The effect of bone marrow mesenchymal stem cells on recovery of skeletal muscle after neurotization surgery in rat

Document Type: Original Article

Authors

1 Neurophysiology Research Center, Department of Anatomy, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

2 Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

3 Department of Anatomy, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

4 Neurophysiology Research Center, Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

Abstract

Objective(s): When the nerve is injured near its entrance to the muscle belly, we cannot perform conventional methods. One useful method in such a situation is neurotization surgery. In this study, Bone marrow mesenchymal stem cells (BMSCs) implanted into the paralyzed muscle after neurotization surgery. These cells can stimulate axon growth and motor endplate formation, also prevent muscle atrophy.
Materials and Methods: Thirty-six adult male Sprague-Dawley rats were randomized into six groups: intact group, sham surgery group, control group, DMEM group, cell+DMEM group, denervated group. The motor nerve of the lateral head of gastrocnemius muscle was cut, and the proximal portion of the severed nerve was transplanted to the proximal third of the muscle paralysis. BMSCs with/or DMEM was injected into the site of injury. All animals were evaluated by withdrawal reflex latency (WRL), electromyography, muscle weight, histology and immunohistochemistry.
Results: The WRL difference between the control and cell+DMEM groups at weeks 4 and 12 post-operation was statistically significant (P<0.05). The mean number of motor end plates in cell+DMEM group was more than control group (P<0.05). At 12 weeks post-operation, the difference of the mean nerve conduction velocity (NCV) between cell treated group and sham surgery groups were not statistically significant (P>0.05). In weeks 4 and 12 post-operation, the mean fiber diameters in cell+DMEM group were more than control group (P<0.05).
Conclusion: The results of this study demonstrate that transplantation of BMSCs after neurotization surgery, prevent muscle atrophy and improve muscle function.

Keywords

Main Subjects


1.Bellamkonda RV. Peripheral nerve regeneration: an opinion on channels, scaffolds and anisotropy. Biomaterials 2006; 27: 3515-3518.

2.Mu L, Sobotka S, Su H. Nerve-muscle-endplate band grafting: a new technique for muscle reinnervation. Neurosurgery 2011;69: 208-224.

3.Farjah GH, HeshmatianBM, KarimipourM, SaberiA. Using eggshell membrane as nerve guide channels in peripheral nerve regeneration. Iran J

Basic Med Sci 2013;16: 901-905.

4.Wehbe J, Chidiac R, Maalouf G. Neurotization by adjacent muscle. Pan Arab J Orth Trauma 2004; 8: 69-76.

5.Bielecki M, Skowronski R, Skowronski J. A comparative morphological study of direct nerve implantation and neuromuscular pedicle methods in cross reinnervation of the rat skeletal muscle. Rocz Akad Med Bialymst 2004; 49: 10-17.

6.Noordin S, Ahmed M, Rehman R, Ahmad T, Hashmi P. Neuronal regeneration in denervated muscle following sensory and muscular neurotization. Acta Orthop 2008;79:126-133.

7.Ritfeld GJ, Nandoe Tewarie RD, Vajn K, Rahiem ST, Hurtado A, Wendell DF, et al. Bone marrow stromal cell-mediated tissue sparing enhances functional repair after spinal cord contusion in adult rats. Cell Transplant 2012; 21: 1561-1575.

8.Pereira Lopes FR, Camargo de Moura Campos L, Dias Correa RJ Jr, Balduino A, Lora S, Langone F. Bone marrow stromal cells and resorbable collagen guidance tubes enhance sciatic nerve regeneration in mice. Exp Neurol 2006;198:457-468.

9.Bhagavati S, Xu W. Isolation and enrichment of skeletal muscle progenitor cells from mouse bone marrow. Biochem Biophys Res Commun 2004; 318: 119-124.

10.Horwitz E, Le Blanc K, Dominici M, Mueller I, Slaper-Cortenbach I, Marini FC, et al. Clarification of the nomenclature for MSC: The International Society for Cellular Therapy position statement. Cytotherapy 2005;7:393-395.

11.Cantinieaux, D, Quertainmont R, Blacher S, Rossi L, Wanet T, Noël A, et al. Conditioned medium from bone marrow-derived mesenchymal stem cells improves recovery after spinal cord injury in rats: an original strategy to avoid cell transplantation. PloS One 2013; 8: e69515.

12. Dezawa, M, Kanno H, Hoshino M, Cho H, Matsumoto N, Itokazu Y, et al. Specific induction of neuronal cells from bone marrow stromal cells and application for autologous transplantation. J Clin Invest 2004; 113: 1701-1710.

13.Dadon-Nachum M, Melamed E, Offen D. Stem cells treatment for sciatic nerve injury. Expert OpinBiolTher 2004; 11: 1591-1597.

14.Parr AM, Tator CH, Keating A. Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury. Bone Marrow Transplant 2007; 40: 609-619.

15.Zarbakhsh S, Bakhtiyari M, Faghihi A, Joghataei MT, Mehdizadeh M, Khoei S, et al. The Effects of Schwann and bone marrow stromal stem cells on sciatic nerve injury in rat: A comparison of functional recovery. Cell J 2012;14:39-46.

16.Fukuda A, Hirata H, Akeda K, Morita A, Nagakura T. Tsujii M. Enhanced reinnervation after neurotization with Schwann cell transplantation. Muscle Nerve 2005; 31: 229-234.

17.Konya D, Liao WL, Choi H, Yu D, Woodard MC, Newton KM, et al. Functional recovery in T13-L1 hemisected rats resulting from peripheral nerve rerouting: role of central neuroplasticity. Regen Med 2008; 3: 309-327.

18.Farjah GH, Fazli F. The effect of chick embryo amniotic fluid on sciatic nerve regeneration of rats. Iran J Vet Res 2015;16:167-171.

19.Azizi S, Mohammadi R, Amini K, Fallah R, Karegar K. Bridging small-gap peripheral nerve defect using silicone rubber chamber in the rat sciatic nerve transection model. Vet Res Forum 2012;1:107-115.

20.Isaacs J, Feher J, Shall M, Vota S, Fox MS, Mallu S, et al. Spita Effects of nandrolone on recovery after neurotization of chronically denervated muscle in a rat model. J Neurosurg 2013; 119: 914-923.

21.Chen J, Li Y, Wang L, Zhang Z, Lu D, Lu M, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 2001; 32: 1005-1011.

22.Uchida N, Fujita A, Hsieh MM, Bonifacino A, Krouse AE, Metzger ME, et al. Bone marrow as a hematopoietic stem cell source for gene therapy in sickle cell disease (SCD): evidence from rhesus and SCD patients. Hum Gene Ther Clin Dev 2017; doi: 10.1089/humc.2017.029

23.Prockop D. Heritable osteoarthritis. Diagnosis and possible modes of cell and gene therapy. Osteoarthritis Cartilage 1999;7:364-366.

24.Urdzíková L, Jendelová P, Glogarová K, Burian M, Hájek M, Syková E. Transplantation of bone marrow stem cells as well as mobilization by granulocyte-colony stimulating factor promotes recovery after spinal cord injury in rats. J Neurotrauma 2006;23:1379-1391.

25.Chopp M, Zhang XH, Li Y, Wang L, Chen J, Lu D, et al. Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation. Neuroreport 2000;11:3001-3005.

26.He J, Teng X, Yu Y, Huang H, Ye W, Ding Y, et al. Injection of Sca-1+/CD45+/CD31+ mouse bone mesenchymal stromal-like cells improves cardiac function in a mouse myocardial infarct model. Differentiation 2013; 86:57-64.

27.Vogel G. Can old cells learn new tricks?. Science 2000; 287:1418-9.

28.Ozdal-kurt F, Tuglu I, Vatsnsever HS, Tong S, Sen BH, Deliloglu-Gurhan SI. The effect of different implant biomaterials on the behavior of canine bone marrow stromal cells during their differentiation into osteoblasts. Biotech Histochem 2016; 91:412-422.

29.Lee B, Han L, Frank EH, Grodzinsky AJ, Ortiz C. Dynamic nanomechanics of individual bone marrow stromal cells and cell-matrix composites during chondrogenic. J Biomech. 2015; 48:171-175.

30.Lu J, Moochhala S, Moore XL, Ng KC, Tan MH, Lee LK, et al. Adult bone marrow cells differentiate into neural phenotypes and improve functional recovery in rats following traumatic brain injury. Neurosci Lett 2006; 398:12-17.

31.Inoue M, Honmou O, Oka S, Houkin K, Hashi K, Kocsis JD. Comparative analysis of remyelinating potential of focal and intravenous administration of autologous bone marrow cells into the rat demyelinated spinal cord. Glia 2003;44:111-118.

32.Vathana T, Nijhuis TH, Friedrich PF, Bishop AT, Shin AY. An experimental study to determine and correlate choline acetyltransferase assay with functional muscle testing after nerve injury. J Neurosurg 2014; 120:1125-1130.

33.Dow DE, Carlson BM, Hassett CA, Dennis RG, Faulkner JA. Electrical stimulation of denervated muscles of rats maintains mass and force, but not recovery following grafting. Restor Neurol Neurosci 2006; 24:41-54.

34.Zhen G, Xue Z, Zhao J, Gu N, Tang Z, Xu, et al. Mesenchymal stem cell transplantation increases expression of vascular endothelial growth factor in papain-induced emphysematous lungs and inhibits apoptosis of lung cells. Cytotherapy 2010; 12: 605-614.

35.Delk NA, Farach-Carson MC. Interleukin-6: a bone marrow stromal cell paracrine signal that induces neuroendocrine differentiation and modulates autophagy in bone metastatic PCa cells. Autophagy 2012; 8:650-663.

36.Björklund LM, Sánchez-Pernaute R, Chung S, Andersson T, Chen IYC, McNaught KSP, et al. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA 2002;99:2344-2349.

37.Mahmood A, Lu D, Wang L, Chopp M. Intracerebral transplantation of marrow stromal cells cultured with neurotrophic factors promotes functional recovery in adult rats subjected to traumatic brain injury. J Neurotrauma 2002;19:1609-1617.

38.Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neuroscie Res 2000;61:364-370.

39.Jendelová P, Herynek V, Urdzikova L, Glogarová K, Kroupová J, Andersson B, et al. Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord. J Neurosci Res 2004; 76:232-243.

40.Di Nicola M, Carlo-Stella C, Magni M, Milanesi M, Longoni PD, Matteucci P, et al. Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli. Blood 2002;99:3838-3843.

41.Kolf CM, Cho E, Tuan RS. Mesenchymal stromal cells: biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation. Arthritis Res Ther 2007;9:1-10.

42.Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 1999;96:10711-10716.

43.Hocking AM, Gibran NS. Mesenchymal stem cells: paracrine signaling and differentiation during cutaneous wound repair. Exp Cell Res 2010;316:2213-2219.

44.Lee EY, Xia Y, Kim WS, Kim MH, Kim TH, Kim KJ, et al. Hypoxia‐enhanced wound‐healing function of adipose‐derived stem cells: Increase in stem cell proliferation and up‐regulation of VEGF and bFGF. Wound Repair Regen 2009;17:540-547.

45.Smith AN, Willis E, Chan VT, Muffley LA, Isik FF, Gibran NS, et al. Mesenchymal stem cells induce dermal fibroblast responses to injury. Exp Cell Res 2010;316:48-54.

46.Brunelli G, Monini L. Direct muscular neurotization. J hand Surg 1985;10:993-997.

47.Chiu DT, Chen L, Spielholtz N, Beasley R. A comparative electrophysiological study on neurotisation in rats. J Hand Surg Br 1991;16:505-510.

48.Li Y, Choppm M, Chen J, Wang L, Gautam SC, Xu YX, et al. Interstriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab 2000; 20:1311-1319.

49.Song S, Kamath S, Mosquera D, Zigova T, Sanberg P, Vesely D, et al. Expression of brain natriuretic peptide by human bone marrow stromal cells. Exp Neurol 2004;185:191-197.

50.Chen CJ, Ou YC, Liao SL, Chen WY, Chen SY, Wu CW, et al. Transplantation of bone marrow stromal cells for peripheral nerve repair. Exp Neurol 2007;204:443-453.

51.Wakao S, Hayashi T, Kitada M, Kohama M, Matsue D, Teramoto N, et al. Long-term observation of auto-cell transplantation in non-human primate reveals safety and efficiency of bone marrow stromal cell-derived Schwann cells in peripheral nerve regeneration. Exp Neurol 2010;223:537-547.

52.Kang SB, Olson JL, Atala A, Yoo JJ. Functional recovery of completely denervated muscle: implications for innervation of tissue-engineered muscle. Tissue Eng Part A 2012;18:1912-1920.

53.Watson JA, Bahattacharyya BJ, Vaden JH, Wilson JA, Icyuz M, Howard AD, et al. Motor and sensory deficits in the teetering mice result from mutation of the ESCRT component HGS. PLoS Genet 2015; 26:11:e 1005290.

54.Virtanen P, Tolonen U, Savolainen J, Takala T. Effect of reinnervation on collagen synthesis in rat skeletal muscle. J Appl Physiol 1992;72:2069-2074.

55.Manganelli F, Pisciotta C, Reilly MM, Tozza S, Schenone A, Fabrizi GM, et al. Nerve conduction velocity in CMT1A: what else can we tell?. Eur J Neurol 2016; 23:1566-1571.