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:44
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
[21]   Semi-automated counting method of axons in transmission electron microscopic images [J].
Kim, Chan Yun ;
Rho, Seungsoo ;
Lee, Naeun ;
Lee, Chang-Kyu ;
Sung, Youngje .
VETERINARY OPHTHALMOLOGY, 2016, 19 (01) :29-37
[22]   Human chorionic-plate-derived mesenchymal stem cells and Wharton's jelly-derived mesenchymal stem cells: a comparative analysis of their potential as placenta-derived stem cells [J].
Kim, Mi Jeong ;
Shin, Kyung Seon ;
Jeon, Jin Hee ;
Lee, Dong Ryul ;
Shim, Sung Han ;
Kim, Jin Kyeoung ;
Cha, Dong-Hyun ;
Yoon, Tae Ki ;
Kim, Gi Jin .
CELL AND TISSUE RESEARCH, 2011, 346 (01) :53-64
[23]   Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms [J].
Kinnaird, T ;
Stabile, E ;
Burnett, MS ;
Lee, CW ;
Barr, S ;
Fuchs, S ;
Epstein, SE .
CIRCULATION RESEARCH, 2004, 94 (05) :678-685
[24]   Local delivery of marrow-derived stromal cells augments collateral perfusion through paracrine mechanisms [J].
Kinnaird, T ;
Stabile, E ;
Burnett, MS ;
Shou, M ;
Lee, CW ;
Barr, S ;
Fuchs, S ;
Epstein, SE .
CIRCULATION, 2004, 109 (12) :1543-1549
[25]   Upregulation of IGF-I in the goldfish retinal ganglion cells during the early stage of optic nerve regeneration [J].
Koriyama, Yoshiki ;
Homma, Keiko ;
Sugitani, Kayo ;
Higuchi, Yoshihiro ;
Matsukawa, Toru ;
Murayama, Daisuke ;
Kato, Satoru .
NEUROCHEMISTRY INTERNATIONAL, 2007, 50 (05) :749-756
[26]   Comparison of immunomodulatory effects of placenta mesenchymal stem cells with bone marrow and adipose mesenchymal stem cells [J].
Lee, Jung Min ;
Jung, Jieun ;
Lee, Hyun-Jung ;
Jeong, Su Jin ;
Cho, Kyung Jin ;
Hwang, Seong-Gyu ;
Kim, Gi Jin .
INTERNATIONAL IMMUNOPHARMACOLOGY, 2012, 13 (02) :219-224
[27]   Anti-Fibrotic Effect of Chorionic Plate-derived Mesenchymal Stem Cells Isolated from Human Placenta in a Rat Model of CCl4-injured Liver: Potential Application to the Treatment of Hepatic Diseases [J].
Lee, Min-Jae ;
Jung, Jieun ;
Na, Kyu-Hwan ;
Moon, Ji Suk ;
Lee, Hey-Jin ;
Kim, Jae-Hwan ;
Kim, Gwang Il ;
Kwon, Sung-Won ;
Hwang, Seong-Gyu ;
Kim, Gi Jin .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2010, 111 (06) :1453-1463
[28]   Stem and progenitor cells in human umbilical cord blood [J].
Lee, Myoung Woo ;
Jang, In Keun ;
Yoo, Keon Hee ;
Sung, Ki Woong ;
Koo, Hong Hoe .
INTERNATIONAL JOURNAL OF HEMATOLOGY, 2010, 92 (01) :45-51
[29]   Increased SCF/c-kit by hypoxia promotes autophagy of human placental chorionic plate-derived mesenchymal stem cells via regulating the phosphorylation of mTOR [J].
Lee, Youjin ;
Jung, Jieun ;
Cho, Kyung Jin ;
Lee, Seoung-Kwan ;
Park, Jong-Wan ;
Oh, Il-Hoan ;
Kim, Gi Jin .
JOURNAL OF CELLULAR BIOCHEMISTRY, 2013, 114 (01) :79-88
[30]   Intravitreal Injections of Neurotrophic Factors Secreting Mesenchymal Stem Cells Are Neuroprotective in Rat Eyes following Optic Nerve Transection [J].
Levkovitch-Verbin, Hani ;
Sadan, Ofer ;
Vander, Shelly ;
Rosner, Mordechai ;
Barhum, Yael ;
Melamed, Eldad ;
Offen, Daniel ;
Melamed, Shlomo .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2010, 51 (12) :6394-6400