Effect of transplantation of olfactory ensheathing cell conditioned medium induced bone marrow stromal cells on rats with spinal cord injury

Feng,Linjie; Gan,Hongquan; Zhao,Wenguo; Liu,Yingjie

doi:10.3892/mmr.2017.6811

Effect of transplantation of olfactory ensheathing cell conditioned medium induced bone marrow stromal cells on rats with spinal cord injury

Authors:
- Linjie Feng
- Hongquan Gan
- Wenguo Zhao
- Yingjie Liu
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Affiliations: Department of Orthopedics, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei 063000, P.R. China
Published online on: June 20, 2017 https://doi.org/10.3892/mmr.2017.6811
Pages: 1661-1668
Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Spinal cord injury is a serious threat to human health and various techniques have been deployed to ameliorate or cure its effects. Stem cells transplantation is one of the promising methods. The primary aim of the present study was to investigate the effect of the transplantation of olfactory ensheathing cell (OEC) conditioned medium‑induced bone marrow stromal cells (BMSCs) on spinal cord injury. Rat spinal cord compression injury animal models were generated, and the rats divided into the following three groups: Group A, (control) Dulbecco's modified Eagle's medium‑treated group; group B, normal BMSC‑treated group; group C, OEC conditioned medium‑induced BMSC‑treated group. The animals were sacrificed at 2, 4 and 8 weeks following transplantation for hematoxylin and eosin staining, and fluorescence staining of neurofilament protein, growth associated protein‑43 and neuron‑specific nuclear protein. The cavity area of the spinal cord injury was significantly reduced at 2 and 4 weeks following transplantation in group C, and a significant difference between the Basso, Beattie and Bresnahan score in group C and groups A and B was observed. Regenerated nerve fibers were observed in groups B and C; however, a greater number of regenerated nerve fibers were observed in group C. BMSCs induced by OEC conditioned medium survived in vivo, significantly reduced the cavity area of spinal cord injury, promoted nerve fiber regeneration following spinal cord injury and facilitated recovery of motor function. The present study demonstrated a novel method to repair spinal cord injury by using induced BMSCs, with satisfactory results.

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1	Bonner JF and Steward O: Repair of spinal cord injury with neuronal relays: From fetal grafts to neural stem cells. Brain Res. 1619:115–123. 2015. View Article : Google Scholar : PubMed/NCBI
2	Taoka Y and Okajima K: Spinal cord injury in the rat. Prog Neurobiol. 56:341–358. 1998. View Article : Google Scholar : PubMed/NCBI
3	Ankeny DP, McTigue DM and Jakeman LB: Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol. 190:17–31. 2004. View Article : Google Scholar : PubMed/NCBI
4	Qiu XC, Jin H, Zhang RY, Ding Y, Zeng X, Lai BQ, Ling EA, Wu JL and Zeng YS: Donor mesenchymal stem cell-derived neural-like cells transdifferentiate into myelin-forming cells and promote axon regeneration in rat spinal cord transaction. Stem Cell Res Ther. 6:1052015. View Article : Google Scholar : PubMed/NCBI
5	Collyer E, Catenaccio A, Lemaitre D, Diaz P, Valenzuela V, Bronfman F and Court FA: Sprouting of axonal collaterals after spinal cord injury is prevented by delayed axonal degeneration. Exp Neurol. 261:451–461. 2014. View Article : Google Scholar : PubMed/NCBI
6	Plunet WT, Streijger F, Lam CK, Lee JH, Liu J and Tetzlaff W: Dietary restriction started after spinal cord injury improves functional recovery. Exp Neurol. 213:28–35. 2008. View Article : Google Scholar : PubMed/NCBI
7	Slotkin JR, Pritchard CD, Luque B, Ye J, Layer RT, Lawrence MS, O'Shea TM, Roy RR, Zhong H, Vollenweider I, et al: Biodegradable scaffolds promote tissue remodeling and functional improvement in non-human primates with acute spinal cord injury. Biomaterials. 123:63–76. 2017. View Article : Google Scholar : PubMed/NCBI
8	Deng LX, Walker C and Xu XM: Schwann cell transplantation and descending propriospinal regeneration after spinal cord injury. Brain Res. 1619:104–114. 2015. View Article : Google Scholar : PubMed/NCBI
9	Nakano N, Nakai Y, Seo TB, Homma T, Yamada Y, Ohta M, Suzuki Y, Nakatani T, Fukushima M, Hayashibe M and Ide C: Effects of bone marrow stromal cell transplantation through CSF on the subacute and chronic spinal cord injury in rats. PLoS One. 8:e734942013. View Article : Google Scholar : PubMed/NCBI
10	Tharion G, Indirani K, Durai M, Meenakshi M, Devasahayam SR, Prabhav NR, Solomons C and Bhattacharji S: Motor recovery following olfactory ensheathing cell transplantation in rats with spinal cord injury. Neurol India. 59:566–572. 2011. View Article : Google Scholar : PubMed/NCBI
11	Wright KT, Uchida K, Bara JJ, Roberts S, El Masri W and Johnson WE: Spinal motor neurite outgrowth over glial scar inhibitors is enhanced by coculture with bone marrow stromal cells. Spine J. 14:1722–1733. 2014. View Article : Google Scholar : PubMed/NCBI
12	Sun T, Ye C, Zhang Z, Wu J and Huang H: Cotransplantation of olfactory ensheathing cells and Schwann cells combined with treadmill training promotes functional recovery in rats with contused spinal cords. Cell Transplant. 22 Suppl 1:S27–S38. 2013. View Article : Google Scholar : PubMed/NCBI
13	Tropel P, Platet N, Platel JC, Noël D, Albrieux M, Benabid AL and Berger F: Functional neuronal differentiation of bone marrow-derived mesenchymal stem cells. Stem Cells. 24:2868–2876. 2006. View Article : Google Scholar : PubMed/NCBI
14	Liu Z, He B, Zhang RY, Zhang K, Ding Y, Ruan JW, Ling EA, Wu JL and Zeng YS: Electroacupuncture promotes the differentiation of transplanted bone marrow mesenchymal stem cells pre-induced with neurotrophin-3 and retinoic acid into oligodendrocyte-like cells in demyelinated spinal cord of rats. Cell Transplant. 24:1265–1281. 2015. View Article : Google Scholar : PubMed/NCBI
15	Akiyama Y, Radtke C and Kocsis JD: Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J Neurosci. 22:6623–6630. 2002.PubMed/NCBI
16	Woodbury D, Schwarz EJ, Prockop DJ and Black IB: Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 61:364–370. 2000. View Article : Google Scholar : PubMed/NCBI
17	Barzilay R, Melamed E and Offen D: Introducing transcription factors to multipotent mesenchymal stem cells: Making transdifferentiation possible. Stem Cells. 27:2509–2515. 2009. View Article : Google Scholar : PubMed/NCBI
18	Ni WF, Yin LH, Lu J, Xu HZ, Chi YL, Wu JB and Zhang N: In vitro neural differentiation of bone marrow stromal cells induced by cocultured olfactory ensheathing cells. Neurosci Lett. 475:99–103. 2010. View Article : Google Scholar : PubMed/NCBI
19	Yui S, Fujita N, Chung CS, Morita M and Nishimura R: Olfactory ensheathing cells (OECs) degrade neurocan in injured spinal cord by secreting matrix metalloproteinase-2 in a rat contusion model. Jpn J Vet Res. 62:151–162. 2014.PubMed/NCBI
20	Ninomiya K, Iwatsuki K, Ohnishi Y, Ohkawa T and Yoshimine T: Intranasal delivery of bone marrow stromal cells to spinal cord lesions. J Neurosurg Spine. 23:111–119. 2015. View Article : Google Scholar : PubMed/NCBI
21	Torres-Espín A, Redondo-Castro E, Hernández J and Navarro X: Bone marrow mesenchymal stromal cells and olfactory ensheathing cells transplantation after spinal cord injury-a morphological and functional comparison in rats. Eur J Neurosci. 39:1704–1717. 2014. View Article : Google Scholar : PubMed/NCBI
22	Kastenmayer RJ, Moore RM, Bright AL, Torres-Cruz R and Elkins WR: Select agent and toxin regulations: Beyond the eighth edition of the guide for the care and use of laboratory animals. J Am Assoc Lab Anim Sci. 51:333–338. 2012.PubMed/NCBI
23	Nash HH, Borke RC and Anders JJ: New method of purification for establishing primary cultures of ensheathing cells from the adult olfactory bulb. Glia. 34:81–87. 2001. View Article : Google Scholar : PubMed/NCBI
24	da Silva C Balao, Macías-García B, Rodriguez A Morillo, Bolaños JM Gallardo, Tapia JA, Aparicio IM, Morrell JM, Rodriguez-Martínez H, Ortega-Ferrusola C and Peña FJ: Effect of Hoechst 33342 on stallion spermatozoa incubated in KMT or Tyrodes modified INRA96. Anim Reprod Sci. 131:165–171. 2012. View Article : Google Scholar : PubMed/NCBI
25	Sedý J, Urdzíková L, Jendelová P and Syková E: Methods for behavioral testing of spinal cord injured rats. Neurosci Biobehav Rev. 32:550–580. 2008. View Article : Google Scholar : PubMed/NCBI
26	Howard CV and Reed MG: Unbiased stereology: Three-dimensional measurement in microscopy. J Anat. 194:153–157. 1999.
27	Vawda R, Soubeyrand M, Zuccato JA and Fehlings MG: Spinal cord injury and regeneration: A critical evaluation of current and future therapeutic strategies. Pathobiol Hum Dis. 8:593–638. 2014. View Article : Google Scholar
28	Xu Y, Xiong F, Liu L and Zhang C: Rat bone marrow stromal cells could be induced into Schwann cell precursor-like cells in vitro. Neurosci Lett. 488:229–233. 2011. View Article : Google Scholar : PubMed/NCBI
29	Robey PG, Kuznetsov SA, Ren J, Klein HG, Sabatino M and Stroncek DF: Generation of clinical grade human bone marrow stromal cells for use in bone regeneration. Bone. 70:87–92. 2015. View Article : Google Scholar : PubMed/NCBI
30	Chiu LH, Lai WF, Chang SF, Wong CC, Fan CY, Fang CL and Tsai YH: The effect of type II collagen on MSC osteogenic differentiation and bone defect repair. Biomaterials. 35:2680–2691. 2014. View Article : Google Scholar : PubMed/NCBI
31	Sanchez-Ramos J, Song S, Cardozo-Pelaez F, Hazzi C, Stedeford T, Willing A, Freeman TB, Saporta S, Janssen W, Patel N, et al: Adult bone marrow stromal cells differentiate into neural cells in vitro original research article. Exp Neurol. 164:247–256. 2000. View Article : Google Scholar : PubMed/NCBI
32	Ni WF, Yin LH, Lu J, Xu HZ, Chi YL, Wu JB and Zhang N: In vitro neural differentiation of bone marrow stromal cells induced by cocultured olfactory ensheathing cells. Neurosci Lett. 475:99–103. 2010. View Article : Google Scholar : PubMed/NCBI
33	Neuhuber B, Himes B Timothy, Shumsky JS, Gallo G and Fischer I: Axon growth and recovery of function supported by human bone marrow stromal cells in the injured spinal cord exhibit donor variations. Brain Res. 1035:73–85. 2005. View Article : Google Scholar : PubMed/NCBI