord Blood Cells Genetically Modified with Adeno-Viral Vectors Expressing a Neuro-Protective Factor and a Neural Cell Adhesion Molecule. Curr Gene Ther. 2015;15(3): 266–276.
- Lebedev SV, Timofeyev SV, Zharkov AV, Schipilov VG, Chelyshev JA, Masgutova GA, et al. Exercise tests and BBB method for evaluation of motor disorders in rats after contusion spinal injury. Bull Exp Biol Med. 2008;146(4): 489–494.
- Mukhamedshina YO, Shaymardanova GF, Muhitov AR, Salafutdinov II, Rizvanov AA, Zarubina VN, et al. Survival and differentiation of endogenous Schwann cells migrating into spinal cord under the influence of neurotrophic factors. Cellular Transplantation and Tissue Engineering. 2012;7(3): 125–129.
- Barbour HR, Plant CD, Harvey AR, Plant GW. Tissue sparing, behavioral recovery, supraspinal axonal sparing/regeneration following sub-acute glial transplantation in a model of spinal cord contusion. BMC Neurosci. 2013. September 27;14:106 10.1186/1471-2202-14-106
- Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12(1): 1–21.
- Zhang L, Ma Z, Smith GM, Wen X, Pressman Y, et al. GDNF-enhanced axonal regeneration and myelination following spinal cord injury is mediated by primary effects on neurons. Glia. 2009;57(11): 1178–1191. 10.1002/glia.20840
- Sondell M, Lundborg G, Kanje M. Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system. Neurosci. 1999;19(14): 5731–5740.
- Deng LX, Hu J, Liu N, Wang X, Smith GM, Wen X, et al. GDNF modifies reactive astrogliosis allowing robust axonal regeneration through Schwann cell-seeded guidance channels after spinal cord injury. Exp Neurol. 2011;229(2): 238–250. 10.1016/j.expneurol.2011.02.001
- Lutton C, Young YW, Williams R, Meedeniya AC, Mackay-Sim A, Goss B. Combined VEGF and PDGF treatment reduces secondary degeneration after spinal cord injury. J Neurotrauma. 2012;29(5): 957–970. 10.1089/neu.2010.1423
- Antonic A, Sena ES, Lees JS, Wills TE, Skeers P, Batchelor PE, et al. Stem cell transplantation in traumatic spinal cord injury: a systematic review and meta-analysis of animal studies. PLoS Biol. 2013;11(12): 1–14.
Source: PubMed