title: Human umbilical cord blood mononuclear cells and chorionic plate-derived mesenchymal stem cells promote axon survival in a rat model of optic nerve crush injury.
abstract: The use of mesenchymal stem cells (MSCs) in cell therapy in regenerative medicine has great potential, particularly in the treatment of nerve injury. Umbilical cord blood (UCB) reportedly contains stem cells, which have been widely used as a hematopoietic source and may have therapeutic potential for neurological impairment. Although ongoing research is dedicated to the management of traumatic optic nerve injury using various measures, novel therapeutic strategies based on the complex underlying mechanisms responsible for optic nerve injury, such as inflammation and/or ischemia, are required. In the present study, a rat model of optic nerve crush (ONC) injury was established in order to examine the effects of transplanting human chorionic plate-derived MSCs (CP‑MSCs) isolated from the placenta, as well as human UCB mononuclear cells (CB-MNCs) on compressed rat optic nerves. Expression markers for inflammation, apoptosis, and optic nerve regeneration were analyzed, as well as the axon survival rate by direct counting. Increased axon survival rates were observed following the injection of CB‑MNCs at at 1 week post-transplantation compared with the controls. The levels of growth-associated protein-43 (GAP‑43) were increased after the injection of CB‑MNCs or CP‑MSCs compared with the controls, and the expression levels of hypoxia-inducible factor-1α (HIF-1α) were also significantly increased following the injection of CB-MNCs or CP-MSCs. ERM-like protein (ERMN) and SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2) were found to be expressed in the optic nerves of the CP‑MSC-injected rats with ONC injury. The findings of our study suggest that the administration of CB‑MNCs or CP‑MSCs may promote axon survival through systemic concomitant mechanisms involving GAP‑43 and HIF‑1α. Taken together, these findings provide further understanding of the mechanisms repsonsible for optic nerve injury and may aid in the development of novel cell-based therapeutic strategies with future applications in regenerative medicine, particularly in the management of optic nerve disorders.
authors.affiliation: Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Sokjoong
authors.initials: S
authors.lastname: Chung
authors.affiliation: Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Seungsoo
authors.initials: S
authors.lastname: Rho
authors.affiliation: Department of Biomedical Science, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Gijin
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: So-Ra
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Baek
authors.affiliation: Department of Laboratory Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Myungseo
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Helen
authors.initials: H
authors.lastname: Lew
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D015415:Biomarkers; D002470:Cell Survival; D000071576:Crush Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D016130:Immunophenotyping; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000637:transplantation; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009416:Nerve Regeneration; D020221:Optic Nerve Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011247:Pregnancy; D051381:Rats
chemical_list: D015415:Biomarkers; D019922:GAP-43 Protein; D051795:Hypoxia-Inducible Factor 1, alpha Subunit