Skip to main content
SpringerLink
Log in

Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function

  • Cover Article
  • Published:
Science China Life Sciences Aims and scope Submit manuscript

Abstract

Grafted embryonic central neural tissue pieces can recover function of hemisected spinal cord in neonatal rats and promote axonal growth in adults. However, spinal cord segments from adults have not been used as donor segments for allogeneic transplantation. Here, we utilized adult spinal cord tissue grafts (aSCGs) as donor constructs for repairing complete spinal cord injury (SCI). Moreover, to provide a favourable microenvironment for SCI treatment, a growth factor cocktail containing three growth factors (brain-derived neurotrophic factor, neurotrophin-3 and vascular endothelial growth factor), was applied to the aSCG transplants. We found that the locomotor function was significantly improved 12 weeks after transplantation of aSCGs into the spinal cord lesion site in adult rats. Transplantation of aSCGs combined with these growth factors enhanced neuron and oligodendrocyte survival and functional restoration. These encouraging results indicate that treatment of complete SCI by transplanting aSCGs, especially in the presence of growth factors, has a positive effect on motor functional recovery, and therefore could be considered as a possible therapeutic strategy for SCI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bramlett, H.M., and Dietrich, W.D. (2007). Progressive damage after brain and spinal cord injury: pathomechanisms and treatment strategies. Prog Brain Res 161, 125–141.

    Article  PubMed  Google Scholar 

  • Chen, X., Zhao, Y., Li, X., Xiao, Z., Yao, Y., Chu, Y., Farkas, B., Romano, I., Brandi, F., and Dai, J. (2018). Functional multichannel poly (propylene fumarate)-collagen scaffold with collagen-binding neurotrophic factor 3 promotes neural regeneration after transected spinal cord injury. Adv Healthcare Mater 7, 1800315.

    Article  CAS  Google Scholar 

  • Collier, T.J., Sortwell, C.E., and Daley, B.F. (1999). Diminished viability, growth, and behavioral efficacy of fetal dopamine neuron grafts in aging rats with long-term dopamine depletion: an argument for neurotrophic supplementation. J Neurosci 19, 5563–5573.

    Article  CAS  PubMed  Google Scholar 

  • des Rieux, A., De Berdt, P., Ansorena, E., Ucakar, B., Damien, J., Schakman, O., Audouard, E., Bouzin, C., Auhl, D., Simón-Yarza, T., et al. (2014). Vascular endothelial growth factor-loaded injectable hydrogel enhances plasticity in the injured spinal cord. J Biomed Mater Res 102, 2345–2355.

    Article  CAS  Google Scholar 

  • Fan, C., Li, X., Zhao, Y., Xiao, Z., Xue, W., Sun, J., Li, X., Zhuang, Y., Chen, Y., and Dai, J. (2018). Cetuximab and Taxol co-modified collagen scaffolds show combination effects for the repair of acute spinal cord injury. Biomater Sci 6, 1723–1734.

    Article  CAS  PubMed  Google Scholar 

  • Fan, J., Xiao, Z., Zhang, H., Chen, B., Tang, G., Hou, X., Ding, W., Wang, B., Zhang, P., Dai, J., et al. (2010). Linear ordered collagen scaffolds loaded with collagen-binding neurotrophin-3 promote axonal regeneration and partial functional recovery after complete spinal cord transection. J Neurotrauma 27, 1671–1683.

    Article  PubMed  Google Scholar 

  • Gaillard, F., and Sauve, Y. (1995). Fetal tissue allografts in the central visual system of rodents. In Webvision: The Organization of the Retina and Visual System (University of Utah Health Sciences Center).

    Google Scholar 

  • Hallas, B.H., Das, G.D., and Das, K.G. (1980). Transplantation of brain tissue in the brain of rat. II. Growth characteristics of neocortical transplants in hosts of different ages. Am J Anat 158, 147–159.

    Article  CAS  PubMed  Google Scholar 

  • Han, J., and Dai, J. (2016). Microgravity may help future organ/tissue manufacture. Sci China Life Sci 59, 850–853.

    Article  PubMed  Google Scholar 

  • Han, Q., Sun, W., Lin, H., Zhao, W., Gao, Y., Zhao, Y., Chen, B., Xiao, Z., Hu, W., Li, Y., et al. (2009). Linear ordered collagen scaffolds loaded with collagen-binding brain-derived neurotrophic factor improve the recovery of spinal cord injury in rats. Tissue Eng Part A 15, 2927–2935.

    Article  CAS  PubMed  Google Scholar 

  • Han, S., Li, X., Xiao, Z., and Dai, J. (2018a). Complete canine spinal cord transection model: a large animal model for the translational research of spinal cord regeneration. Sci China Life Sci 61, 115–117.

    Article  PubMed  Google Scholar 

  • Han, S., Wang, B., Jin, W., Xiao, Z., Chen, B., Xiao, H., Ding, W., Cao, J., Ma, F., Li, X., et al. (2014). The collagen scaffold with collagen binding BDNF enhances functional recovery by facilitating peripheral nerve infiltrating and ingrowth in canine complete spinal cord transection. Spinal Cord 52, 867–873.

    Article  CAS  PubMed  Google Scholar 

  • Han, S., Xiao, Z., Li, X., Zhao, H., Wang, B., Qiu, Z., Li, Z., Mei, X., Xu, B., Fan, C., et al. (2018b). Human placenta-derived mesenchymal stem cells loaded on linear ordered collagen scaffold improves functional recovery after completely transected spinal cord injury in canine. Sci China Life Sci 61, 2–13.

    Article  CAS  PubMed  Google Scholar 

  • Horvat, J.C. (1991). Transplants of fetal neural tissue and autologous peripheral nerves in an attempt to repair spinal cord injuries in the adult rat. An overall view. Paraplegia 29, 299–308.

    CAS  PubMed  Google Scholar 

  • Iwashita, Y., Kawaguchi, S., and Murata, M. (1994). Restoration of function by replacement of spinal cord segments in the rat. Nature 367, 167–170.

    Article  CAS  PubMed  Google Scholar 

  • Jakeman, L.B., and Reier, P.J. (1991). Axonal projections between fetal spinal cord transplants and the adult rat spinal cord: a neuroanatomical tracing study of local interactions. J Comp Neurol 307, 311–334.

    Article  CAS  PubMed  Google Scholar 

  • Kucharova, K., and Stallcup, W.B. (2010). The NG2 proteoglycan promotes oligodendrocyte progenitor proliferation and developmental myelination. Neuroscience 166, 185–194.

    Article  CAS  Google Scholar 

  • Lee, B.B., Cripps, R.A., Fitzharris, M., and Wing, P.C. (2014). The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal Cord 52, 110–116.

    Article  CAS  PubMed  Google Scholar 

  • Lee, Y.S., Lin, C.Y., Jiang, H.H., DePaul, M., Lin, V.W., and Silver, J. (2013). Nerve regeneration restores supraspinal control of bladder function after complete spinal cord injury. J Neurosci 33, 10591–10606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, J., Chen, S., Zhao, Z., Luo, Y., Hou, Y., Li, H., He, L., Zhou, L., and Wu, W. (2017a). Effect of VEGF on inflammatory regulation, neural survival, and functional improvement in rats following a complete spinal cord transection. Front Cell Neurosci 11, 381.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, X., and Dai, J. (2018). Bridging the gap with functional collagen scaffolds: tuning endogenous neural stem cells for severe spinal cord injury repair. Biomater Sci 6, 265–271.

    Article  CAS  PubMed  Google Scholar 

  • Li, X., Han, J., Zhao, Y., Ding, W., Wei, J., Li, J., Han, S., Shang, X., Wang, B., Chen, B., et al. (2016a). Functionalized collagen scaffold implantation and cAMP administration collectively facilitate spinal cord regeneration. Acta Biomater 30, 233–245.

    Article  CAS  PubMed  Google Scholar 

  • Li, X., Liu, S., Zhao, Y., Li, J., Ding, W., Han, S., Chen, B., Xiao, Z., and Dai, J. (2016b). Training neural stem cells on functional collagen scaffolds for severe spinal cord injury repair. Adv Funct Mater 26, 5835–5847.

    Article  CAS  Google Scholar 

  • Li, X., Zhao, Y., Cheng, S., Han, S., Shu, M., Chen, B., Chen, X., Tang, F., Wang, N., Tu, Y., et al. (2017b). Cetuximab modified collagen scaffold directs neurogenesis of injury-activated endogenous neural stem cells for acute spinal cord injury repair. Biomaterials 137, 73–86.

    Article  CAS  PubMed  Google Scholar 

  • Liu, S.M., Xiao, Z.F., Li, X., Zhao, Y.N., Wu, X.M., Han, J., Chen, B., Li, J. Y., Fan, C.X., Xu, B., et al. (2019). Vascular endothelial growth factor activates neural stem cells through epidermal growth factor receptor signal after spinal cord injury. CNS Neurosci Ther 25, 375–385.

    Article  CAS  PubMed  Google Scholar 

  • Maier, I.C., and Schwab, M.E. (2006). Sprouting, regeneration and circuit formation in the injured spinal cord: factors and activity. Philos Trans R Soc B-Biol Sci 361, 1611–1634.

    Article  CAS  Google Scholar 

  • McTigue, D.M., Horner, P.J., Stokes, B.T., and Gage, F.H. (1998). Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. J Neurosci 18, 5354–5365.

    Article  CAS  PubMed  Google Scholar 

  • Mobley, P., and Greengard, P. (1985). Evidence for widespread effects of noradrenaline on axon terminals in the rat frontal cortex.. Proc Natl Acad Sci USA 82, 945–947.

    Article  CAS  PubMed  Google Scholar 

  • Palmer, T.D., Willhoite, A.R., and Gage, F.H. (2000). Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425, 479–494.

    Article  CAS  Google Scholar 

  • Reier, P.J., Bregman, B.S., and Wujek, J.R. (1986). Intraspinal transplantation of embyronic spinal cord tissue in neonatal and adult rats. J Comp Neurol 247, 275–296.

    Article  CAS  Google Scholar 

  • Shi, Q., Gao, W., Han, X.L., Zhu, X.S., Sun, J., Xie, F., Hou, X.L., Yang, H. L., Dai, J.W., and Chen, L. (2014). Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in a rat hemisected spinal cord injury model. Sci China Life Sci 57, 232–240.

    Article  CAS  PubMed  Google Scholar 

  • Sirko, S., Irmler, M., Gascón, S., Bek, S., Schneider, S., Dimou, L., Obermann, J., De Souza Paiva, D., Poirier, F., Beckers, J., et al. (2015). Astrocyte reactivity after brain injury: The role of galectins 1 and 3. Glia 63, 2340–2361.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sondell, M., Lundborg, G., and Kanje, M. (1999). Vascular endothelial growth factor has neurotrophic activity and stimulates axonal outgrowth, enhancing cell survival and Schwann cell proliferation in the peripheral nervous system. J Neurosci 19, 5731–5740.

    Article  CAS  PubMed  Google Scholar 

  • Spencer, T., Domeniconi, M., Cao, Z., and Filbin, M.T. (2003). New roles for old proteins in adult CNS axonal regeneration. Curr Opin Neurobiol 13, 133–139.

    Article  CAS  PubMed  Google Scholar 

  • Tsai, E.C., Krassioukov, A.V., and Tator, C.H. (2005). Corticospinal regeneration into lumbar grey matter correlates with locomotor recovery after complete spinal cord transection and repair with peripheral nerve grafts, fibroblast growth factor 1, fibrin glue, and spinal fusion. J Neuropathol Exp Neurol 64, 230–244.

    Article  PubMed  Google Scholar 

  • Wang, L., Shi, Q., Dai, J., Gu, Y., Feng, Y., and Chen, L. (2018). Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor-targeting collagen scaffold. J Orthop Res 36, 1024–1034.

    CAS  PubMed  Google Scholar 

  • Widenfalk, J., Lipson, A., Jubran, M., Hofstetter, C., Ebendal, T., Cao, Y., and Olson, L. (2003). Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury. Neuroscience 120, 951–960.

    Article  CAS  PubMed  Google Scholar 

  • Xiao, Z., Tang, F., Tang, J., Yang, H., Zhao, Y., Chen, B., Han, S., Wang, N., Li, X., Cheng, S., et al. (2016). One-year clinical study of NeuroRegen scaffold implantation following scar resection in complete chronic spinal cord injury patients. Sci China Life Sci 59, 647–655.

    Article  CAS  PubMed  Google Scholar 

  • Xu, Z., Han, K., Chen, J., Wang, C., Dong, Y., Yu, M., Bai, R., Huang, C., and Hou, L. (2017a). Vascular endothelial growth factor is neuroprotective against ischemic brain injury by inhibiting scavenger receptor A expression on microglia. J Neurochem 142, 700–709.

    Article  CAS  PubMed  Google Scholar 

  • Xu, Z.X., Zhang, L.Q., Wang, C.S., Chen, R.S., Li, G.S., Guo, Y., and Xu, W.H. (2017b). Acellular spinal cord scaffold implantation promotes vascular remodeling with sustained delivery of VEGF in a rat spinal cord hemisection model. Curr Neurovasc Res 14, 274–289.

    Article  CAS  PubMed  Google Scholar 

  • Zhang, J., Ding, L., Zhao, Y., Sun, W., Chen, B., Lin, H., Wang, X., Zhang, L., Xu, B., and Dai, J. (2009). Collagen-targeting vascular endothelial growth factor improves cardiac performance after myocardial infarction. Circulation 119, 1776–1784.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, Q., Li, Z.Y., Zhang, Z.P., Mo, Z.Y., Chen, S.J., Xiang, S.Y., Zhang, Q.S., and Xue, M. (2015). Polylactic-co-glycolic acid microspheres containing three neurotrophic factors promote sciatic nerve repair after injury. Neural Regen Res 10, 1491–1497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81891002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020100).

Author information

Author notes

  1. Contributed equally to this work

Authors and Affiliations

  1. Key Laboratory for Nano-Bio Interface Research, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou, 215123, China

    He Shen & Jianwu Dai

  2. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China

    Xing Li, Zhifeng Xiao & Jianwu Dai

  3. Shigatse Branch, Xinqiao Hospital, Army Medical University (Third Military Medical University), Shigatse, 857000, China

    Xi Chen & Ke Jia

  4. Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Xiangya Hospital, Central South University, Changsha, 410008, China

    Xing Li

Authors
  1. He Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xi Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xing Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ke Jia
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhifeng Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jianwu Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jianwu Dai.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shen, H., Chen, X., Li, X. et al. Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function. Sci. China Life Sci. 62, 725–733 (2019). https://doi.org/10.1007/s11427-019-9490-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11427-019-9490-8

Keywords

Search

Navigation