Abstract
To optimize a technique that induces bone marrow mesenchymal stem cells (BMSCs) to differentiation into neural-like cells, using cerebrospinal fluid (CSF) from the patient. In vitro, CSF (Group A) and the cell growth factors EGF and bFGF (Group B) were used to induce BMSCs to differentiate into neural-like cells. Post-induction, presence of neural-like cells was confirmed through the use of light and immunofluorescence microscopy. BMSCs can be induced to differentiate into neural-like cells. The presence of neural-like cells was confirmed via morphological characteristics, phenotype, and biological properties. Induction using CSF can shorten the production time of neural-like cells and the quantity is significantly higher than that obtained by induction with growth factor (P < 0.01). The two induction methods can induce BMSCs to differentiate into neural-like cells. Using CSF induction, 30 ml bone marrow can produce a sufficient number of neural-like cells that totally meet the requirements for clinical treatment.
Similar content being viewed by others
Change history
13 September 2023
An Editorial Expression of Concern to this paper has been published: https://doi.org/10.1007/s12013-023-01170-z
Abbreviations
- BMSCs:
-
Bone marrow mesenchymal stem cells
- CSF:
-
Cerebrospinal fluid
- auto-CSF:
-
Autologous cerebrospinal fluid
- CNS:
-
The central nervous system
- IMDM:
-
Iscove’s modified Dulbecco’s medium
- PBS:
-
Phosphate-buffered saline
- FBS:
-
Fetal bovine serum
References
Prockop, D. J., Gregory, C. A., & Spees, J. L. (2003). One strategy for cell and gene therapy: Harnessing the power of adult stem cells to repair tissues. Proceedings of the National Academy of Sciences USA, 100(Suppl. 1), 11917–11923.
de Vasconcelos Dos Santos, A., da Costa Reis, J., Diaz Paredes, B., Moraes, L., Jasmin Giraldi-Guimaraes, A., & Mendez-Otero, R. (2010). Therapeutic window for treatment of cortical ischemia with bone marrow-derived cells in rats. Brain Research, 1306, 149–158.
Hayase, M., Kitada, M., Wakao, S., Itokazu, Y., Nozaki, K., Hashimoto, N., et al. (2009). Committed neural progenitor cells derived from genetically modified bone marrow stromal cells ameliorate deficits in a rat model of stroke. Journal of Cerebral Blood Flow and Metabolism, 29, 1409–1420.
Lee, D. H., Ahn, Y., Kim, S. U., Wang, K. C., Cho, B. K., Phi, J. H., et al. (2009). Targeting rat brainstem glioma using human neural stem cells and human mesenchymal stem cells. Clinical Cancer Research, 15, 4925–4934.
Lee, J. K., Jin, H. K., & Bae, J. S. (2009). Bone marrow-derived mesenchymal stem cells reduce brain amyloid-beta deposition and accelerate the activation of microglia in an acutely induced Alzheimer’s disease mouse model. Neuroscience Letters, 450, 136–141.
Song, C. H., Honmou, O., Ohsawa, N., Nakamura, K., Hamada, H., Furuoka, H., et al. (2009). Effect of transplantation of bone marrow-derived mesenchymal stem cells on mice infected with prions. Journal of Virology, 83, 5918–5927.
Amano, S., Li, S., Gu, C., Gao, Y., Koizumi, S., Yamamoto, S., et al. (2009). Use of genetically engineered bone marrow-derived mesenchymal stem cells for glioma gene therapy. International Journal of Oncology, 35, 1265–1270.
Venkataramana, N. K., Kumar, S. K., Balaraju, S., Radhakrishnan, R. C., Bansal, A., Dixit, A., et al. (2010). Open-labeled study of unilateral autologous bone-marrow-derived mesenchymal stem cell transplantation in Parkinson’s disease. Translational Research, 155, 62–70.
Mazzini, L., Mareschi, K., Ferrero, I., Vassallo, E., Oliveri, G., Nasuelli, N., et al. (2008). Stem cell treatment in amyotrophic lateral sclerosis. Journal of the Neurological Sciences, 265, 78–83.
Mazzini, L., Ferrero, I., Luparello, V., Rustichelli, D., Gunetti, M., Mareschi, K., et al. (2010). Mesenchymal stem cell transplantation in amyotrophic lateral sclerosis: A PHASE I clinical trial. Experimental Neurology, 223(1), 229–237.
Lee, P. H., Kim, J. W., Bang, O. Y., Ahn, Y. H., Joo, I. S., & Huh, K. (2008). Autologous mesenchymal stem cell therapy delays the progression of neurological deficits in patients with multiple system atrophy. Clinical Pharmacology and Therapeutics, 83, 723–730.
Bang, O. Y., Lee, J. S., Lee, P. H., & Lee, G. (2005). Autologous mesenchymal stem cell transplantation in stroke patients. Annals of Neurology, 57, 874–882.
Enzmann, G. U., Benton, R. L., Talbott, J. F., Cao, Q., & Whittemore, S. R. (2006). Functional considerations of stem cell transplantation therapy for spinal cord repair. Journal of Neurotrauma, 23, 479–495.
Callera, F., & do Nascimento, R. X. (2006). Delivery of autologous bone marrow precursor cells into the spinal cord via lumbar puncture technique in patients with spinal cord injury: a preliminary safety study. Experimental Hematology, 34, 130–131.
Parr, A., Tator, C., & Keating, A. (2007). Bone marrow-derived mesenchymal stromal cells for the repair of central nervous system injury. Bone Marrow Transplantation, 40, 609–619.
Yoon, S., Shim, Y., Park, Y., Chung, J., Nam, J., Kim, M., et al. (2007). Complete spinal cord injury treatment using autologous bone marrow cell transplantation and bone marrow stimulation with granulocyte macrophage-colony stimulating factor: Phase I/II clinical trial. Stem Cells, 25, 2066–2073.
Xue, y., Luo, Z., & Tian, S. (2005). A study on the culturing of human bone marrow stromal cells in vitro and its primary induction. Chinese Journal of Spine and Spinal Cord, 15, 594–597.
Hofstetter, C. P., Holmstrom, N. A., Lilja, J. A., Schweinhardt, P., Hao, J., Spenger, C., et al. (2005). Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome. Nature Neuroscience, 8, 346–353.
Cao, Q. L., Zhang, Y. P., Howard, R. M., Walters, W. M., Tsoulfas, P., & Whittemore, S. R. (2001). Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage. Experimental Neurology, 167, 48–58.
Joannides, A. J., Webber, D. J., Raineteau, O., Kelly, C., Irvine, K. A., Watts, C., et al. (2007). Environmental signals regulate lineage choice and temporal maturation of neural stem cells from human embryonic stem cells. Brain, 130, 1263–1275.
Low, C. B., Liou, Y. C., & Tang, B. L. (2008). Neural differentiation and potential use of stem cells from the human umbilical cord for central nervous system transplantation therapy. Journal of Neuroscience Research, 86, 1670–1679.
Kang, X. Q., Zang, W. J., Bao, L. J., Li, D. L., Xu, X. L., & Yu, X. J. (2006). Differentiating characterization of human umbilical cord blood-derived mesenchymal stem cells in vitro. Cell Biology International, 30, 569–575.
Woodbury, D., Schwarz, E. J., Prockop, D. J., & Black, I. B. (2000). Adult rat and human bone marrow stromal cells differentiate into neurons. Journal of Neuroscience Research, 61, 364–370.
Kogler, G., Sensken, S., Airey, J. A., Trapp, T., Muschen, M., Feldhahn, N., et al. (2004). A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. Journal of Experimental Medicine, 200, 123–135.
Yong-zhou, S., Hui-xian, C., Zhe, L., & Xin-sheng, W. (2008). Effects of brain homogenate on the differentiation of rat bone mesenchymal stem cells into neuron-like cells following traumatic brain injury. Journal of Clinical Rehabilitative Tissue Engineering Research, 12, 461–464.
Wang, X. S., Zhao, Y., Li, H. F., & Zhang, X. L. (2009). Astragalus mongholicus-induced differentiation of rat bone marrow mesenchymal stem cells. Journal of Clinical Rehabilitative Tissue Engineering Research, 19, 3785–3789.
Lu, C. Q. L. R., & Zhang, Q. B. (2008). Gene expression in differentiation of rat bone marrow-derived mesenchymal stem cells into neurocyte-like cells induced by salvia mitiorrhiza. Journal of Clinical Rehabilitative Tissue Engineering Research, 47, 9363–9366.
Han, X. G., Li, J. B., & Ma, J. J. (2009). Induced differentiation of adult bone marrow mesenchymal stem cell to wards neuron-like cells: The best inducer and induction time. Journal of Clinical Rehabilitative Tissue Engineering Research, 32, 6332–6337.
Tureyen, K., Vemuganti, R., Bowen, K. K., Sailor, K. A., & Dempsey, R. J. (2005). EGF and FGF-2 infusion increases post-ischemic neural progenitor cell proliferation in the adult rat brain. Neurosurgery, 57, 1254–1263. (discussion 1254–1263).
Grundstrom, E., Lindholm, D., Johansson, A., Blennow, K., & Askmark, H. (2000). GDN but not BDNF is increased in cerebrospinal fluid in amyotrophic lateral sclerosis. Neuroreport, 11, 1781–1783.
Huang, C. C., Liu, C. C., Wang, S. T., Chang, Y. C., Yang, H. B., & Yeh, T. F. (1999). Basic fibroblast growth factor in experimental and clinical bacterial meningitis. Pediatric Research, 45, 120–127.
Sanchez-Ramos, J., Song, S., Cardozo-Pelaez, F., Hazzi, C., Stedeford, T., Willing, A., et al. (2000). Adult bone marrow stromal cells differentiate into neural cells in vitro. Experimental Neurology, 164, 247–256.
Acknowledgments
This work was supported in part by a grant of the National Natural Science Foundation of China (NSFC30972834 to Dr. Lu, China and the Natural Science Foundation of Xuzhou City (XM09B119 to Dr. Ye, China).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Ye, Y., Zeng, YM., Wan, MR. et al. Induction of Human Bone Marrow Mesenchymal Stem Cells Differentiation into Neural-Like Cells Using Cerebrospinal Fluid. Cell Biochem Biophys 59, 179–184 (2011). https://doi.org/10.1007/s12013-010-9130-z
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12013-010-9130-z