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

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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.

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References

  • Abraham R, Verfaillie CM (2012) Neural differentiation and support of neuroregeneration of non-neural adult stem cells. Prog Brain Res 201:17–34

    Article  PubMed  Google Scholar 

  • Ahmed S (2009) The culture of neural stem cells. J Cell Biochem 106(1):1–6

    Article  CAS  PubMed  Google Scholar 

  • Allodi I, Udina E, Navarro X (2012) Specificity of peripheral nerve regeneration: interactions at the axon level. Prog Neurobiol 98(1):16–37

    Article  CAS  PubMed  Google Scholar 

  • 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):54–71

    Article  PubMed  PubMed Central  Google Scholar 

  • Andressen C (2013) Neural stem cells: from neurobiology to clinical applications. Curr Pharm Biotechnol 14(1):20–28

    CAS  PubMed  Google Scholar 

  • 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):48–58

    Article  CAS  PubMed  Google Scholar 

  • 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):55–63

    Article  CAS  PubMed  Google Scholar 

  • García-García A, de Castillejo CL, Méndez-Ferrer S (2015) BMSCs and hematopoiesis. Immunol Lett 168(2):129–135

    Article  PubMed  CAS  Google Scholar 

  • 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 1059:65–77

    Article  PubMed  Google Scholar 

  • 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):332–341

    Article  CAS  PubMed  Google Scholar 

  • 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):77–88

    Article  CAS  PubMed  Google Scholar 

  • 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):3077–3089

    Article  CAS  PubMed  Google Scholar 

  • 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):372–382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoffman RM (2014) Nestin-expressing hair follicle-accessible pluripotent stem cells for nerve and spinal cord repair. Cells Tissues Organs 200(1):42–47

    Article  CAS  PubMed  Google Scholar 

  • 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 10:117

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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):2617–2629

    Article  CAS  PubMed  Google Scholar 

  • 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):288–293

    Article  CAS  PubMed  Google Scholar 

  • 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 2016:6768274

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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):645–657

    Article  PubMed  Google Scholar 

  • 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):4789–4794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):52–57

    Article  CAS  PubMed  Google Scholar 

  • 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):18–28

    Article  CAS  PubMed  Google Scholar 

  • 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):755–763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):1085–1095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mezey E (2011) The therapeutic potential of bone marrow-derived stromal cells. J Cell Biochem 112(10):2683–2687

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):265–278

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Najafzadeh N, Esmaeilzade B, Imcheh MD (2015) Hair follicle stem cells: in vitro and in vivo neural differentiation. World J Stem Cells 7(5):866–872

    Article  PubMed  PubMed Central  Google Scholar 

  • Navarro X, Vivó M, Valero-Cabré A (2007) Neural plasticity after peripheral nerve injury and regeneration. Prog Neurobiol 82(4):163–201

    Article  CAS  PubMed  Google Scholar 

  • 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):251–259

    Article  PubMed  Google Scholar 

  • 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):221–226

    Article  CAS  Google Scholar 

  • 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)

    CAS  Google Scholar 

  • 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 

  • 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)

    CAS  Google Scholar 

  • 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):1561–1575

    Article  PubMed  Google Scholar 

  • 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):125–139

    Article  PubMed  Google Scholar 

  • 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):1935–1943

    Article  PubMed  Google Scholar 

  • 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):907–912

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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)

    PubMed  Google Scholar 

  • 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):524–534

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • 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):1–15

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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):113–122

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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):997–1005

    Article  Google Scholar 

  • 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 53:184–201

    Article  CAS  PubMed  Google Scholar 

  • 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):612–625

    Article  CAS  Google Scholar 

  • 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)

    PubMed  Google Scholar 

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Acknowledgements

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

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Author notes

  1. Zhenhai Yu, Ning Xu and Naili Zhang contributed to the work equally and should be considered as co-first authors.

Authors and Affiliations

  1. Department of Human Anatomy, College of Basic Medical Sciences, Binzhou Medical University, Yantai, 264003, People’s Republic of China

    Zhenhai Yu, Naili Zhang, Yanlian Xiong, Zhiqiang Wang, Shaohua Liang, Dongmei Zhao, Fei Huang & Chuansen Zhang

  2. Department of Human Anatomy, College of Basic Medical Sciences, Second Military Medical University, Shanghai, 200433, People’s Republic of China

    Zhenhai Yu & Chuansen Zhang

  3. Department of Gastroenterology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, 264100, People’s Republic of China

    Ning Xu

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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.

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Correspondence to Fei Huang or Chuansen Zhang.

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Yu, Z., Xu, N., Zhang, N. et al. Repair of Peripheral Nerve Sensory Impairments via the Transplantation of Bone Marrow Neural Tissue-Committed Stem Cell-Derived Sensory Neurons. Cell Mol Neurobiol 39, 341–353 (2019). https://doi.org/10.1007/s10571-019-00650-2

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