Current issue
Archive
About the Journal
About us
Aims and Scope
Indexing and Abstracting
Editorial Office
Open Access Policy
Publication Ethics
Contact
For Authors
Editorial Policy
Peer Review Policy
Manuscript Preparation Guidelines
Copyright & Licensing
Publication Fees
Fast-Track Paper Publication Option
Conflict Interest Guidance
Submit an Article
Special Issues
News & Editorials
“Fake,” “Predatory,” and “Pseudo” Journals: Charlatans Threatening Trust in Science
Shifting the Journal submission-review system to the Editorial System Manuscript December 27, 2017.
ORIGINAL ARTICLE
The effect of human umbilical cord-derived mesenchymal stem cell conditioned medium on the peripheral nerve regeneration of injured rats
1
Department of Anatomy, Faculty of Medicine, Universitas Indonesia, Indonesia
2
Department of Neurosurgery, Faculty of Medicine, Universitas Indonesia, Dr. Cipto Mangunkusumo General Hospital/Faculty of Medicine Universitas Indonesia, Indonesia
3
Departemen Histology, Faculty of Medicine, Universitas Indonesia, Indonesia
4
Stem Cell Medical Technology Integrated Service Unit, Dr. Cipto Mangunkusumo General Hospital/Faculty of Medicine Universitas Indonesia, Indonesia
5
Stem Cell and Tissue Engineering Research Center, Indonesia Medical Education and Research Institute (IMERI), Faculty of Medicine Universitas Indonesia, Indonesia
6
Department of Physiology, Faculty of Medicine, Universitas Indonesia, Indonesia
7
Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Indonesia
Online publication date: 2019-12-18
Publication date: 2019-12-18
Electron J Gen Med 2019;16(6):em171
KEYWORDS
ABSTRACT
Peripheral nerve injury occurs in 3-10% of extremity trauma patients. Mesenchymal stem cells (MSCs) have been used in injuries. Nevertheless, the mechanism of human umbilical cord MSCs (UC-MSCs) and/or their conditioned medium (CM) capacity in regenerating peripheral nerves is not widely known. This study is aimed to determine the mechanism, of UC-MSC CM in improving the structure and function of the nerves after peripheral nerve injury. This experimental study used Sprague-Dawley rats. The experimental animals were divided into 3 groups: control (Sham [SH]), and treatment groups (standard therapy [ST] and CM). The sciatic nerve of the SH group was not injured (only exposed and closed), while those of the ST and CM groups were both cut and given standard sutures. The CM group was treated with topical UC-MSCs CM. The study was divided into two stages i.e. a short-term and long-term research to check the parameters at 7 and 70 days post injury (dPI), respectively. The parameters collected were motor functions (walking analysis), electrophysiology and structural parameters. There were signs of nerve injury in all rats on 3 dPI. CM group showed faster recovery on 14 dPI compared with the ST group that only showed improvement after the 28th dPI. Electrophysiological images showed better electrical conduction in CM than ST group, while histological features showed higher S100 marker was expressed in CM compared with ST, as well as SH group on 7 and 70 dPI. Overall, UC-MSC CM affected peripheral nerve regeneration after 14 dPI.
REFERENCES (62)
1.
Aguilar V, Fajas L. Cycling through metabolism. EMBO Molecular Medicine, 2010:338-48. https://doi.org/10.1002/emmm.2... PMid:20721988 PMCid:PMC3118222.
2.
Akassoglou K, Yu WM, Akpinar P, Strickland S. Fibrin inhibits peripheral nerve remyelination by regulating schwann cell differentiation. Cell Press, 2002;33:861-75. https://doi.org/10.1016/s0896-....
3.
Allodi I, Udina E, Navarro X. Specificity of peripheral nerve regeneration: interactions at the axon level. Progress in Neurobiology, 2012;98:16-37. https://doi.org/10.1016/j.pneu... PMid:22609046.
4.
Amniattalab A, Mohammadi R. Functional, histopathological and immunohistichemical assessments of cyclosporine a on sciatic nerve regeneration using allografts: a rat sciatic nerve model. Bulletin of Emergency and Trauma, 2017;5(3);152-59. PMID:28795058.
5.
Asano F. A novel gait generation method independent of target settling-time adjustment for underactuated limit cycle walking. Multibody System Dynamics, 2015;37(2):227-44. https://doi.org/10.1007/s11044....
6.
Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of complete sciatic peroneal and posterior tibial nerve lesions in the rat. Plastic and Reconstructive Surgery, 1987:129-36. https://doi.org/10.1097/000065... PMid:2909054.
7.
Cattin AL, Lloyd AC. The multicellular complexity of peripheral nerve regeneration. Current Opinion in Neurobiology, 2016;39:38-46. https://doi.org/10.1016/j.conb... PMid:27128880.
8.
Chen TY, Yang YC, Sha YN, Chou JR, Liu BS. Far-infrared therapy promotes nerve repair following end-to-end neurorrhapy in rat models of sciatic nerve injury. Hindawi Publishing Corporation, 2015;1-10. https://doi.org/10.1155/2015/2... PMid:25722734 PMCid:PMC4333284.
9.
Chhabra A, Ahlawat S, Belzberg A, Andreseik G. Peripheral nerve injury grading simplified on MR neurography: As referenced to Seddon and Sunderland classifications. Indian Journal of Radiology and Imaging, 2014;24(3):217-24. https://doi.org/10.4103/0971-3... PMid:25114384 PMCid:PMC4126136.
10.
Drake RL, Vogl AW, Mitchell AWM. Gray’s anatomy for students flash cards. 3rd ed. Churchill Livingstone Elsevier Inc, Philadelphia. 2015:391.
11.
Fletcher A. Action potential: generation and propagation. Anasesthesia and Intensive Care Medicine, 2008;9(6):251-55. https://doi.org/https://doi.or....
12.
Fu SY, Gordon T. The cellular and molecular basis of peripheral nerve regeneration. Molecular Neurobiology, 1997;14:67-116. https://doi.org/10.1007/BF0274... PMid:9170101.
13.
Gao X, Wang Y, Chen J, Peng J. The role of peripheral nerve ECM components in the tissue engineering nerve construction. Rev. Neurosci, 2013;24(4):443-53. https://doi.org/10.1515/revneu....
14.
Gasparini ALP, Barbieri CH, Mazzer N. Correlation between different methods of gait functional evaluation in rats with ischiatic nerve crushing injuries. ACTA ORTHOP BRAS, 2007;15(5):285-89. https://doi.org/10.1590/S1413-....
15.
George ML, Tutton MG, Janssen F, Arnaout A, Abulafi AM, Eccles SA. VEGF-A, VEGF-C and VEGF-D in colorectal cancer progression. Neoplasia, 2001;3(5):420-7. https://doi.org/10.1038/sj.neo... PMID:11687953 PMCid:PMC1506210.
16.
Goss JR, Goins WF, Lacomis D, Mata M, Glorioso JC, Fink DJ. Herpes simplex-mediated gene transfer of nerve growth factor protects against peripheral neuropathy in streptozotocin-induced diabetes in the mouse. Diabetes, 2002;51:2227-32. https://doi.org/10.2337/diabet... PMid:12086954.
18.
Gustafson KJ, Grinberg Y, Joseph S, Triolo RJ. Human distal sciatic nerve fascicular anatomy: implication for ankle control using nerve-cuff electrodes. JRRD, 2012;49(2):309-22. https://doi.org/10.1682/JRRD.2... PMID:22773531.
19.
Hargus NJ, Patel MK. Voltage-gated Na+ channels in neuropathic pain. Expert opinion, 2007;16(5): 635-46. https://doi.org/10.1517/135437... PMid:17461737.
20.
Hellweg R, Hartung H. Rapid Communication: Endogenous levels of nerve growth factor (NGF) are altered in experimental diabetes mellitus: a possible role for NGF in the pathogenesis of diabetic neuropathy. Journal of Neuroscience Research, 1990;26:258-67. https://doi.org/10.1002/jnr.49... PMid:2142224.
21.
Hobson MI, Green CJ, Terenghi G. VEGF enhances intraneural angiogenesis and improves nerve regeneration after axotomy. J. Anat, 2000;197(4):591-605. https://doi.org/10.1046/j.1469... PMid:11197533 PMCid:PMC1468175.
22.
Huebner EA, Strittmatter SM. Axon regeneration in the peripheral and central nervous systems. Results Probl Cell Differ., 2009;48:339-51. https://doi.org/10.1007/400_20... PMid:19582408 PMCid:PMC2846285.
23.
Inda AM, García MN, Andrini LB, Garcia AL, Blanco AF, Furnus CC, et al. Evaluation of Angiogenesis with the Expression of VEGF-C and CD34 in Human Colon Cancer. Current Chemical Biology, 2009;3:302-5. https://doi.org/10.2174/221279....
24.
Jiang L, Jones S, Jia X. Stem cell transplantation for peripheral nerve regeneration: current options and opportunities. International Journal of Molecular Science, 2017;18(94):1-17. https://doi.org/10.3390/ijms18... PMid:28067783 PMCid:PMC5297728.
25.
Johnson EO, Zoubos AB, Soucacos PN. Regeneration and repair of peripheral nerves. Injury Int J Care Injured., 2005;36(4):24-9. https://doi.org/10.1016/j.inju... PMid:16288757.
26.
Kern S, Eichler H, Stoeve J, Kluter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells, 2006;(24):1294-301. https://doi.org/10.1634/stemce... PMid:16410387.
27.
Kolch W. Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem J, 2000;351:289-305. https://doi.org/10.1042/bj3510... PMID:11023813 PMCid:PMC1221363.
28.
Kuroda Y, Kitada M, Wakao S, Dezawa M. Mesenchymal stem cells and umbilical cord as sources for schwann cell differentiation: their potential in peripheral nerve repair. The Open Tissue Engineering and Regenerative Medicine Journal, 2011;4:54-63. https://doi.org/10.2174/187504....
29.
Lundborg G. A 25-year perspective of peripheral nerve surgery: evolving neuroscientific concepts and clinical significance. The Journal of Hand Surgery, 2000:391-414. https://doi.org/10.1053/jhsu.2... PMid:10811744.
30.
Lutz M, Rosenberg M, Kiessling F, Eckstein V, Heger T, Krebs J, et al. Local injection of stem cell factor (SCF) improves myocardial homing of systemically delivered c-kit + bone marrow-derived stem cells. Cardiovascular Research, 2008;77:143-50. https://doi.org/10.1093/cvr/cv... PMid:18006465.
31.
Margiana R, Jusuf AA, Aman RA, Liem IK, Pawitan JA. A new method in walking analysis using the angles around the midpoint between print length and toe spread by four different color footprints. IJSBAR, 2015;21(1):117-28. Available at: https://pdfs.semanticscholar.o....
32.
Marieb EN, Hoehn K. Human anatomy & Physiology. 9th Ed. Pearson Education, Inc. United Stated. 2013:1107.
33.
Martins RS, Bastos D, Siqueira MG, Heise COC, Teixeira MJ. Traumatic injuries of peripheral nerves: a review with emphasis on surgical indication. Arq Neuropsiquiatr, 2013;71(10):811-4. https://doi.org/10.1590/000428... PMid:24212521.
34.
Matsuse D, Kitada M, Kohama M, Nishikawa K, Makinoshima H, Wakao S, et al. Human umbilical cord-derived mesenchymal stromal cells differentiate into functional schwann cells that sustain peripheral nerve regeneration. J Neuropathol Exp Neurol, 2010;69(9):973-85. https://doi.org/10.1097/NEN.0b... PMid:20720501.
35.
Medinaceli LD, Freed WJ, Wyatt RJ. An index of the functional condition of rat sciatic nerve based on measurements made from walking tracks. Experimental Neurology, 1982;77:634-43. https://doi.org/10.1016/0014-4....
36.
Menorca RMG, Fussell TS, Elfar JC. Nerve physiology mechanism of injury and recovery. Hand Clin, 2013;29:317-30. https://doi.org/10.1016/j.hcl.... PMid:23895713 PMCid:PMC4408553.
37.
Mohammadi R, Ahsan S, Masoumi M, Amini K. Vascular endhothelial growth factor promotes peripheral nerve generation after sciatic nerve transection in rat. Chinese Journal of Traumatology, 2013;16(6):323-29. PMID: 24295576.
38.
Monte-Raso VV, Barbieri CH, Mazzer N, Yamasita AC, Barbieri G. Is the sciatic functional index always reable and reproducible?. Journal of Neuroscience methods, 2008;170:255-61. https://doi.org/10.1016/j.jneu... PMid:18325595.
39.
Navarro X, Udina E. Methods and protocols in peripheral nerve regeneratiexperimental research: part iii – electrophysiological evaluation. International Review of Neurobiology, 2009;87:105-26. https://doi.org/10.1016/S0074-....
40.
Pawitan JA, Liem IK, Budiyanti E, Fasha I, Feroniasanti L, Jamaan T, et al. Umbilical cord derived stem cell culture: multiple-harvest explant method. International Journal of PharmTech Research, 2014;6(4):1202-1208. Available at: https://www.researchgate.net/p....
41.
Pawitan JA, Wulandari D, Suryani D, Damayanti L, Liem IK. Comparison of flowcytometric immunocytochemistry analysis of stem cell surface markers. Journal of Biological Science, 2015;15(1):1-5. https://doi.org/10.3844/ojbsci....
42.
Pawitan JA, Leviana M, Sukmawati D, Liem IK, Margiana R, Tarcisia T. Prospect of umbilical cord mesenchymal stem cell culture wastein regenerative medicine. Journal of Global Pharma Technology, 2017: 1-5. Available at: https://scholar.ui.ac.id/en/pu....
43.
Pereira WC, Khushnooma I, Madkaikar M, Ghosh K. Reproducible methodology for the isolation of mesenchymal stem cells from human umbilical cord and its potential for cardiomyocyte generation. Journal of Tissue Engineering and Regenerative Medicine, 2008;2:394-9. https://doi.org/10.1002/term.1... PMid:18615777.
44.
Pfister LA, Papaloizos M, Merkle HP, Gander B. Nerve conduits and growth factor delivery in peripheral nerve repair. Journal of the Peripheral Nervous System, 2007;12:65-82. https://doi.org/10.1111/j.1529... PMid:17565531.
45.
Pola R, Aprahamian TR, Bosch-Marce M, Curry C, Gaetani E, Flex A, et al. Age-dependent VEGF expression and intraneural neovascularization during regeneration of peripheral nerves. Neurobiology of Aging, 2004;25:1361-68. https://doi.org/10.1016/j.neur... PMid:15465634.
46.
Pons J, et al. VEGF improves survival of mesenchymal stem cells in infarcted hearts. Biochemical and Biophysical Research Communications, 2007;376(2):419-22. https://doi.org/10.1016/j.bbrc... PMid:18789891.
47.
Rosberg HE, Carlsson KS, Cederlund RI, Ramel E, Dahlin LB. Costs and outcome for serious hand and arm injuries during the first year after trauma - a prospective study. BMC Public Health, 2013;(13):501:1-7. https://doi.org/10.1186/1471-2... PMid:23706070 PMCid:PMC3681586.
48.
Rubin DI, Hermann RC. Chapter 105: Peripheral nerve injury. Neurology and Clinical Neuroscience, Philadelphia. 2007:1410-22. https://doi.org/10.1016/B978-0....
49.
Schulz A, Walther C, Morrison H, Bauer R. In vivo electrophysiological measurements on mouse sciatic nerves. Journal of Visualized Experiments, 2014;86(51181):1-8. https://doi.org/10.3791/51181 PMCid:PMC4166965.
50.
Seddon HJ. A classification of nerve injuries. British Medical Journal, 1942:237-39. https://doi.org/10.1136/bmj.2.... PMid:20784403 PMCid:PMC2164137.
51.
Siemionow M, Bozkurt M, Zor F. Regeneration and repair of peripheral nerves with different biomaterials: review. Microsurgery, 2010;30(7): 575-88. https://doi.org/10.1002/micr.2... PMid:20878689.
52.
Silva DN, Coelho J, Frazilio FO, Odashiro AN, Carvalho PTC, Pontes ERJC, Vargas AF, Rosseto M, Silva ABA. End-to-side nerve repair using fibrin glue in rats. Experimental Neurology, 2010;25(2):158-62. https://doi.org/10.1590/S0102-... PMid:20305882.
53.
Svennigsen AF, Dahlin LB. Review: Repair of the peripheral nerve—remyelination that works. Brain Sciences, 2013;3:1182-97. https://doi.org/10.3390/brains... PMid:24961524 PMCid:PMC4061866.
54.
Tikoo R, Zanazzi G, Shiffman D, Salzer J, Chao MV. Cell cycle control of schwann cell proliferation: Role of cyclin-dependent kinase-2. The Journal of Neuroscience, 2000;20(12):4627-34. https://doi.org/10.1523/JNEURO... PMid:10844032 PMCid:PMC6772447.
55.
Tortora GJ, Derrickson B. Principles of anatomy & physiology. 14th ed. John Wiley & Sons, Inc. Hoboken. 2014: 1089.
56.
Varejao ASP, Cabrita AM, Patricio JA, Bulas-Cruz J, Gabriel RC, Melo-Pinto P, et al. Functional assessment of peripheral nerve recovery in the rat: Gait Kinematics. Microsurgery, 2001;21:383-88. https://doi.org/10.1002/micr.2... PMID:11757066.
57.
Varejao ASP, Cabrita AM, Geuna S, Melo-Pinto P, Filipe VM, Gramsbergen A, et al. Toe out angle: a functional index for the evaluation of sciatic nerve recovery in the rat model. Experimental Neurology, 2003;183:695-99. https://doi.org/10.1016/S0014-....
58.
Volarevic V, Arsenijevic N, Lukic ML, Stojkovic M. Concise review: Mesenchymal stem cell treatment of the complications of diabetes mellitus. Stem Cells, 2011;29(1):5-10. https://doi.org/10.1002/stem.5... PMid:21280154 PMCid:PMC3059410.
59.
Zarbakhsh S, Goudarzi N, Shirmohammadi M, Safari M. Histological study of bone marrow and umbilical cord stromal cell transplantation in regenerating rat peripheral nerve. Cell J, 2016;17(4):668-77. https://doi.org/10.22074/cellj....
60.
Zacharek A, Chen J, Li A, Cui X, Li Y, Roberts C, Feng Y, Gao Q, Chopp M. Angiopoietin1/TIE2 and VEGF/FLK1 Induced by MSC Treatment Amplifies Angiogenesis and Vascular Stabilization after Stroke, 2007;27(10):1684-91. https://doi.org/10.1038/sj.jcb... PMid:17356562 PMCid:PMC2796470.
61.
Zhang P, Xue F, Zhao F, Lu H, Zhang H, Jiang B. The immunohistological observation of proliferation rule of schwann cell after sciatic nerve injury in rats. Artificial Cells, Blood Substitutes, and Biotechnology, 2008;36:150-55. https://doi.org/10.1080/107311... PMid:18437591.
62.
Zuo J, Neubauer D, Graham J, Krekoski CA, Ferguson TA, Muir D. Regeneration of axons after nerve transection repair is enhanced by degradation of chondroitin sulfate proteoglycan. Exp Neurol, 2002;176:221-28. https://doi.org/10.1006/exnr.2... PMid:12093099.
| eISSN: | 2516-3507 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
