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Human Amniotic Fluid Mesenchymal Stem Cells in Combination with Hyperbaric Oxygen Augment Peripheral Nerve Regeneration

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Purpose Attenuation of pro-inflammatory cytokines and associated inflammatory cell deposits rescues human amniotic fluid mesenchymal stem cells (AFS) from apoptosis. Hyperbaric oxygen (HBO) suppressed stimulus-induced pro-inflammatory cytokine production in blood-derived monocyte-macrophages. Herein, we evaluate the beneficial effect of hyperbaric oxygen on transplanted AFS in a sciatic nerve injury model. Methods Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. Hyperbaric oxygen (100% oxygen, 2 ATA, 60 min/day) was administered 12 h after operation for seven consecutive days. Transplanted cell apoptosis, oxidative stress, inflammatory cell deposits and associated chemokines, pro-inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 and 28 days after injury. Results Crush injury induced an inflammatory response, disrupted nerve integrity, and impaired nerve function in the sciatic nerve. However, crush injury-provoked inflammatory cytokines, deposits of inflammatory cytokines, and associated macrophage migration chemokines were attenuated in groups receiving hyperbaric oxygen but not in the AFS-only group. No significant increase in oxidative stress was observed after administration of HBO. In transplanted AFS, marked apoptosis was detected and this event was reduced by HBO treatment. Increased nerve myelination and improved motor function were observed in AFS-transplant, HBO-administrated, and AFS/HBO-combined treatment groups. Significantly, the AFS/HBO combined treatment showed the most beneficial effect. Conclusion AFS in combination with HBO augment peripheral nerve regeneration, which may involve the suppression of apoptotic death in implanted AFS and the attenuation of an inflammatory response detrimental to peripheral nerve regeneration.

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References

  1. Diao E, Vannuyen T (2000) Techniques for primary nerve repair. Hand Clin 16:53–66

    PubMed  CAS  Google Scholar 

  2. Campbell WW (2008) Evaluation and management of peripheral nerve injury. Clin Neurophysiol 119:1951–1965. doi:10.1016/j.clinph.2008.03.018

    Article  PubMed  Google Scholar 

  3. Frostick SP (1995) The physiological and metabolic consequences of muscle denervation. Int Angiol 14:278–287. doi:10.1159/000109803

    PubMed  CAS  Google Scholar 

  4. Pollock M (1995) Nerve regeneration. Curr Opin Neurol 8:354–358. doi:10.1097/00019052-199510000-00005

    Article  PubMed  CAS  Google Scholar 

  5. Murakami T, Fujimoto Y, Yasunaga Y, Ishida O, Tanaka N, Ikuta Y, Ochi M (2003) Transplanted neuronal progenitor cells in a peripheral nerve gap promote nerve repair. Brain Res 974:17–24. doi:10.1016/S0006-8993(03)02539-3

    Article  PubMed  CAS  Google Scholar 

  6. Pan HC, Yang DY, Chiu YT, Lai SZ, Wang YC, Chang MH, Cheng FC (2006) Enhanced regeneration in injured sciatic nerve by human amniotic mesenchymal stem cell. J Clin Neurosci 13:570–575. doi:10.1016/j.jocn.2005.06.007

    Article  PubMed  Google Scholar 

  7. Pan HC, Cheng FC, Chen CJ, Lai SZ, Lee CW, Yang DY, Chang MH, Ho SP (2007) Post-injury regeneration in rat sciatic nerve facilitated by neurotrophic factors secreted by amniotic fluid mesenchymal stem cells. J Clin Neurosci 14:1089–1098. doi:10.1016/j.jocn.2006.08.008

    Article  PubMed  CAS  Google Scholar 

  8. Shen ZL, Lassner F, Becker M, Walter GF, Bader A, Berger A (1999) Viability of cultured nerve grafts: an assessment of proliferation of Schwann cells and fibroblasts. Microsurgery 19:356–363. doi :10.1002/(SICI)1098-2752(1999)19:8<356::AID-MICR2>3.0.CO;2-N

    Article  PubMed  CAS  Google Scholar 

  9. Dezawa M, Takahashi I, Esaki M, Takano M, Sawada H (2001) Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. Eur J Neurosci 14:1771–1776. doi:10.1046/j.0953-816x.2001.01814.x

    Article  PubMed  CAS  Google Scholar 

  10. Tompach PC, Lew D, Stoll JL (1997) Cell response to hyperbaric oxygen treatment. Int J Oral Maxillofac Surg 26:82–86. doi:10.1016/S0901-5027(05)80632-0

    Article  PubMed  CAS  Google Scholar 

  11. Kang TS, Gorti GK, Quan SY, Ho M, Koch RJ (2004) Effect of hyperbaric oxygen on the growth factor profile of fibroblasts. Arch Facial Plast Surg 6:31–35. doi:10.1001/archfaci.6.1.31

    Article  PubMed  Google Scholar 

  12. Thom SR, Bhopale VM, Velazquez OC, Goldstein LJ, Thom LH, Buerk DG (2006) Stem cell mobilization by hyperbaric oxygen. Am J Physiol Heart Circ Physiol 290:H1378–H1386. doi:10.1152/ajpheart.00888.2005

    Article  PubMed  CAS  Google Scholar 

  13. Goldstein LJ, Gallagher KA, Bauer SM, Bauer RJ, Baireddy V, Liu ZJ, Buerk DG, Thom SR, Velazquez OC (2006) Endothelial progenitor cell release into circulation is triggered by hyperoxia-induced increases in bone marrow nitric oxide. Stem Cells 24:2309–2318. doi:10.1634/stemcells.2006-0010

    Article  PubMed  CAS  Google Scholar 

  14. Milovanova TN, Bhopale VM, Sorokina EM, Moore JS, Hunt TK, Hauer-Jensen M, Velazquez OC, Thom SR (2008) Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo. J Appl Physiol epub Nov. 20

  15. Shyu KG, Hung HF, Wang BW, Chang H (2008) Hyperbaric oxygen induces placental growth factor expression in bone marrow-derived mesenchymal stem cells. Life Sci 83:65–73. doi:10.1016/j.lfs.2008.05.005

    Article  PubMed  CAS  Google Scholar 

  16. Wang XL, Zhao YS, Yang YJ, Xie M, Yu XH (2008) Therapeutic window of hyperbaric oxygen therapy for hypoxic-ischemic brain damage in newborn rats. Brain Res 1222:87–94. doi:10.1016/j.brainres.2008.05.016

    Article  PubMed  CAS  Google Scholar 

  17. Wang XL, Yang YJ, Xie M, Yu XH, Liu CT, Wang X (2007) Proliferation of neural stem cells correlates with Wnt-3 protein in hypoxic-ischemic neonate rats after hyperbaric oxygen therapy. Neuroreport 18:1753–1756

    Article  PubMed  CAS  Google Scholar 

  18. Haapaniemi T, Nylander G, Kanje M, Dahlin L (1998) Hyperbaric oxygen treatment enhances regeneration of the rat sciatic nerve. Exp Neurol 149:433–438. doi:10.1006/exnr.1997.6745

    Article  PubMed  CAS  Google Scholar 

  19. Akin ML, Gulluoglu BM, Uluutku H (2002) Hyperbaric oxygen improve healing in experimental rat colitis. Undersea Hyperb Med 29:279–285

    PubMed  CAS  Google Scholar 

  20. Luongo C, Imperatore F, Cuzzocrea S, Filippelli A, Scafuro MA, Mangoni G, Portolano F, Rossi F (1998) Effects of hyperbaric oxygen exposure on a zymosan-induced shock model. Crit Care Med 26:1972–1976. doi:10.1097/00003246-199812000-00022

    Article  PubMed  CAS  Google Scholar 

  21. Benson RM, Minter LM, Osborne BA, Granowitz EV (2003) Hyperbaric oxygen inhibits stimulus-induced proinflammatory cytokine synthesis by human blood-derived monocyte-macrophages. Clin Exp Immunol 134:57–62. doi:10.1046/j.1365-2249.2003.02248.x

    Article  PubMed  CAS  Google Scholar 

  22. Tsai MS, Hwang SM, Tsai YL, Cheng FC, Lee JL, Chang YJ (2006) Clonal amniotic fluid-derived stem cells express characteristics of both mesenchymal and neural stem cells. Biol Reprod 74:545–551. doi:10.1095/biolreprod.105.046029

    Article  PubMed  CAS  Google Scholar 

  23. Pan HC, Chen CJ, Cheng FC, Ho SP, Liu MJ, Hwang SM, Chang MH, Wang YC (2008) Combination of G-CSF administration and human amniotic fluid mesenchymal stem cell transplantation promotes peripheral nerve regeneration. Neurochem Res epub Aug. 9

  24. Taskinen HS, Olsson T, Bucht A, Khademi M, Svelander L, Roytta M (2000) Peripheral nerve injury induces endoneurial expression of IFN-gamma, IL-10 and TNF-alpha mRNA. J Neuroimmunol 102:17–25. doi:10.1016/S0165-5728(99)00154-X

    Article  PubMed  CAS  Google Scholar 

  25. Moertel CA, Stupca PJ, Dewald GW (1992) Pseudomosaicism, true mosaicism, and maternal cell contamination in amniotic fluid processed with in situ culture and robotic harvesting. Prenat Diagn 12:671–683. doi:10.1002/pd.1970120808

    Article  PubMed  CAS  Google Scholar 

  26. Syroid DE, Maycox PJ, Soilu-Hanninen M, Petratos S, Bucci T, Burrola P, Murray S, Cheema S, Lee KF, Lemke G, Kilpatrick TJ (2000) Induction of postnatal schwann cell death by the low-affinity neurotrophin receptor in vitro and after axotomy. J Neurosci 20:5741–5747

    PubMed  CAS  Google Scholar 

  27. Chiavegato A, Bollini S, Pozzobon M, Callegari A, Gasparotto L, Taiani J, Piccoli M, Lenzini E, Gerosa G, Vendramin I, Cozzi E, Angelini A, Iop L, Zanon GF, Atala A, De Coppi P, Sartore S (2007) Human amniotic fluid-derived stem cells are rejected after transplantation in the myocardium of normal, ischemic, immuno-suppressed or immuno-deficient rat. J Mol Cell Cardiol 42:746–759. doi:10.1016/j.yjmcc.2006.12.008

    Article  PubMed  CAS  Google Scholar 

  28. Santos PM (2000) A functional model system of an hypoxic nerve injury and its evaluation. Laryngoscope 110:845–853. doi:10.1097/00005537-200005000-00014

    Article  PubMed  CAS  Google Scholar 

  29. Alleva R, Nasole E, Di Donato F, Borghi B, Neuzil J, Tomasetti M (2005) Alpha-Lipoic acid supplementation inhibits oxidative damage, accelerating chronic wound healing in patients undergoing hyperbaric oxygen therapy. Biochem Biophys Res Commun 333:404–410. doi:10.1016/j.bbrc.2005.05.119

    Article  PubMed  CAS  Google Scholar 

  30. Benedetti S, Lamorgese A, Piersantelli M, Pagliarani S, Benvenuti F, Canestrari F (2004) Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. Clin Biochem 37:312–317. doi:10.1016/j.clinbiochem.2003.12.001

    Article  PubMed  CAS  Google Scholar 

  31. Chavko M, Harabin AL (1996) Regional lipid peroxidation and protein oxidation in rat brain after hyperbaric oxygen exposure. Free Radic Biol Med 20:973–978. doi:10.1016/0891-5849(95)02181-7

    Article  PubMed  CAS  Google Scholar 

  32. Dennog C, Gedik C, Wood S, Speit G (1999) Analysis of oxidative DNA damage and HPRT mutations in humans after hyperbaric oxygen treatment. Mutat Res 431:351–359. doi:10.1016/S0027-5107(99)00178-5

    PubMed  CAS  Google Scholar 

  33. Wada K, Miyazawa T, Nomura N, Tsuzuki N, Nawashiro H, Shima K (2001) Preferential conditions for and possible mechanisms of induction of ischemic tolerance by repeated hyperbaric oxygenation in gerbil hippocampus. Neurosurgery 49:160–166. Discussion 166–167. doi:10.1097/00006123-200107000-00025

    Google Scholar 

  34. Ay H, Topal T, Ozler M, Uysal B, Korkmaz A, Oter S, Ogur R, Dundar K (2007) Persistence of hyperbaric oxygen-induced oxidative effects after exposure in rat brain cortex tissue. Life Sci 80:2025–2029. doi:10.1016/j.lfs.2007.03.002

    Article  PubMed  CAS  Google Scholar 

  35. Sumen G, Cimsit M, Eroglu L (2001) Hyperbaric oxygen treatment reduces carrageenan-induced acute inflammation in rats. Eur J Pharmacol 431:265–268. doi:10.1016/S0014-2999(01)01446-7

    Article  PubMed  CAS  Google Scholar 

  36. Warren J, Sacksteder MR, Thuning CA (1979) Therapeutic effect of prolonged hyperbaric oxygen in adjuvant arthritis of the rat. Arthritis Rheum 22:334–339. doi:10.1002/art.1780220404

    Article  PubMed  CAS  Google Scholar 

  37. Tokar B, Gundogan AH, Ilhan H, Bildirici K, Gultepe M, Elbuken E (2003) The effect of hyperbaric oxygen treatment on the inflammatory changes caused by intraperitoneal meconium. Pediatr Surg Int 19:673–676. doi:10.1007/s00383-003-1036-z

    Article  PubMed  CAS  Google Scholar 

  38. Chen SY, Chen YC, Wang JK, Hsu HP, Ho PS, Chen YC, Sytwu HK (2003) Early hyperbaric oxygen therapy attenuates disease severity in lupus-prone autoimmune (NZB × NZW) F1 mice. Clin Immunol 108:103–110. doi:10.1016/S1521-6616(03)00091-3

    Article  PubMed  CAS  Google Scholar 

  39. Brenner I, Shephard RJ, Shek PN (1999) Immune function in hyperbaric environments, diving, and decompression. Undersea Hyperb Med 26:27–39

    PubMed  CAS  Google Scholar 

  40. Murphey SA, Hyams JS, Fisher AB, Root RK (1975) Effects of oxygen exposure on it vitro function of pulmonary alveolar macrophages. J Clin Invest 56:503–511. doi:10.1172/JCI108117

    Article  PubMed  CAS  Google Scholar 

  41. Inamoto Y, Okuno F, Saito K, Tanaka Y, Watanabe K, Morimoto I, Yamashita U, Eto S (1991) Effect of hyperbaric oxygenation on macrophage function in mice. Biochem Biophys Res Commun 179:886–891. doi:10.1016/0006-291X(91)91901-N

    Article  PubMed  CAS  Google Scholar 

  42. Lahat N, Bitterman H, Yaniv N, Kinarty A, Bitterman N (1995) Exposure to hyperbaric oxygen induces tumour necrosis factor-alpha (TNF-alpha) secretion from rat macrophages. Clin Exp Immunol 102:655–659

    Article  PubMed  CAS  Google Scholar 

  43. Weisz G, Lavy A, Adir Y, Melamed Y, Rubin D, Eidelman S, Pollack S (1997) Modification of in vivo and in vitro TNF-alpha, IL-1, and IL-6 secretion by circulating monocytes during hyperbaric oxygen treatment in patients with perianal Crohn’s disease. J Clin Immunol 17:154–159. doi:10.1023/A:1027378532003

    Article  PubMed  CAS  Google Scholar 

  44. Perrin FE, Lacroix S, Aviles-Trigueros M, David S (2005) Involvement of monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha and interleukin-1beta in Wallerian degeneration. Brain 128:854–866. doi:10.1093/brain/awh407

    Article  PubMed  Google Scholar 

  45. Shamash S, Reichert F, Rotshenker S (2002) The cytokine network of Wallerian degeneration: tumor necrosis factor-alpha, interleukin-1alpha, and interleukin-1beta. J Neurosci 22:3052–3060

    PubMed  CAS  Google Scholar 

  46. Varejao AS, Cabrita AM, Meek MF, Bulas-Cruz J, Melo-Pinto P, Raimondo S, Geuna S, Giacobini-Robecchi MG (2004) Functional and morphological assessment of a standardized rat sciatic nerve crush injury with a non-serrated clamp. J Neurotrauma 21:1652–1670

    PubMed  Google Scholar 

  47. Omura K, Ohbayashi M, Sano M, Omura T, Hasegawa T, Nagano A (2004) The recovery of blood-nerve barrier in crush nerve injury—a quantitative analysis utilizing immunohistochemistry. Brain Res 1001:13–21. doi:10.1016/j.brainres.2003.10.067

    Article  PubMed  CAS  Google Scholar 

  48. Mata M, Alessi D, Fink DJ (1990) S-100 is preferentially distributed in myelin-forming Schwann cells. J Neurocytol 19:432–442. doi:10.1007/BF01188409

    Article  PubMed  CAS  Google Scholar 

  49. Krampera M, Pasini A, Pizzolo G, Cosmi L, Romagnani S, Annunziato F (2006) Regenerative and immunomodulatory potential of mesenchymal stem cells. Curr Opin Pharmacol 6:435–441. doi:10.1016/j.coph.2006.02.008

    Article  PubMed  CAS  Google Scholar 

  50. DeMedicanelli L, Free WJ, Wyatt RT (1982) An index of functional condition of rat sciatic nerve based on measurement made from walking tract. Exp Neurol 77:634–643. doi:10.1016/0014-4886(82)90234-5

    Article  Google Scholar 

  51. Eguiluz-Ordonez R, Sanchez CE, Venegas A, Figueroa-Granados V, Hernandez-Pando R (2006) Effects of hyperbaric oxygen on peripheral nerves. Plast Reconstr Surg 118:350–357. Discussion 358–359. doi:10.1097/01.prs.0000227666.64552.81

    Google Scholar 

  52. Martins RS, Siqueira MG, Da Silva CF, Plese JP (2005) Overall assessment of regeneration in peripheral nerve lesion repair using fibrin glue, suture, or a combination of the 2 techniques in a rat model. Which is the ideal choice? Surg Neurol 64 Suppl 1:S1:10–16; discussion S11:16

    Google Scholar 

  53. Spirck U (1991) Long-term tracing of vital neurons with Hoechst 33342 in transplantation studies. J Neurosci Methods 36:229–238. doi:10.1016/0165-0270(91)90049-6

    Article  Google Scholar 

  54. Iwashita Y, Crang AJ, Blakemore WF (2000) Redistribution of bisbenzimide Hoechst 33342 from transplanted cells to host cells. Neuroreport 11:1013–1016. doi:10.1097/00001756-200004070-00023

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by grants from the National Science Council (NSC 96-2314-B-075A-001) and Taichung Veterans General Hospital (TCVGH-964906D and TCVGH-PU968102), Taiwan, ROC. We also thank the Biostatistics Task Force of Taichung Veterans General Hospital for help with statistical analysis.

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Authors and Affiliations

  1. Department of Neurosurgery, Taichung Veterans General Hospital, Taichung, Taiwan

    Hung-Chuan Pan

  2. Department of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan

    Hung-Chuan Pan & Shu-Peng Ho

  3. Institute of Medical Technology, National Chung-Hsing University, Taichung, Taiwan

    Hung-Chuan Pan & Chung-Jung Chen

  4. Department of Chest Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

    Chun-Shih Chin

  5. Department of Neurosurgery, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan

    Dar-Yu Yang

  6. Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan

    Shiaw-Min Hwang

  7. Department of Neurology, Taichung Veterans General Hospital, Taichung, Taiwan

    Ming-Hong Chang

  8. Stem Cell Center, Department of Medical Research, Taichung Veterans General Hospital, No. 160, Sec. 3, Taichung-Kang Road, Taichung, 407, Taiwan, R.O.C.

    Fu-Chou Cheng

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  1. Hung-Chuan Pan
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Pan, HC., Chin, CS., Yang, DY. et al. Human Amniotic Fluid Mesenchymal Stem Cells in Combination with Hyperbaric Oxygen Augment Peripheral Nerve Regeneration. Neurochem Res 34, 1304–1316 (2009). https://doi.org/10.1007/s11064-008-9910-7

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