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

被引:42
作者
Chung, Sokjoong [1 ]
Rho, Seungsoo [1 ]
Kim, Gijin [2 ]
Kim, So-Ra [2 ]
Baek, Kwang-Hyun [2 ]
Kang, Myungseo [3 ,4 ]
Lew, Helen [1 ]
机构
[1] CHA Univ, Dept Ophthalmol, CHA Bundang Med Ctr, 59 Yatap Ro, Songnam 463712, Gyeonggi Do, South Korea
[2] CHA Univ, Dept Biomed Sci, CHA Bundang Med Ctr, Songnam 463712, Gyeonggi Do, South Korea
[3] CHA Univ, Dept Lab Med, CHA Bundang Med Ctr, Songnam 463712, Gyeonggi Do, South Korea
[4] CHA Med Ctr Cord Blood Bank, Songnam, Gyeonggi Do, South Korea
基金
新加坡国家研究基金会;
关键词
optic nerve; placenta; stem cells; traumatic optic neuropathy; umbilical cord blood mononuclear cells; BONE-MARROW; HUMAN-PLACENTA; BRAIN-INJURY; PARACRINE MECHANISMS; NEUROTROPHIC FACTORS; PROGENITOR CELLS; CEREBRAL-PALSY; ISCHEMIC-HEART; IN-VITRO; REGENERATION;
D O I
10.3892/ijmm.2016.2532
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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-1 (HIF-1) 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-1. 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.
引用
收藏
页码:1170 / 1180
页数:11
相关论文
共 51 条
  • [1] Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes
    Alvarez-Dolado, M
    Pardal, R
    Garcia-Vardugo, JM
    Fike, JR
    Lee, HO
    Pfeffer, K
    Lois, C
    Morrison, SJ
    Alvarez-Buylla, A
    [J]. NATURE, 2003, 425 (6961) : 968 - 973
  • [2] Transplantation of cells from eye-like structures differentiated from embryonic stem cells in vitro and in vivo regeneration of retinal ganglion-like cells
    Aoki, Hitomi
    Hara, Akira
    Niwa, Masayuki
    Motohashi, Tsutomu
    Suzuki, Takashi
    Kunisada, Takahiro
    [J]. GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 2008, 246 (02) : 255 - 265
  • [3] Optic Nerve Regeneration
    Benowitz, Larry I.
    Yin, Yuqin
    [J]. ARCHIVES OF OPHTHALMOLOGY, 2010, 128 (08) : 1059 - 1064
  • [4] Booij Judith C, 2010, PLoS One, V5, pe9341, DOI 10.1371/journal.pone.0009341
  • [5] Human Muller stem cell (MIO-M1) transplantation in a rat model of glaucoma: Survival, differentiation, and integration
    Bull, Natalie D.
    Limb, G. Astrid
    Martin, Keith R.
    [J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2008, 49 (08) : 3449 - 3456
  • [6] Transplanted Oligodendrocyte Precursor Cells Reduce Neurodegeneration in a Model of Glaucoma
    Bull, Natalie D.
    Irvine, Karen-Amanda
    Franklin, Robin J. M.
    Martin, Keith R.
    [J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2009, 50 (09) : 4244 - 4253
  • [7] Characterization of dendritic cell differentiation pathways from cord blood CD34+CD7+CD45RA+ hematopoietic progenitor cells
    Canque, B
    Camus, S
    Dalloul, A
    Kahn, E
    Yagello, M
    Dezutter-Dambuyant, C
    Schmitt, D
    Schmitt, C
    Gluckman, JC
    [J]. BLOOD, 2000, 96 (12) : 3748 - 3756
  • [8] Engrafted chicken neural tube-derived stem cells support the innate propensity for axonal regeneration within the rat optic nerve
    Charalambous, Petar
    Hurst, Louise A.
    Thanos, Solon
    [J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2008, 49 (08) : 3513 - 3524
  • [9] Evolution of Human-Specific Neural SRGAP2 Genes by Incomplete Segmental Duplication
    Dennis, Megan Y.
    Nuttle, Xander
    Sudmant, Peter H.
    Antonacci, Francesca
    Graves, Tina A.
    Nefedov, Mikhail
    Rosenfeld, Jill A.
    Sajjadian, Saba
    Malig, Maika
    Kotkiewicz, Holland
    Curry, Cynthia J.
    Shafer, Susan
    Shaffer, Lisa G.
    de Jong, Pieter J.
    Wilson, Richard K.
    Eichler, Evan E.
    [J]. CELL, 2012, 149 (04) : 912 - 922
  • [10] Estimation of axon counts in a rat model of glaucoma: comparison of fixed-pattern sampling with targeted sampling
    Ebneter, Andreas
    Casson, Robert J.
    Wood, John Pm
    Chidlow, Glyn
    [J]. CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 2012, 40 (06) : 626 - 633