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Cellular and Molecular Neurobiology

, Volume 39, Issue 3, pp 341–353 | Cite as

Repair of Peripheral Nerve Sensory Impairments via the Transplantation of Bone Marrow Neural Tissue-Committed Stem Cell-Derived Sensory Neurons

  • Zhenhai Yu
  • Ning Xu
  • Naili Zhang
  • Yanlian Xiong
  • Zhiqiang Wang
  • Shaohua Liang
  • Dongmei Zhao
  • Fei HuangEmail author
  • Chuansen ZhangEmail author
Original Research

Abstract

The present study aimed to investigate the efficacy of transplantation of bone marrow neural tissue-committed stem cell-derived sensory neuron-like cells for the repair of peripheral nerve sensory impairments in rats. Bone marrow was isolated and cultured to obtain the neural tissue-committed stem cells (NTCSCs), and the differentiation of these cells into sensory neuron-like cells was induced. Bone marrow mesenchymal stem cells (BMSCs), bone marrow NTCSCs, and bone marrow NTCSC-derived sensory neurons (NTCSC-SNs) were transplanted by microinjection into the L4 and L5 dorsal root ganglions (DRGs) in an animal model of sensory defect. On the 2nd, 4th, 8th, and 12th week after the transplantation, the effects of the three types of stem cells on the repair of the sensory functional defect were analyzed via behavioral observation, sensory function evaluation, electrophysiological examination of the sciatic nerve, and morphological observation of the DRGs. The results revealed that the transplanted BMSCs, NTCSCs, and NTCSC-SNs were all able to repair the sensory nerves. In addition, the effect of the NTCSC-SNs was significantly better than that of the other two types of stem cells. The general posture and gait of the animals in the sensory defect model exhibited evident improvement over time. Plantar temperature sensitivity and pain sensitivity gradually recovered, and the sensation latency was reduced, with faster sensory nerve conduction velocity. Transplantation of NTCSC-SNs can improve the repair of peripheral nerve sensory defects in rats.

Keywords

Neural tissue-committed stem cells Sensory neurons Dorsal root ganglion Transplantation Neural repair 

Notes

Acknowledgements

We thank all members of the department of human anatomy of Second Military Medical University for helpful discussions and comments on the manuscript.

Author Contributions

FH and CZ carried out the concepts. ZY, NX and NZ participated in the design of this study and performed the statistical analysis. These three authors contributed to this work equally and should be considered as co-first authors. YX, ZW, SL, DZ, carried out the study and collected important background information. ZY, NX, and NZ drafted the manuscript. All authors read and approved the final manuscript.

Funding

This work was supported in part by the Shandong Provincial Natural Science Foundation, China (ZR2014HM009,2014GSF118177, BS2015SW021, 2013ws0306), Natural Science Foundation of China (81271717, 81571821) and The army subject funds of China(AWS14C001, 13CXZ028).

Compliance with Ethical Standards

Conflict of interest

The authors have declared no conflict of interest.

References

  1. Abraham R, Verfaillie CM (2012) Neural differentiation and support of neuroregeneration of non-neural adult stem cells. Prog Brain Res 201:17–34PubMedGoogle Scholar
  2. Ahmed S (2009) The culture of neural stem cells. J Cell Biochem 106(1):1–6PubMedGoogle Scholar
  3. Allodi I, Udina E, Navarro X (2012) Specificity of peripheral nerve regeneration: interactions at the axon level. Prog Neurobiol 98(1):16–37PubMedGoogle Scholar
  4. Amr SM, Gouda A, Koptan WT, Galal AA, Abdel-Fattah DS, Rashed LA, Atta HM, Abdel-Aziz MT (2014) Bridging defects in chronic spinal cord injury using peripheral nerve grafts combined with a chitosan-laminin scaffold and enhancing regeneration through them by co-transplantation with bone-marrow-derived mesenchymal stem cells: case series of 14 patients. J Spinal Cord Med 37(1):54–71PubMedPubMedCentralGoogle Scholar
  5. Andressen C (2013) Neural stem cells: from neurobiology to clinical applications. Curr Pharm Biotechnol 14(1):20–28PubMedGoogle Scholar
  6. Cao QL, Zhang YP, Howard RM, Walters WM, Tsoulfas P, Whittemore SR (2001) Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage. Exp Neurol 167(1):48–58PubMedGoogle Scholar
  7. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53(1):55–63PubMedPubMedCentralGoogle Scholar
  8. García-García A, de Castillejo CL, Méndez-Ferrer S (2015) BMSCs and hematopoiesis. Immunol Lett 168(2):129–135PubMedGoogle Scholar
  9. Gelati M, Profico D, Projetti-Pensi M, Muzi G, Sgaravizzi G, Vescovi AL (2013) Culturing and expansion of “clinical grade” precursors cells from the fetal human central nervous system. Methods Mol Biol 1059:65–77PubMedGoogle Scholar
  10. Gu Y, Wang J, Ding F, Hu N, Wang Y, Gu X (2010) Neurotrophic actions of bone marrow stromal cells on primary culture of dorsal root ganglion tissues and neurons. J Mol Neurosci 40(3):332–341PubMedGoogle Scholar
  11. Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32(1):77–88PubMedPubMedCentralGoogle Scholar
  12. He Q, Man L, Ji Y, Zhang S, Jiang M, Ding F, Gu X (2012) Comparative proteomic analysis of differentially expressed proteins between peripheral sensory and motornerves. J Proteome Res 11(6):3077–3089PubMedGoogle Scholar
  13. Helgren ME, Cliffer KD, Torrento K, Cavnor C, Curtis R, DiStefano PS, Wiegand SJ, Lindsay RM (1997) Neurotrophin-3 administration attenuates deficits of pyridoxine-induced large fiber sensory neuropathy. J Neurosci 17(1):372–382PubMedGoogle Scholar
  14. Hoffman RM (2014) Nestin-expressing hair follicle-accessible pluripotent stem cells for nerve and spinal cord repair. Cells Tissues Organs 200(1):42–47PubMedGoogle Scholar
  15. Hwang DH, Kim BG, Kim EJ, Lee SI, Joo IS, Suh-Kim H, Sohn S, Kim SU (2009) Transplantation of human neural stem cells transduced with Olig2 transcription factor improves locomotor recovery and enhances myelination in the white matter of rat spinal cord following contusive injury. BMC Neurosci 10:117PubMedPubMedCentralGoogle Scholar
  16. Iwasaki M, Wilcox JT, Nishimura Y, Zweckberger K, Suzuki H, Wang J, Liu Y, Karadimas SK, Fehlings MG (2014) Synergistic effects of self-assembling peptide and neural stem/progenitor cells to promote tissue repair and forelimb functional recovery in cervical spinal cord injury. Biomaterials 35(9):2617–2629PubMedGoogle Scholar
  17. Kabos P, Ehtesham M, Kabosova A, Black KL, Yu JS (2002) Generation of neural progenitor cells from whole adult bone marrow. Exp Neurol 178(2):288–293PubMedGoogle Scholar
  18. Kakabadze Z, Kipshidze N, Mardaleishvili K, Chutkerashvili G, Chelishvili I, Harders A, Loladze G, Shatirishvili G, Kipshidze N, Chakhunashvili D, Chutkerashvili K (2016) Phase 1 trial of autologous bone marrow stem cell transplantation in patients with spinal cord injury. Stem Cells Int 2016:6768274PubMedPubMedCentralGoogle Scholar
  19. Kamishina H, Cheeseman JA, Clemmons RM (2009) The effects of canine bone marrow stromal cells on neuritogenesis from dorsal root ganglion neurons in vitro. Vet Res Commun 33(7):645–657PubMedGoogle Scholar
  20. Kondo T, Johnson SA, Yoder MC, Romand R, Hashino E (2005) Sonic hedgehog and retinoic acid synergistically promote sensory fate specification from bone marrow-derivedpluripotent stem cells. Proc Natl Acad Sci USA 102(13):4789–4794PubMedGoogle Scholar
  21. Kucia M, Ratajczak J, Reca R, Janowska-Wieczorek A, Ratajczak MZ (2004) Tissue-specific muscle, neural and liver stem/progenitor cells reside in the bone marrow, respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury. Blood Cells Mol Dis 32(1):52–57PubMedGoogle Scholar
  22. Kucia M, Zhang YP, Reca R, Wysoczynski M, Machalinski B, Majka M, Ildstad ST, Ratajczak J, Shields CB, Ratajczak MZ (2006) Cells enriched in markers of neural tissue-committed stem cells reside in the bone marrow and are mobilized into the peripheral blood following stroke. Leukemia 20(1):18–28PubMedGoogle Scholar
  23. Liao W, Huang N, Yu J, Jares A, Yang J, Zieve G, Avila C, Jiang X, Zhang XB, Ma Y (2015) Direct conversion of cord blood CD34 + cells into neural stem cells by OCT4. Stem Cells Transl Med 4(7):755–763PubMedPubMedCentralGoogle Scholar
  24. Martens DJ, Tropepe V, van Der Kooy D (2000) Separate proliferation kinetics of fibroblast growth factor-responsive and epidermal growth factor-responsive neural stem cells within the embryonic forebrain germinal zone. J Neurosci 20(3):1085–1095PubMedGoogle Scholar
  25. Mezey E (2011) The therapeutic potential of bone marrow-derived stromal cells. J Cell Biochem 112(10):2683–2687PubMedPubMedCentralGoogle Scholar
  26. Mistriotis P, Andreadis ST (2013) Hair follicle: a novel source of multipotent stem cells for tissue engineering and regenerative medicine. Tissue Eng Part B Rev 19(4):265–278PubMedPubMedCentralGoogle Scholar
  27. Najafzadeh N, Esmaeilzade B, Imcheh MD (2015) Hair follicle stem cells: in vitro and in vivo neural differentiation. World J Stem Cells 7(5):866–872PubMedPubMedCentralGoogle Scholar
  28. Navarro X, Vivó M, Valero-Cabré A (2007) Neural plasticity after peripheral nerve injury and regeneration. Prog Neurobiol 82(4):163–201PubMedGoogle Scholar
  29. Nijhuis TH, Bodar CW, van Neck JW, Walbeehm ET, Siemionow M, Madajka M, Cwykiel J, Blok JH, Hovius SE (2013) Natural conduits for bridging a 15-mm nerve defect: comparison of the vein supported by muscle and bone marrow stromal cells with a nerve autograft. J Plast Reconstr Aesthet Surg 66(2):251–259PubMedGoogle Scholar
  30. Qin Y, Zhou C, Wang N, Yang H, Gao WQ (2015) Conversion of adipose tissue-derived mesenchymal stem cells to neural stem cell-like cells by a single transcription factor, Sox2. Cell Reprog 17(3):221–226Google Scholar
  31. Ren CL, Zhang ZY, Li L, Zhang CS, Dang RS (2007) Isolation, culture and identification of neural tissue-committed stem cells from bone marrow. Chin J Anatomy 30(4):435–437,486. (Article in Chinese)Google Scholar
  32. Ren CL, Zhang ZY, Zhang CS, Liu F, Sun Y, Li R, Zhang X, Li L (2008) Rehabilitation of sciatic nerve injury by transplantation of engineered nerve based on neural tissue-committed stem cells derived from bone marrow. Chin J Anat 31(1):51–55. (Article in Chinese)Google Scholar
  33. Ren CL, Zhang ZY, Liu F, Zhang CS, Li L (2009) Reconstruction of engineered nerve by neural tissue-committed stem cells derived from bone marrow. Chin J Anat 32(1):86–89. (Article in Chinese)Google Scholar
  34. Ritfeld GJ, Nandoe Tewarie RD, Vajn K, Rahiem ST, Hurtado A, Wendell DF, Roos RA, Oudega M (2012) Bone marrow stromal cell-mediated tissue sparing enhances functional repair after spinal cord contusion in adult rats. Cell Transplant 21(7):1561–1575PubMedGoogle Scholar
  35. Sandner B, Ciatipis M, Motsch M, Soljanik I, Weidner N, Blesch A (2016) Limited functional effects of subacute syngeneic bone marrow stromal cell transplantation after rat spinal cord contusion injury. Cell Transplant 25(1):125–139PubMedGoogle Scholar
  36. Wang D, Liu XL, Zhu JK, Hu J, Jiang L, Zhang Y, Yang LM, Wang HG, Zhu QT, Yi JH, Xi TF (2010) Repairing large radial nerve defects by acellular nerve allografts seeded with autologous bone marrow stromal cells in a monkey model. J Neurotrauma 27(10):1935–1943PubMedGoogle Scholar
  37. Wang YZ, Plane JM, Jiang P, Zhou CJ, Deng W (2011) Concise review: quiescent and active states of endogenous adult neural stem cells: identification and characterization. Stem Cells 29(6):907–912PubMedPubMedCentralGoogle Scholar
  38. Xu W, Zhao Z, Zhao B, Wang Y, Peng J, Zhang L, Chen J, Lu S (2011) Effect of different number of bone marrow mesenchymal stem cells on growth of rat dorsal root ganglia in vitro. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 25(10):1245–1249. (Article in Chinese)PubMedGoogle Scholar
  39. Yang Z, Zhu L, Li F, Wang J, Wan H, Pan Y (2014) Bone marrow stromal cells as a therapeutic treatment for ischemic stroke. Neurosci Bull 30(3):524–534PubMedPubMedCentralGoogle Scholar
  40. Yu Z, Wu S, Liu Z, Lin H, Chen L, Yuan X, Zhang Z, Liu F, Zhang C (2015) Sonic hedgehog and retinoic Acid induce bone marrow-derived stem cells to differentiate into glutamatergic neural cells. J Immunoassay Immunochem 36(1):1–15PubMedGoogle Scholar
  41. Yu ZH, Xu N, Zhang NL, Wang ZQ, Ji PY, Xiong YL, Qu HL, Zhang LP, Zhao DM, Zhang CS (2017) Rat model of sensory neuron disease induced by pyridoxine. Chin J Anat 40(4):412–416. (Article in Chinese)Google Scholar
  42. Zaminy A, Shokrgozar MA, Sadeghi Y, Noroozian M, Heidari MH, Piryaei A (2013) Mesenchymal stem cells as an alternative for Schwann cells in rat spinal cord injury. Iran Biomed J 17(3):113–122PubMedPubMedCentralGoogle Scholar
  43. Zeng R, Wang LW, Hu ZB, Guo WT, Wei JS, Lin H, Sun X, Chen LX, Yang LJ (2011) Differentiation of human bone marrow mesenchymal stem cells into neuron-like cells in vitro. Spine (Phila Pa 1976) 36(13):997–1005Google Scholar
  44. Zeng X, Qiu XC, Ma YH, Duan JJ, Chen YF, Gu HY, Wang JM, Ling EA, Wu JL, Wu W, Zeng YS (2015) Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection. Biomaterials 53:184–201PubMedGoogle Scholar
  45. Zhang K, Liu Z, Li G, Lai BQ, Qin LN, Ding Y, Ruan JW, Zhang SX, Zeng S (2014) Electro-acupuncture promotes the survival and differentiation of transplanted bone marrow mesenchymal stem cells pre-induced with neurotrophin-3 and retinoic acid in gelatin sponge scaffold after rat spinal cord transection. Stem Cell Rev 10(4):612–625Google Scholar
  46. Zhang Y, Liang G, Liu L, Lu L, Liu J (2015) The experimental study on repair of noise-induced hearing loss in guinea pigs by bone marrow NTCSCs transplantation. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 29(17):1556–1560. (Article in Chinese)PubMedGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Human Anatomy, College of Basic Medical SciencesBinzhou Medical UniversityYantaiPeople’s Republic of China
  2. 2.Department of Human Anatomy, College of Basic Medical SciencesSecond Military Medical UniversityShanghaiPeople’s Republic of China
  3. 3.Department of GastroenterologyYantai Affiliated Hospital of Binzhou Medical UniversityYantaiPeople’s Republic of China

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