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Pereira, T.; Gärtner, A.; Amorim, I.; Almeida, A.; Caseiro, A. R.; Armada-da-Silva, Paulo A. S.; Amado, Sandra; Fregnan, Federica; Varejão, A. S. P.; Santos, J. D.; Bartolo, P. J.; Geuna, S.; Luís, A. L.; Mauricio, A. C. (2014)
Publisher: Hindawi Publishing Corporation
Journal: BioMed Research International
Languages: English
Types: Article
Subjects: R, Research Article, Medicine, Article Subject
In peripheral nerves MSCs can modulate Wallerian degeneration and the overall regenerative response by acting through paracrine mechanisms directly on regenerating axons or upon the nerve-supporting Schwann cells. In the present study, the effect of human MSCs from Wharton's jelly (HMSCs), differentiated into neuroglial-like cells associated to poly (DL-lactide-ε-caprolactone) membrane, on nerve regeneration, was evaluated in the neurotmesis injury rat sciatic nerve model. Results in vitro showed successful differentiation of HMSCs into neuroglial-like cells, characterized by expression of specific neuroglial markers confirmed by immunocytochemistry and by RT-PCR and qPCR targeting specific genes expressed. In vivo testing evaluated during the healing period of 20 weeks, showed no evident positive effect of HMSCs or neuroglial-like cell enrichment at the sciatic nerve repair site on most of the functional and nerve morphometric predictors of nerve regeneration although the nociception function was almost normal. EPT on the other hand, recovered significantly better after HMSCs enriched membrane employment, to values of residual functional impairment compared to other treated groups. When the neurotmesis injury can be surgically reconstructed with an end-to-end suture or by grafting, the addition of a PLC membrane associated with HMSCs seems to bring significant advantage, especially concerning the motor function recovery.
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    • Keilhoff, G., Fansa, H.. Mesenchymal stem cells for peripheral nerve regeneration—a real hope or just an empty promise?. Experimental Neurology. 2011; 232 (2): 110-113
    • Siemionow, M., Bozkurt, M., Zor, F.. Regeneration and repair of peripheral nerves with different biomaterials: review. Microsurgery. 2010; 30 (7): 574-588
    • Geuna, S., Papalia, I., Tos, P.. End-to-side (terminolateral) nerve regeneration: a challenge for neuroscientists coming from an intriguing nerve repair concept. Brain Research Reviews. 2006; 52 (2): 381-388
    • Stoll, G., Griffin, J. W., Li, C. Y., Trapp, B. D.. Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation. Journal of Neurocytology. 1989; 18 (5): 671-683
    • Mackinnon, S. E., Doolabh, V. B., Novak, C. B., Trulock, E. P.. Clinical outcome following nerve allograft transplantation. Plastic and Reconstructive Surgery. 2001; 107 (6): 1419-1429
    • Pereira, J. E., Cabrita, A. M., Filipe, V. M., Bulas-Cruz, J., Couto, P. A., Melo-Pinto, P., Costa, L. M., Geuna, S., Maurício, A. C., Varejão, A. S. P.. A comparison analysis of hindlimb kinematics during overground and treadmill locomotion in rats. Behavioural Brain Research. 2006; 172 (2): 212-218
    • Bongso, A., Fong, C.-Y., Gauthaman, K.. Taking stem cells to the clinic: major challenges. Journal of Cellular Biochemistry. 2008; 105 (6): 1352-1360
    • Dominici, M., le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F. C., Krause, D. S., Deans, R. J., Keating, A., Prockop, D. J., Horwitz, E. M.. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8 (4): 315-317
    • Tögel, F., Weiss, K., Yang, Y., Hu, Z., Zhang, P., Westenfelder, C.. Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. American Journal of Physiology—Renal Physiology. 2007; 292 (5): F1626-F1635
    • Zhang, M., Mal, N., Kiedrowski, M., Chacko, M., Askari, A. T., Popovic, Z. B., Koc, O. N., Penn, M. S.. SDF-1 expression by mesenchymal stem cells results in trophic support of cardiac myocytes after myocardial infarction. The FASEB Journal. 2007; 21 (12): 3197-3207
    • Dimmeler, S., Burchfield, J., Zeiher, A. M.. Cell-based therapy of myocardial infarction. Arteriosclerosis, Thrombosis, and Vascular Biology. 2008; 28 (2): 208-216
    • Gärtner, A., Pereira, T., Armada-da-Silva, P., Amado, S., Veloso, A., Amorim, I., Ribeiro, J., Bárcia, R., Cruz, P.. Effects of umbilical cord tissue mesenchymal stem cells (UCX) on rat sciatic nerve regeneration after neurotmesis injuries. Journal of Stem Cells & Regenerative Medicine. 2014; 10 (1)
    • Fu, Y.-S., Cheng, Y.-C., Lin, M.-Y. A., Cheng, H., Chu, P.-M., Chou, S.-C., Shih, Y.-H., Ko, M.-H., Sung, M.-S.. Conversion of human umbilical cord mesenchymal stem cells in Wharton's Jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells. 2006; 24 (1): 115-124
    • Mitchell, K. E., Weiss, M. L., Mitchell, B. M., Martin, P., Davis, D., Morales, L., Helwig, B., Beerenstrauch, M., Abou-Easa, K., Hildreth, T., Troyer, D.. Matrix cells from Wharton's jelly form neurons and glia. Stem Cells. 2003; 21 (1): 50-60
    • Sarugaser, R., Lickorish, D., Baksh, D., Hosseini, M. M., Davies, J. E.. Human umbilical cord perivascular (HUCPV) cells: a source of mesenchymal progenitors. Stem Cells. 2005; 23 (2): 220-229
    • Wang, J.-F., Wang, L.-J., Wu, Y.-F., Xiang, Y., Xie, C.-G., Jia, B.-B., Harrington, J., McNiece, I. K.. Mesenchymal stem/progenitor cells in human umbilical cord blood as support for ex vivo expansion of CD34+ hematopoietic stem cells and for chondrogenic differentiation. Haematologica. 2004; 89 (7): 837-844
    • Weiss, M. L., Medicetty, S., Bledsoe, A. R., Rachakatla, R. S., Choi, M., Merchav, S., Luo, Y., Rao, M. S., Velagaleti, G., Troyer, D.. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson's disease. Stem Cells. 2006; 24 (3): 781-792
    • Weiss, M. L., Mitchell, K. E., Hix, J. E., Medicetty, S., El-Zarkouny, S. Z., Grieger, D., Troyer, D. L.. Transplantation of porcine umbilical cord matrix cells into the rat brain. Experimental Neurology. 2003; 182 (2): 288-299
    • Gärtner, A., Pereira, T., Armada-da-Silva, P. A. S., Amorim, I., Gomes, R., Ribeiro, J., França, M. L., Lopes, C., Porto, B., Sousa, R., Bombaci, A., Ronchi, G., Fregnan, F., Varejão, A. S. P., Luís, A. L., Geuna, S., Maurício, A. C.. Use of poly(DL-lactide-ε-caprolactone) membranes and mesenchymal stem cells from the Wharton's jelly of the umbilical cord for promoting nerve regeneration in axonotmesis: in vitro and in vivo analysis. Differentiation. 2012; 84 (5): 355-365
    • Meek, M. F., Coert, J. H.. Clinical use of nerve conduits in peripheral-nerve repair: review of the literature. Journal of Reconstructive Microsurgery. 2002; 18 (2): 97-109
    • Luís, A. L., Rodrigues, J. M., Geuna, S., Amado, S., Shirosaki, Y., Lee, J. M., Fregnan, F., Lopes, M. A., Veloso, A. P., Ferreira, A. J., Santos, J. D., Armada-Da-Silva, P. A. S., Varejão, A. S. P., Maurício, A. C.. Use of PLGA 90:10 scaffolds enriched with in vitro-differentiated neural cells for repairing rat sciatic nerve defects. Tissue Engineering A. 2008; 14 (6): 979-993
    • Luis, A. L., Rodrigues, J. M., Amado, S., Veloso, A. P., Armada-Da-Silva, P. A. S., Raimondo, S., Fregnan, F., Ferreira, A. J., Lopes, M. A., Santos, J. D., Geuna, S., Varejão, A. S. P., Maurício, A. C.. PLGA 90/10 and caprolactone biodegradable nerve guides for the reconstruction of the rat sciatic nerve. Microsurgery. 2007; 27 (2): 125-137
    • Luís, A. L., Rodrigues, J. M., Geuna, S., Amado, S., Simões, M. J., Fregnan, F., Ferreira, A. J., Veloso, A. P., Armada-Da-Silva, P. A. S., Varejão, A. S. P., Maurício, A. C.. Neural cell transplantation effects on sciatic nerve regeneration after a standardized crush injury in the rat. Microsurgery. 2008; 28 (6): 458-470
    • Varejão, A. S. P., Cabrita, A. M., Meek, M. F., Bulas-Cruz, J., Filipe, V. M., Gabriel, R. C., Ferreira, A. J., Geuna, S., Winter, D. A.. Ankle kinematics to evaluate functional recovery in crushed rat sciatic nerve. Muscle and Nerve. 2003; 27 (6): 706-714
    • Battiston, B., Geuna, S., Ferrero, M., Tos, P.. Nerve repair by means of tubulization: literature review and personal clinical experience comparing biological and synthetic conduits for sensory nerve repair. Microsurgery. 2005; 25 (4): 258-267
    • Amado, S., Simões, M. J., Armada da Silva, P. A. S., Luís, A. L., Shirosaki, Y., Lopes, M. A., Santos, J. D., Fregnan, F., Gambarotta, G., Raimondo, S., Fornaro, M., Veloso, A. P., Varejão, A. S. P., Maurício, A. C., Geuna, S.. Use of hybrid chitosan membranes and N1E-115 cells for promoting nerve regeneration in an axonotmesis rat model. Biomaterials. 2008; 29 (33): 4409-4419
    • Geuna, S., Raimondo, S., Ronchi, G., di Scipio, F., Tos, P., Czaja, K., Fornaro, M.. Chapter 3: histology of the peripheral nerve and changes occurring during nerve regeneration. International Review of Neurobiology. 2009; 87: 27-46
    • Shin, R. H., Friedrich, P. F., Crum, B. A., Bishop, A. T., Shin, A. Y.. Treatment of a segmental nerve defect in the rat with use of bioabsorbable synthetic nerve conduits: a comparison of commercially available conduits. The Journal of Bone and Joint Surgery. American. 2009; 91 (9): 2194-2204
    • Manczak, M., Mao, P., Nakamura, K., Bebbington, C., Park, B., Reddy, P. H.. Neutralization of granulocyte macrophage colony-stimulating factor decreases amyloid beta 1-42 and suppresses microglial activity in a transgenic mouse model of Alzheimer's disease. Human Molecular Genetics. 2009; 18 (20): 3876-3893
    • Choong, P.-F., Mok, P.-L., Cheong, S.-K., Leong, C.-F., Then, K.-Y.. Generating neuron-like cells from BM-derived mesenchymal stromal cells in vitro. Cytotherapy. 2007; 9 (2): 170-183
    • Paden, C. M., Watt, J. A., Selong, T. H., Paterson, C. L., Cranston, H. J.. The neuronal growth-associated protein (GAP)-43 is expressed by corticotrophs in the rat anterior pituitary after adrenalectomy. Endocrinology. 2006; 147 (2): 952-958
    • Thalhammer, J. G., Vladimirova, M., Bershadsky, B., Strichartz, G. R.. Neurologic evaluation of the rat during sciatic nerve block with lidocaine. Anesthesiology. 1995; 82 (4): 1013-1025
    • Koka, R., Hadlock, T. A.. Quantification of functional recovery following rat sciatic nerve transection. Experimental Neurology. 2001; 168 (1): 192-195
    • Masters, D. B., Berde, C. B., Dutta, S. K., Griggs, C. T., Hu, D., Kupsky, W., Langer, R.. Prolonged regional nerve blockade by controlled release of local anesthetic from a biodegradable polymer matrix. Anesthesiology. 1993; 79 (2): 340-346
    • Hu, D., Hu, R., Berde, C. B.. Neurologic evaluation of infant and adult rats before and after sciatic nerve blockade. Anesthesiology. 1997; 86 (4): 957-965
    • Shir, Y., Zeltser, R., Vatine, J.-J., Carmi, G., Belfer, I., Zangen, A., Overstreet, D., Raber, P., Seltzer, Z.. Correlation of intact sensibility and neuropathic pain-related behaviors in eight inbred and outbred rat strains and selection lines. Pain. 2001; 90 (1-2): 75-82
    • Varejão, A. S. P., Cabrita, A. M., Meek, M. F., Bulas-Cruz, J., Melo-Pinto, P., Raimondo, S., Geuna, S., Giacobini-Robecchi, M. G.. Functional and morphological assessment of a standardized rat sciatic nerve crush injury with a non-serrated clamp. Journal of Neurotrauma. 2004; 21 (11): 1652-1670
    • Varejão, A. S. P., Melo-Pinto, P., Meek, M. F., Filipe, V. M., Bulas-Cruz, J.. Methods for the experimental functional assessment of rat sciatic nerve regeneration. Neurological Research. 2004; 26 (2): 186-194
    • Dijkstra, J. R., Meek, M. F., Robinson, P. H., Gramsbergen, A.. Methods to evaluate functional nerve recovery in adult rats: walking track analysis, video analysis and the withdrawal reflex. Journal of Neuroscience Methods. 2000; 96 (2): 89-96
    • Varejão, A. S. P., Cabrita, A. M., Meek, M. F., Bulas-Cruz, J., Gabriel, R. C., Filipe, V. M., Melo-Pinto, P., Winter, D. A.. Motion of the foot and ankle during the stance phase in rats. Muscle and Nerve. 2002; 26 (5): 630-635
    • Varejão, A. S. P., Cabrita, A. M., Geuna, S., Melo-Pinto, P., Filipe, V. M., Gramsbergen, A., Meek, M. F.. Toe out angle: a functional index for the evaluation of sciatic nerve recovery in the rat model. Experimental Neurology. 2003; 183 (2): 695-699
    • Varejão, A. S. P., Cabrita, A. M., Geuna, S., Patrício, J. A., Azevedo, H. R., Ferreira, A. J., Meek, M. F.. Functional assessment of sciatic nerve recovery: biodegradable poly (DLLA-ε-CL) nerve guide filled with fresh skeletal muscle. Microsurgery. 2003; 23 (4): 346-353
    • Raimondo, S., Fornaro, M., di Scipio, F., Ronchi, G., Giacobini-Robecchi, M. G., Geuna, S.. Chapter 5: methods and protocols in peripheral nerve regeneration experimental research—part II: morphological techniques. International Review of Neurobiology. 2009; 87: 81-103
    • di Scipio, F., Raimondo, S., Tos, P., Geuna, S.. A simple protocol for paraffin-embedded myelin sheath staining with osmium tetroxide for light microscope observation. Microscopy Research and Technique. 2008; 71 (7): 497-502
    • Grimpe, B., Silver, J.. The extracellular matrix in axon regeneration. Progress in Brain Research. 2002; 137: 333-349
    • Luria, E. A., Panasyuk, A. F., Friedenstein, A. Y.. Fibroblast colony formation from monolayer cultures of blood cells. Transfusion. 1971; 11 (6): 345-349
    • Millesi, H.. Progress in peripheral nerve reconstruction. World Journal of Surgery. 1990; 14 (6): 733-747
    • Madison, R. D., Archibald, S. J., Krarup, C.. Peripheral Nerve Injury. 1992
    • Kline, D. G., Carlstedt, T.. Spinal nerve root repair after brachial plexus injury. Journal of Neurosurgery. 2000; 93 (2, supplement): 336-338
    • Lundborg, G.. Enhancing posttraumatic nerve regeneration. Journal of the Peripheral Nervous System. 2002; 7 (3): 139-140
    • Höke, A.. Mechanisms of disease: what factors limit the success of peripheral nerve regeneration in humans?. Nature Clinical Practice Neurology. 2006; 2 (8): 448-454
    • Gordon, T., Sulaiman, O. A. R., Ladak, A.. Chapter 24: electrical stimulation for improving nerve regeneration: where do we stand?. International Review of Neurobiology. 2009; 87: 433-444
    • Matsuyama, T., Mackay, M., Midha, R.. Peripheral nerve repair and grafting techniques: a review. Neurologia Medico-Chirurgica. 2000; 40 (4): 187-199
    • Lundborg, G.. Alternatives to autologous nerve grafts. Handchirurgie, Mikrochirurgie, Plastische Chirurgie. 2004; 36 (1): 1-7
    • Siemionow, M., Brzezicki, G.. Chapter 8: current techniques and concepts in peripheral nerve repair. International Review of Neurobiology. 2009; 87: 141-172
    • May, M.. Trauma to the facial nerve. Otolaryngologic Clinics of North America. 1983; 16 (3): 661-670
    • Doolabh, V. B., Hertl, M. C., Mackinnon, S. E.. The role of conduits in nerve repair: a review. Reviews in the Neurosciences. 1996; 7 (1): 47-84
    • Schmidt, C. E., Leach, J. B.. Neural tissue engineering: strategies for repair and regeneration. Annual Review of Biomedical Engineering. 2003; 5: 293-347
    • Chen, M. B., Zhang, F., Lineaweaver, W. C.. Luminal fillers in nerve conduits for peripheral nerve repair. Annals of Plastic Surgery. 2006; 57 (4): 462-471
    • Battiston, B., Raimondo, S., Tos, P., Gaidano, V., Audisio, C., Scevola, A., Perroteau, I., Geuna, S.. Chapter 11: tissue engineering of peripheral nerves. International Review of Neurobiology. 2009; 87: 227-249
    • Jensen, J. N., Tung, T. H. H., Mackinnon, S. E., Brenner, M. J., Hunter, D. A.. Use of anti-CD40 ligand monoclonal antibody as antirejection therapy in a murine peripheral nerve allograft model. Microsurgery. 2004; 24 (4): 309-315
    • den Dunnen, W. F., Meek, M. F., Grijpma, D. W., Robinson, P. H., Schakenraad, J. M.. In vivo and in vitro degradation of poly[(50)/(50) ((85)/(15)(L)/(D))LA/epsilon-CL], and the implications for the use in nerve reconstruction. Journal of Biomedical Materials Research. 2000; 51 (4): 575-585
    • den Dunnen, W. F. A., van der Lei, B., Robinson, P. H., Holwerda, A., Pennings, A. J., Schakenraad, J. M.. Biological performance of a degradable poly(lactic acid-ε-caprolactone) nerve guide: influence of tube dimensions. Journal of Biomedical Materials Research. 1995; 29 (6): 757-766
    • den Dunnen, W. F., van der Lei, B., Schakenraad, J. M., Stokroos, I., Blaauw, E., Bartels, H., Pennings, A. J., Robinson, P. H.. Poly(DL-lactide-epsilon-caprolactone) nerve guides perform better than autologous nerve grafts. Microsurgery. 1996; 17 (7): 348-357
    • Jansen, K., Meek, M. F., van der Werff, J. F. A., van Wachem, P. B., van Luyn, M. J. A.. Long-term regeneration of the rat sciatic nerve through a biodegradable poly(DL-lacticle-ε-caprolactone) nerve guide: tissue reactions with focus on collagen III/IV reformation. Journal of Biomedical Materials Research A. 2004; 69 (2): 334-341
    • Mackinnon, S. E., Hudson, A. R., Hunter, D. A.. Histologic assessment of nerve regeneration in the rat. Plastic and Reconstructive Surgery. 1985; 75 (3): 384-388
    • van Neerven, S. G. A., Bozkurt, A., O'Dey, D. M., Scheffel, J., Boecker, A. H., Stromps, J.-P., Dunda, S., Brook, G. A., Pallua, N.. Retrograde tracing and toe spreading after experimental autologous nerve transplantation and crush injury of the sciatic nerve: a descriptive methodological study. Journal of Brachial Plexus and Peripheral Nerve Injury. 2012; 7 (1, article 5)
    • Sunderland, I. R. P., Brenner, M. J., Singham, J., Rickman, S. R., Hunter, D. A., Mackinnon, S. E.. Effect of tension on nerve regeneration in rat sciatic nerve transection model. Annals of Plastic Surgery. 2004; 53 (4): 382-387
    • Bertani, N., Malatesta, P., Volpi, G., Sonego, P., Perris, R.. Neurogenic potential of human mesenchymal stem cells revisited: analysis by immunostaining, time-lapse video and microarray. Journal of Cell Science. 2005; 118 (17): 3925-3936
    • Woodbury, D., Reynolds, K., Black, I. B.. Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis. Journal of Neuroscience Research. 2002; 69 (6): 908-917
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