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Bone marrow stromal cells-loaded chitosan conduits promote repair of complete transection injury in rat spinal cord

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Abstract

In this study, a chitosan conduit loaded with bone marrow stromal cells (BMSCs) was developed to bridge the gap in the transected spinal cord of adult rats, and the nerve repair outcomes were evaluated by functional and histological techniques at 12 weeks after implantation. As compared to chitosan conduits alone, incorporation of BMSCs within chitosan conduits yielded additional improving effects on nerve regeneration and function restoration. The measurements with the Basso, Beattie and Bresnahan locomotor rating scale or of motor evoked potentials indicated that motor functional recovery was enhanced; retrograde tracing confirmed that the ascending tract was regenerated and the neural pathway was established; and histological analyses revealed that axon growth and remyelination in the regenerated nerve was promoted. The three-dimensional reconstruction showed that the chitosan conduit loaded with BMSCs significantly reduced the spinal cord cavity volume at the injured site. Taken together, the results collectively suggest that implantation with BMSCs-loaded chitosan conduits may become a promising approach to the repair of spinal cord injury.

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References

  1. Willerth SM, Sakiyama-Elbert SE. Cell therapy for spinal cord regeneration. Adv Drug Deliv Rev. 2008;60(2):263–76.

    Article  CAS  Google Scholar 

  2. He P, Davis SS, Illum L. In vitro evaluation of the mucoadhesive properties of chitosan microspheres. Int J Pharm. 1998;166(1):75–88.

    Article  CAS  Google Scholar 

  3. Yang Y, Hu W, Wang X, Gu X. The controlling biodegradation of chitosan fibers by N-acetylation in vitro and in vivo. J Mater Sci Mater Med. 2007;18:2117–21.

    Article  CAS  Google Scholar 

  4. Gan Q, Wang T, Cochrane C, McCarron P. Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. Colloids Surf B. 2005;44(2–3):65–73.

    Article  CAS  Google Scholar 

  5. Cheng M, Cao W, Gao Y, Gong Y, Zhao N, Zhang X. Studies on nerve cell affinity of biodegradable modified chitosan films. J Biomater Sci Polym Ed. 2003;14(10):1155–67.

    Article  CAS  Google Scholar 

  6. Yuan Y, Zhang P, Yang Y, Wang X, Gu X. The interaction of Schwann cells with chitosan membranes and fibres in vitro. Biomaterials. 2004;25(18):4273–8.

    Article  CAS  Google Scholar 

  7. Scanga VI, Goraltchouk A, Nussaiba N, Shoichet MS, Morshead CM. Biomaterials for neural-tissue engineering—chitosan supports the survival, migration, and differentiation of adult-derived neural stem and progenitor cells. Can J Chem. 2010;88(3):277–87.

    Article  CAS  Google Scholar 

  8. Cho Y, Shi RY, Borgens RB. Chitosan produces potent neuroprotection and physiological recovery following traumatic spinal cord injury. J Exp Biol. 2010;213(9):1513–20.

    Article  CAS  Google Scholar 

  9. Yang YM, Liu M, Gu Y, Lin SY, Ding F, Gu XS. Effect of chitooligosaccharide on neuronal differentiation of PC-12 cells. Cell Biol Int. 2009;33(3):352–6.

    Article  CAS  Google Scholar 

  10. Khodagholi F, Eftekharzadeh B, Maghsoudi N, Rezaei PF. Chitosan prevents oxidative stress-induced amyloid beta formation and cytotoxicity in NT2 neurons: involvement of transcription factors Nrf2 and NF-kappa β. Mol Cell Biochem. 2010;337(1–2):39–51.

    Article  CAS  Google Scholar 

  11. Ogawa Y, Sawamoto K, Miyata T, Miyao S, Watanabe M, Nakamura M, Bregman BS, Koike M, Uchiyama Y, Toyama Y, Okano H. Transplantation of in vitro-expanded fetal neural progenitor cells results in neurogenesis and functional recovery after spinal cord contusion injury in adult rats. J Neurosci Res. 2002;69(6):925–33.

    Article  CAS  Google Scholar 

  12. Kulbatski I, Mothe AJ, Nomura H, Tator CH. Endogenous and exogenous CNS derived stem/progenitor cell approaches for neurotrauma. Curr Drug Targets. 2005;6(1):111–26.

    Article  CAS  Google Scholar 

  13. Novikova LN, Pettersson J, Brohlin M, Wiberg M, Novikov LN. Biodegradable poly-beta-hydroxybutyrate scaffold seeded with Schwann cells to promote spinal cord repair. Biomaterials. 2008;29(9):1198–206.

    Article  CAS  Google Scholar 

  14. Olson HE, Rooney GE, Gross L, Nesbitt JJ, Galvin KE, Knight A, Chen B, Yaszemski MJ, Windebank AJ. Neural stem cell- and Schwann cell-loaded biodegradable polymer scaffolds support axonal regeneration in the transected spinal cord. Tissue Eng Part A. 2009;15(7):1797–805.

    Article  CAS  Google Scholar 

  15. Steward O, Sharp K, Selvan G, Hadden A, Hofstadter M, Au E, Roskams J. A re-assessment of the consequences of delayed transplantation of olfactory lamina propria following complete spinal cord transection in rats. Exp Neurol. 2006;198(2):483–99.

    Article  Google Scholar 

  16. Nomura H, Zahir T, Kim H, Katayama Y, Kulbatski I, Morshead CM, Shoichet MS, Tator CH. Extramedullary chitosan channels promote survival of transplanted neural stem and progenitor cells and create a tissue bridge after complete spinal cord transection. Tissue Eng Part A. 2008;14(5):649–65.

    Article  CAS  Google Scholar 

  17. Tohill M, Mantovani C, Wiberg M, Terenghi G. Rat bone marrow mesenchymal stem cells express glial markers and stimulate nerve regeneration. Neurosci Lett. 2004;362(3):200–3.

    Article  CAS  Google Scholar 

  18. Jin K, Mao XO, Batteur S, Sun Y, Greenberg DA. Induction of neuronal markers in bone marrow cells: differential effects of growth factors and patterns of intracellular expression. Exp Neurol. 2003;184(1):78–89.

    Article  CAS  Google Scholar 

  19. Woodbury D, Schwarz EJ, Prockop DJ, Black IB. Adult rat and human bone marrow stromal cells differentiate into neurons. J Neurosci Res. 2000;61(4):364–70.

    Article  CAS  Google Scholar 

  20. 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(19):10711–6.

    Article  CAS  Google Scholar 

  21. Ankeny DP, McTigue DM, Jakeman LB. Bone marrow transplants provide tissue protection and directional guidance for axons after contusive spinal cord injury in rats. Exp Neurol. 2004;190(1):17–31.

    Article  Google Scholar 

  22. Rooney GE, McMahon SS, Ritter T, Garcia Y, Moran C, Madigan NN, Flügel A, Dockery P, O’Brien T, Howard L, Windebank AJ, Barry FP. Neurotrophic factor-expressing mesenchymal stem cells survive transplantation into the contused spinal cord without differentiating into neural cells. Tissue Eng Part A. 2009;15(10):3049–59.

    Article  CAS  Google Scholar 

  23. Vaquero J, Zurita M, Oya S, Santos M. Cell therapy using bone marrow stromal cells in chronic paraplegic rats: systemic or local administration? Neurosci Lett. 2006;398(1–2):129–34.

    Article  CAS  Google Scholar 

  24. Zurita M, Vaquero J. Bone marrow stromal cells can achieve cure of chronic paraplegic rats: functional and morphological outcome one year after transplantation. Neurosci Lett. 2006;402(1–2):51–6.

    Article  CAS  Google Scholar 

  25. Ishikawa N, Suzuki Y, Dezawa M, Kataoka K, Ohta M, Cho H, Ide C. Peripheral nerve regeneration by transplantation of BMSC-derived Schwann cells as chitosan gel sponge scaffolds. J Biomed Mater Res A. 2009;89(4):1118–24.

    Google Scholar 

  26. Chen X, Wang XD, Chen G, Lin WW, Yao J, Gu XS. Study of in vivo differentiation of rat bone marrow stromal cells into Schwann cell-like cells. Microsurgery. 2006;26(2):111–5.

    Article  CAS  Google Scholar 

  27. Lin W, Chen X, Wang X, Liu J, Gu X. Adult rat bone marrow stromal cells differentiate into Schwann cell-like cells in vitro. In Vitro Cell Dev Biol Anim. 2008;44(1–2):31–40.

    Article  CAS  Google Scholar 

  28. Wang X, Hu W, Cao Y, Yao J, Wu J, Gu X. Dog sciatic nerve regeneration across a 30-mm defect bridged by a chitosan/PGA artificial nerve graft. Brain. 2005;128(8):1897–910.

    Article  Google Scholar 

  29. Basso DM, Beattie MS, Bresnahan JC. A sensitive and reliable locomotor rating scale for open field testing in rats. J Neurotrauma. 1995;12(1):1–21.

    Article  CAS  Google Scholar 

  30. Onifer SM, Rabchevsky AG, Scheff SW. Rat models of traumatic spinal cord injury to assess motor recovery. ILAR J. 2007;48(4):385–95.

    CAS  Google Scholar 

  31. David S, Lacroix S. Molecular approaches to spinal cord repair. Annu Rev Neurosci. 2003;26:411–40.

    Article  CAS  Google Scholar 

  32. Kakulas BA. Neuropathology: the foundation for new treatments in spinal cord injury. Spinal Cord. 2004;42(10):549–63.

    Article  CAS  Google Scholar 

  33. Syková E, Jendelová P, Urdzíková L, Lesný P, Hejcl A. Bone marrow stem cells and polymer hydrogels—two strategies for spinal cord injury repair. Cell Mol Neurobiol. 2006;26(7–8):1113–29.

    Google Scholar 

  34. Hejcl A, Lesný P, Prádný M, Michálek J, Jendelová P, Stulík J, Syková E. Biocompatible hydrogels in spinal cord injury repair. Physiol Res. 2008;57(3 Suppl):S121–32. Epub 2008 May 13. Review.

    CAS  Google Scholar 

  35. Busch SA, Horn KP, Cuascut FX, Hawthorne AL, Bai L, Miller RH, Silver J. Adult NG2+ cells are permissive to neurite outgrowth and stabilize sensory axons during macrophage-induced axonal dieback after spinal cord injury. J Neurosci. 2010;30(1):255–65.

    Article  CAS  Google Scholar 

  36. Itoh S, Suzuki M, Yamaguchi I, Takakuda K, Kobayashi H, Shinomiya K, Tanaka J. Development of a nerve scaffold using a tendon chitosan tube. Artif Organs. 2003;27(12):1079–88.

    Article  Google Scholar 

  37. Barry FP, Murphy JM, English K, Mahon BP. Immunogenicity of adult mesenchymal stem cells: lessons from the fetal allograft. Stem Cells Dev. 2005;14(3):252–65.

    Article  CAS  Google Scholar 

  38. Moreau JL, Xu HH. Mesenchymal stem cell proliferation and differentiation on an injectable calcium phosphate-chitosan composite scaffold. Biomaterials. 2009;30(14):2675–82.

    Article  CAS  Google Scholar 

  39. Zhang J, Li Y, Lu M, Cui Y, Chen J, Noffsinger L, Elias SB, Chopp M. Bone marrow stromal cells reduce axonal loss in experimental autoimmune encephalomyelitis mice. J Neurosci Res. 2006;84(3):587–95.

    Article  CAS  Google Scholar 

  40. Li X, Yang Z, Zhang A, Wang T, Chen W. Repair of thoracic spinal cord injury by chitosan tube implantation in adult rats. Biomaterials. 2009;30(6):1121–32.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by grant from Natural Science Foundation of China, No. 30870643 and Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions. We thank Professor Jie Liu for assistance in manuscript preparation.

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Authors and Affiliations

  1. Department of Histology and Embryology, Medical College, Nantong University, Nantong, 226001, Jiangsu, China

    Xue Chen, Yang Yang, Jian Yao, Weiwei Lin, Yi Li, Ying Chen & Xiaodong Wang

  2. Department of Neurosurgery, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China

    Yilu Gao & Xiaodong Wang

  3. Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, 226001, Jiangsu, China

    Yumin Yang, Xiaosong Gu & Xiaodong Wang

Authors
  1. Xue Chen
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  2. Yang Yang
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  3. Jian Yao
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  4. Weiwei Lin
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  5. Yi Li
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  9. Xiaosong Gu
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  10. Xiaodong Wang
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Corresponding author

Correspondence to Xiaodong Wang.

Additional information

Xue Chen and Yang Yang contributed equally to this work.

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Chen, X., Yang, Y., Yao, J. et al. Bone marrow stromal cells-loaded chitosan conduits promote repair of complete transection injury in rat spinal cord. J Mater Sci: Mater Med 22, 2347 (2011). https://doi.org/10.1007/s10856-011-4401-9

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