Skip to main content
SpringerLink
Log in

Ultrasound-Microbubble Transplantation of Bone Marrow Stromal Cells Improves Neurological Function after Forebrain Ischemia in Adult Mice

  • Original Paper
  • Published:
Cell Biochemistry and Biophysics Aims and scope Submit manuscript

Abstract

In this study, bone marrow stromal cells (MSCs) were transplanted into the brain of adult rats after forebrain ischemia induced by 4VO. SD rats (n = 60) were randomly divided into three groups: (I) rats (n = 20) were subjected to 4VO and transplanted with MSCs into the ischemic region using ultrasound-microbubble method, (2) rats (n = 20) were subjected to 4VO and transplanted with MSCs into the ischemic region (n = 20), and (3) 4VO alone (n = 20). Rats were sacrificed 28 days after treatment. Neurological functions of rats were evaluated by Morris Water Maze. The current findings suggest that the ultrasound microbubble transplanted MSCs survived in the ischemic brain and significantly improved functional recovery of adult rats compared to regular transplantation.

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

Similar content being viewed by others

References

  1. Studer, L., Tabar, V., & McKay, R. D. (1998). Transplantation of expanded mesencephalic precursors leads to recovery in parkinsonian rats. Nature Neuroscience, 1(4), 290–295.

    Article  CAS  PubMed  Google Scholar 

  2. Snyder, E. Y., Deitcher, D. L., Walsh, C., Arnold-Aldea, S., Hartwieg, E. A., & Cepko, C. L. (1992). Multipotent neural cell lines can engraft and participate in development of mouse cerebellum. Cell, 68(1), 33–51.

    Article  CAS  PubMed  Google Scholar 

  3. Lundberg, C., Field, P. M., Ajayi, Y. O., Raisman, G., & Bjorklund, A. (1996). Conditionally immortalized neural progenitor cell lines integrate and differentiate after grafting to the adult rat striatum. A combined autoradiographic and electron microscopic study. Brain Research, 737(1–2), 295–300.

    Article  CAS  PubMed  Google Scholar 

  4. Grabowski, M., Brundin, P., & Johansson, B. B. (1992). Fetal neocortical grafts implanted in adult hypertensive rats with cortical infarcts following a middle cerebral artery occlusion: ingrowth of afferent fibers from the host brain. Experimental Neurology, 116(2), 105–121.

    Article  CAS  PubMed  Google Scholar 

  5. Grabowski, M., Brundin, P., & Johansson, B. B. (1993). Functional integration of cortical grafts placed in brain infarcts of rats. Annals of neurology, 34(3), 362–368.

    Article  CAS  PubMed  Google Scholar 

  6. Defer, G. L., Geny, C., Ricolfi, F., Fenelon, G., Monfort, J. C., Remy, P., et al. (1996). Long-term outcome of unilaterally transplanted parkinsonian patients. I. Clinical approach. Brain: A Journal of Neurology, 119(Pt 1), 41–50.

    Article  Google Scholar 

  7. Kordower, J. H., Freeman, T. B., Snow, B. J., Vingerhoets, F. J., Mufson, E. J., Sanberg, P. R., et al. (1995). Neuropathological evidence of graft survival and striatal reinnervation after the transplantation of fetal mesencephalic tissue in a patient with Parkinson’s disease. The New England Journal of Medicine, 332(17), 1118–1124.

    Article  CAS  PubMed  Google Scholar 

  8. Jansen, E. M., Solberg, L., Underhill, S., Wilson, S., Cozzari, C., Hartman, B. K., et al. (1997). Transplantation of fetal neocortex ameliorates sensorimotor and locomotor deficits following neonatal ischemic-hypoxic brain injury in rats. Experimental Neurology, 147(2), 487–497.

    Article  CAS  PubMed  Google Scholar 

  9. Borlongan, C. V., Tajima, Y., Trojanowski, J. Q., Lee, V. M., & Sanberg, P. R. (1998). Cerebral ischemia and CNS transplantation: differential effects of grafted fetal rat striatal cells and human neurons derived from a clonal cell line. NeuroReport, 9(16), 3703–3709.

    Article  CAS  PubMed  Google Scholar 

  10. Eglitis, M. A., Dawson, D., Park, K. W., & Mouradian, M. M. (1999). Targeting of marrow-derived astrocytes to the ischemic brain. NeuroReport, 10(6), 1289–1292.

    Article  CAS  PubMed  Google Scholar 

  11. Chen, J., Li, Y., & Chopp, M. (2000). Intracerebral transplantation of bone marrow with BDNF after MCAo in rat. Neuropharmacology, 39(5), 711–716.

    Article  CAS  PubMed  Google Scholar 

  12. Karlsson, S. (1991). Treatment of genetic defects in hematopoietic cell function by gene transfer. Blood, 78(10), 2481–2492.

    CAS  PubMed  Google Scholar 

  13. Walsh, C. E., Nienhuis, A. W., Samulski, R. J., Brown, M. G., Miller, J. L., Young, N. S., et al. (1994). Phenotypic correction of Fanconi anemia in human hematopoietic cells with a recombinant adeno-associated virus vector. The Journal of Clinical Investigation, 94(4), 1440–1448.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Prockop, D. J. (1997). Marrow stromal cells as stem cells for nonhematopoietic tissues. Science, 276(5309), 71–74.

    Article  CAS  PubMed  Google Scholar 

  15. Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., et al. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284(5411), 143–147.

    Article  CAS  PubMed  Google Scholar 

  16. Bruder, S. P., Jaiswal, N., Ricalton, N. S., Mosca, J. D., Kraus, K. H., & Kadiyala, S. (1998). Mesenchymal stem cells in osteobiology and applied bone regeneration. Clinical Orthopaedics and Related Research, 355, 247–256.

    Article  Google Scholar 

  17. Colter, D. C., Class, R., DiGirolamo, C. M., & Prockop, D. J. (2000). Rapid expansion of recycling stem cells in cultures of plastic-adherent cells from human bone marrow. Proceedings of the National Academy of Sciences of the United States of America, 97(7), 3213–3218.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Horwitz, E. M., Prockop, D. J., Fitzpatrick, L. A., Koo, W. W., Gordon, P. L., Neel, M., et al. (1999). Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nature Medicine, 5(3), 309–313.

    Article  CAS  PubMed  Google Scholar 

  19. Mason, J. M., Grande, D. A., Barcia, M., Grant, R., Pergolizzi, R. G., & Breitbart, A. S. (1998). Expression of human bone morphogenic protein 7 in primary rabbit periosteal cells: potential utility in gene therapy for osteochondral repair. Gene Therapy, 5(8), 1098–1104.

    Article  CAS  PubMed  Google Scholar 

  20. Black, I. B., & Woodbury, D. (2001). Adult rat and human bone marrow stromal stem cells differentiate into neurons. Blood Cells, Molecules, & Diseases, 27(3), 632–636.

    Article  CAS  Google Scholar 

  21. Eglitis, M. A., & Mezey, E. (1997). Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proceedings of the National Academy of Sciences of the United States of America, 94(8), 4080–4085.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Li, Y., Chopp, M., Chen, J., Wang, L., Gautam, S. C., Xu, Y. X., et al. (2000). Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. Journal of cerebral blood flow and metabolism: Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 20(9), 1311–1319.

    Article  CAS  Google Scholar 

  23. Kopen, G. C., Prockop, D. J., & Phinney, D. G. (1999). Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proceedings of the National Academy of Sciences of the United States of America, 96(19), 10711–10716.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Chen, J., Li, Y., Wang, L., Zhang, Z., Lu, D., Lu, M., et al. (2001). Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke: A Journal of Cerebral Circulation, 32(4), 1005–1011.

    Article  CAS  Google Scholar 

  25. Li, Y., Chen, J., Wang, L., Lu, M., & Chopp, M. (2001). Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology, 56(12), 1666–1672.

    Article  CAS  PubMed  Google Scholar 

  26. Zhao, L. R., Duan, W. M., Reyes, M., Keene, C. D., Verfaillie, C. M., & Low, W. C. (2002). Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Experimental Neurology, 174(1), 11–20.

    Article  PubMed  Google Scholar 

  27. Chen, J., Li, Y., Wang, L., Lu, M., Zhang, X., & Chopp, M. (2001). Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. Journal of the Neurological Sciences, 189(1–2), 49–57.

    Article  CAS  PubMed  Google Scholar 

  28. Pulsinelli, W. A., & Buchan, A. M. (1988). The four-vessel occlusion rat model: method for complete occlusion of vertebral arteries and control of collateral circulation. Stroke: A Journal of Cerebral Circulation, 19(7), 913–914.

    Article  CAS  Google Scholar 

  29. Pulsinelli, W. A., Levy, D. E., & Duffy, T. E. (1982). Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia. Annals of Neurology, 11(5), 499–502.

    Article  CAS  PubMed  Google Scholar 

  30. Chu, P. C., Chai, W. Y., Hsieh, H. Y., Wang, J. J., Wey, S. P., Huang, C. Y., et al. (2013). Pharmacodynamic analysis of magnetic resonance imaging-monitored focused ultrasound-induced blood-brain barrier opening for drug delivery to brain tumors. BioMed Research International, 2013, 627496.

    PubMed Central  PubMed  Google Scholar 

  31. Goto, S., Yamada, K., Yoshikawa, M., Okamura, A., & Ushio, Y. (1997). GABA receptor agonist promotes reformation of the striatonigral pathway by transplant derived from fetal striatal primordia in the lesioned striatum. Experimental Neurology, 147(2), 503–509.

    Article  CAS  PubMed  Google Scholar 

  32. Morris, R. (1984). Developments of a water-maze procedure for studying spatial learning in the rat. Journal of Neuroscience Methods, 11(1), 47–60.

    Article  CAS  PubMed  Google Scholar 

  33. Morris, R. G., Garrud, P., Rawlins, J. N., & O’Keefe, J. (1982). Place navigation impaired in rats with hippocampal lesions. Nature, 297(5868), 681–683.

    Article  CAS  PubMed  Google Scholar 

  34. Li, Y., Chen, J., Chen, X. G., Wang, L., Gautam, S. C., Xu, Y. X., et al. (2002). Human marrow stromal cell therapy for stroke in rat: neurotrophins and functional recovery. Neurology, 59(4), 514–523.

    Article  CAS  PubMed  Google Scholar 

  35. Berezovskaya, O., Maysinger, D., & Fedoroff, S. (1996). Colony stimulating factor-1 potentiates neuronal survival in cerebral cortex ischemic lesion. Acta Neuropathologica, 92(5), 479–486.

    Article  CAS  PubMed  Google Scholar 

  36. Maestroni, G. J., Cosentino, M., Marino, F., Togni, M., Conti, A., Lecchini, S., et al. (1998). Neural and endogenous catecholamines in the bone marrow. Circadian association of norepinephrine with hematopoiesis? Experimental Hematology, 26(12), 1172–1177.

    CAS  PubMed  Google Scholar 

  37. Chen, X., Li, Y., Wang, L., Katakowski, M., Zhang, L., Chen, J., et al. (2002). Ischemic rat brain extracts induce human marrow stromal cell growth factor production. Neuropathology: Official Journal of the Japanese Society of Neuropathology, 22(4), 275–279.

    Article  Google Scholar 

  38. Lindholm, D. (1997). Neurotrophic factors and neuronal plasticity: is there a link? Advances in Neurology, 73, 1–6.

    CAS  PubMed  Google Scholar 

  39. Hess, D. C., Hill, W. D., Martin-Studdard, A., Carroll, J., Brailer, J., & Carothers, J. (2002). Bone marrow as a source of endothelial cells and NeuN-expressing cells After stroke. Stroke; A Journal of Cerebral Circulation, 33(5), 1362–1368.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by Chongqing Natural science Foundation CSTC201JJA10011, National Natural Science Foundation Nos. 81271331 and 81000507.

Author information

Authors and Affiliations

  1. Department of Neurology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400000, China

    Zili Gong, Hong Ran & Jian Zheng

  2. Department of Ultrasound, Xinqiao Hospital, Third Military Medical University, Chongqi, China

    Shengzheng Wu

  3. Department of Neurology, Daping Hospital, Third Military Medical University, Chongqi, China

    Jie Zhu

Authors
  1. Zili Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hong Ran
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shengzheng Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jian Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jian Zheng.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gong, Z., Ran, H., Wu, S. et al. Ultrasound-Microbubble Transplantation of Bone Marrow Stromal Cells Improves Neurological Function after Forebrain Ischemia in Adult Mice. Cell Biochem Biophys 70, 499–504 (2014). https://doi.org/10.1007/s12013-014-9947-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12013-014-9947-y

Keywords

Search

Navigation