Skip to main content

Advertisement

SpringerLink
Log in

Comparison of Transdifferentiated and Untransdifferentiated Human Umbilical Mesenchymal Stem Cells in Rats after Traumatic Brain Injury

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Transdifferentiated and untransdifferentiated mesenchymal stem cells (MSCs) have shown therapeutic benefits in central nervous system (CNS) injury. However, it is unclear which would be more appropriate for transplantation. To address this question, we transplanted untransdifferentiated human umbilical mesenchymal stem cells (HUMSCs) and transdifferentiated HUMSCs (HUMSC-derived neurospheres, HUMSC-NSs) into a rat model of traumatic brain injury. Cognitive function, cell survival and differentiation, brain tissue morphology and neurotrophin expression were compared between groups. Significant improvements in cognitive function and brain tissue morphology were seen in the HUMSCs group compared with HUMSC-NSs group, which was accompanied by increased neurotrophin expression. Moreover, only few grafted cells survived in both the HUMSCs and HUMSC-NSs groups, with very few of the cells differentiating into neural-like cells. These findings indicate that HUMSCs are more appropriate for transplantation and their therapeutic benefits may be associated with neuroprotection rather than cell replacement.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Bruns JJ, Hauser WA (2003) The epidemiology of traumatic brain injury: a review. Epilepsia 44(Suppl 10):2–10

    Article  PubMed  Google Scholar 

  2. Walker PA, Jimenez F, Cox CJ (2010) Progenitor cell therapy for traumatic brain injury: effect of serum osmolarity on cell viability and cytokine production. Regen Med 5:65–71

    Article  PubMed  CAS  Google Scholar 

  3. Skardelly M, Gaber K, Burdack S et al (2011) Long-term benefit of human fetal neuronal progenitor cell transplantation in a clinically adapted model after traumatic brain injury. J Neurotrauma 28:401–414

    Article  PubMed  Google Scholar 

  4. Gao J, Prough DS, McAdoo DJ et al (2006) Transplantation of primed human fetal neural stem cells improves cognitive function in rats after traumatic brain injury. Exp Neurol 201:281–292

    Article  PubMed  CAS  Google Scholar 

  5. Gogel S, Gubernator M, Minger SL (2011) Progress and prospects: stem cells and neurological diseases. Gene Ther 18:1–6

    Article  PubMed  CAS  Google Scholar 

  6. Walker PA, Shah SK, Harting MT et al (2009) Progenitor cell therapies for traumatic brain injury: barriers and opportunities in translation. Dis Model Mech 2:23–38

    Article  PubMed  CAS  Google Scholar 

  7. Lee MW, Moon YJ, Yang MS et al (2007) Neural differentiation of novel multipotent progenitor cells from cryopreserved human umbilical cord blood. Biochem Biophys Res Commun 358:637–643

    Article  PubMed  CAS  Google Scholar 

  8. Vaquero J, Zurita M (2009) Bone marrow stromal cells for spinal cord repair: a challenge for contemporary neurobiology. Histol Histopathol 24:107–116

    PubMed  CAS  Google Scholar 

  9. Zhang L, Zhang HT, Hong SQ et al (2009) Cografted Wharton’s jelly cells-derived neurospheres and BDNF promote functional recovery after rat spinal cord transection. Neurochem Res 34:2030–2039

    Article  PubMed  CAS  Google Scholar 

  10. Fu YS, Cheng YC, Lin MY et al (2006) Conversion of human umbilical cord mesenchymal stem cells in Wharton’s jelly to dopaminergic neurons in vitro: potential therapeutic application for Parkinsonism. Stem Cells 24:115–124

    Article  PubMed  Google Scholar 

  11. Kim HJ, Lee JH, Kim SH (2010) Therapeutic effects of human mesenchymal stem cells on traumatic brain injury in rats: secretion of neurotrophic factors and inhibition of apoptosis. J Neurotrauma 27:131–138

    Article  PubMed  Google Scholar 

  12. Koh SH, Kim KS, Choi MR et al (2008) Implantation of human umbilical cord-derived mesenchymal stem cells as a neuroprotective therapy for ischemic stroke in rats. Brain Res 1229:233–248

    Article  PubMed  CAS  Google Scholar 

  13. Hermann A, Gastl R, Liebau S et al (2004) Efficient generation of neural stem cell-like cells from adult human bone marrow stromal cells. J Cell Sci 117:4411–4422

    Article  PubMed  CAS  Google Scholar 

  14. Zhang HT, Cheng HY, Cai YQ et al (2009) Comparison of adult neurospheres derived from different origins for treatment of rat spinal cord injury. Neurosci Lett 458:116–121

    Article  PubMed  CAS  Google Scholar 

  15. Feeney DM, Boyeson MG, Linn RT et al (1981) Responses to cortical injury: I. Methodology and local effects of contusions in the rat. Brain Res 211:67–77

    Article  PubMed  CAS  Google Scholar 

  16. Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates coordinates, 5th edn. Elsevier Academic Press, San Diego, pp 98–123

    Google Scholar 

  17. Hains BC, Saab CY, Lo AC et al (2004) Sodium channel blockade with phenytoin protects spinal cord axons, enhances axonal conduction, and improves functional motor recovery after contusion SCI. Exp Neurol 188:365–377

    Article  PubMed  CAS  Google Scholar 

  18. ABERCROMBIE M (1946) Estimation of nuclear population from microtome sections. Anat Rec 94:239–247

    Article  PubMed  CAS  Google Scholar 

  19. Liao W, Xie J, Zhong J et al (2009) Therapeutic effect of human umbilical cord multipotent mesenchymal stromal cells in a rat model of stroke. Transplantation 87:350–359

    Article  PubMed  Google Scholar 

  20. Weiss ML, Medicetty S, Bledsoe AR et al (2006) Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells 24:781–792

    Article  PubMed  CAS  Google Scholar 

  21. Zurita M, Bonilla C, Otero L et al (2008) Neural transdifferentiation of bone marrow stromal cells obtained by chemical agents is a short-time reversible phenomenon. Neurosci Res 60:275–280

    Article  PubMed  CAS  Google Scholar 

  22. Yang CC, Shih YH, Ko MH et al (2008) Transplantation of human umbilical mesenchymal stem cells from Wharton’s jelly after complete transection of the rat spinal cord. PLoS One 3:e3336

    Article  PubMed  Google Scholar 

  23. Boyce VS, Tumolo M, Fischer I et al (2007) Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats. J Neurophysiol 98:1988–1996

    Article  PubMed  Google Scholar 

  24. Zhang W, Yan Q, Zeng YS et al (2010) Implantation of adult bone marrow-derived mesenchymal stem cells transfected with the neurotrophin-3 gene and pretreated with retinoic acid in completely transected spinal cord. Brain Res 1359:256–271

    Article  PubMed  CAS  Google Scholar 

  25. Shang AJ, Hong SQ, Xu Q et al (2011) NT-3-secreting human umbilical cord mesenchymal stromal cell transplantation for the treatment of acute spinal cord injury in rats. Brain Res 1391:102–113

    Article  PubMed  CAS  Google Scholar 

  26. Bath KG, Lee FS (2006) Variant BDNF (Val66Met) impact on brain structure and function. Cogn Affect Behav Neurosci 6:79–85

    Article  PubMed  Google Scholar 

  27. Pisati F, Bossolasco P, Meregalli M et al (2007) Induction of neurotrophin expression via human adult mesenchymal stem cells: implication for cell therapy in neurodegenerative diseases. Cell Transplant 16:41–55

    PubMed  Google Scholar 

  28. Hayase M, Kitada M, Wakao S et al (2009) Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke. J Cereb Blood Flow Metab 29:1409–1420

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors acknowledge Health & Biotech Company (Guangzhou, Guangdong, China) for them kindly present human umbilical mesenchymal stem cells. This work was supported by Natural Science Foundation of China (NSFC) (No. U0632008, 30772232, 30801184) and Foundation for Key Sci-Tech Research Projects of Guangdong (No. 2008A030201019, 2007-05/06-70052).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China

    Sun-Quan Hong, Jian You, Mao-Ying Zhang, Ying-Qian Cai, Xiao-Dan Jiang & Ru-Xiang Xu

  2. Institute of Neurosurgery, Key Laboratory on Brain Function Repair and Regeneration of Guangdong, Southern Medical University, Guangzhou, 510282, China

    Sun-Quan Hong, Jian You, Mao-Ying Zhang, Ying-Qian Cai, Xiao-Dan Jiang & Ru-Xiang Xu

  3. Department of Neurosurgery, The Military General Hospital of Beijing PLA, Beijing, 100700, China

    Sun-Quan Hong, Hong-Tian Zhang & Ru-Xiang Xu

Authors
  1. Sun-Quan Hong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong-Tian Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian You
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mao-Ying Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying-Qian Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiao-Dan Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ru-Xiang Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Xiao-Dan Jiang or Ru-Xiang Xu.

Additional information

Hong-Tian Zhang contributed equally with the first author.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hong, SQ., Zhang, HT., You, J. et al. Comparison of Transdifferentiated and Untransdifferentiated Human Umbilical Mesenchymal Stem Cells in Rats after Traumatic Brain Injury. Neurochem Res 36, 2391–2400 (2011). https://doi.org/10.1007/s11064-011-0567-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-011-0567-2

Keywords

Search

Navigation