Neurochemical Research

, Volume 32, Issue 2, pp 353–362 | Cite as

Human Mesenchymal Stem Cells Signals Regulate Neural Stem Cell Fate

  • Lianhua Bai
  • Arnold Caplan
  • Donald Lennon
  • Robert H. Miller
Original Paper

Abstract

Neural stem cells (NSCs) differentiate into neurons, astrocytes and oligodendrocytes depending on their location within the central nervous system (CNS). The cellular and molecular cues mediating end-stage cell fate choices are not completely understood. The retention of multipotent NSCs in the adult CNS raises the possibility that selective recruitment of their progeny to specific lineages may facilitate repair in a spectrum of neuropathological conditions. Previous studies suggest that adult human bone marrow derived mesenchymal stem cells (hMSCs) improve functional outcome after a wide range of CNS insults, probably through their trophic influence. In the context of such trophic activity, here we demonstrate that hMSCs in culture provide humoral signals that selectively promote the genesis of neurons and oligodendrocytes from NSCs. Cell–cell contacts were less effective and the proportion of hMSCs that could be induced to express neural characteristics was very small. We propose that the selective promotion of neuronal and oligodendroglial fates in neural stem cell progeny is responsible for the ability of MSCs to enhance recovery after a wide range of CNS injuries.

Keywords

Neural stem cells MSCs Migration Differentiation Neurons Oligodendrocytes 

References

  1. 1.
    Reynolds BA, Rietze RL (2005) Neural stem cells and neurospheres—re-evaluating the relationship. Nat Methods 2:333–336PubMedCrossRefGoogle Scholar
  2. 2.
    Pluchino S et al (2005) Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism. Nature 436:266–271PubMedCrossRefGoogle Scholar
  3. 3.
    Bossolasco P et al (2005) Neuro-glial differentiation of human bone marrow stem cells in vitro. Exp Neurol 193:312–325PubMedCrossRefGoogle Scholar
  4. 4.
    Wislet-Gendebien S et al (2005) Plasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype. Stem Cells 23:392–402PubMedCrossRefGoogle Scholar
  5. 5.
    Li Y et al (2005) Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells. Glia 49:407–417PubMedCrossRefGoogle Scholar
  6. 6.
    Deng YB et al (2006) Implantation of BM mesenchymal stem cells into injured spinal cord elicits de novo neurogenesis and functional recovery: evidence from a study in rhesus monkeys. Cytotherapy 8:210–214PubMedCrossRefGoogle Scholar
  7. 7.
    Pittenger MF et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147PubMedCrossRefGoogle Scholar
  8. 8.
    Ferrari G et al (1998) Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279:1528–1530PubMedCrossRefGoogle Scholar
  9. 9.
    Prockop DJ (1997) Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 276:71–74PubMedCrossRefGoogle Scholar
  10. 10.
    Deans RJ, Moseley AB (2000) Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol 28:875–884PubMedCrossRefGoogle Scholar
  11. 11.
    Sanchez-Ramos J et al (2000) Adult bone marrow stromal cells differentiate into neural cells in vitro. Exp Neurol 164:247–256PubMedCrossRefGoogle Scholar
  12. 12.
    Lu P, Blesch A, Tuszynski MH (2004) Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact? J Neurosci Res 77:174–191PubMedCrossRefGoogle Scholar
  13. 13.
    Keilhoff G et al (2006) Transdifferentiation of mesenchymal stem cells into Schwann cell-like myelinating cells. Eur J Cell Biol 85:11–24PubMedCrossRefGoogle Scholar
  14. 14.
    Kang SK et al (2003) Interactions between human adipose stromal cells and mouse neural stem cells in vitro. Brain Res Dev Brain Res 145:141–149PubMedCrossRefGoogle Scholar
  15. 15.
    Bonab MM et al (2006) Aging of mesenchymal stem cell in vitro. BMC Cell Biol 7:14PubMedCrossRefGoogle Scholar
  16. 16.
    Itoh T et al (2005) Isolation of neural stem cells from damaged rat cerebral cortex after traumatic brain injury. Neuroreport 16:1687–1691PubMedCrossRefGoogle Scholar
  17. 17.
    Mingorance A et al (2005) Overexpression of myelin-associated glycoprotein after axotomy of the perforant pathway. Mol Cell Neurosci 29:471–483PubMedCrossRefGoogle Scholar
  18. 18.
    Bryceson YT et al (2005) Expression of a killer cell receptor-like gene in plastic regions of the central nervous system. J Neuroimmunol 161:177–182PubMedCrossRefGoogle Scholar
  19. 19.
    Soukup T et al (2006) Mesenchymal stem cells isolated from the human bone marrow: cultivation, phenotypic analysis and changes in proliferation kinetics. Acta Medica (Hradec Kralove) 49:27–33Google Scholar
  20. 20.
    Barry F et al (2001) The SH-3 and SH-4 antibodies recognize distinct epitopes on CD73 from human mesenchymal stem cells. Biochem Biophys Res Commun 289:519–524PubMedCrossRefGoogle Scholar
  21. 21.
    Mothe AJ et al (2005) Analysis of green fluorescent protein expression in transgenic rats for tracking transplanted neural stem/progenitor cells. J Histochem Cytochem 53:1215–1226PubMedCrossRefGoogle Scholar
  22. 22.
    Deng J et al (2006) Mesenchymal stem cells spontaneously express neural proteins in culture and are neurogenic after transplantation. Stem Cells 24:1054–1064PubMedCrossRefGoogle Scholar
  23. 23.
    Bertani N et al (2006) Neurogenic potential of human mesenchymal stem cells revisited: analysis by immunostaining, timelapse video and microarray. J Cell Sci 118:3925–3936CrossRefGoogle Scholar
  24. 24.
    Ribotta MG, Menet V, Privat A (2004) Glial scar and axonal regeneration in the CNS: lessons from GFAP and vimentin transgenic mice. Acta Neurochir Suppl 89:87–92PubMedGoogle Scholar
  25. 25.
    Andrae J et al (2004) Forced expression of platelet-derived growth factor B in the mouse cerebellar primordium changes cell migration during midline fusion and causes cerebellar ectopia. Mol Cell Neurosci 26:308–321PubMedCrossRefGoogle Scholar
  26. 26.
    Vasyutina E et al (2005) CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells. Genes Dev 19:2187–2198PubMedCrossRefGoogle Scholar
  27. 27.
    Ge Y et al (2006) Fibroblast activation protein (FAP) is upregulated in myelomatous bone and supports myeloma cell survival. Br J Haematol 133:83–92PubMedCrossRefGoogle Scholar
  28. 28.
    Kawasaki H et al (2000) Induction of midbrain dopaminergic neurons from ES cells by stromal cell-derived inducing activity. Neuron 28:31–40PubMedCrossRefGoogle Scholar
  29. 29.
    Kawasaki H et al (2002) Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity. Proc Natl Acad Sci USA 99:1580–1585PubMedCrossRefGoogle Scholar
  30. 30.
    Conget PA, Minguell JJ (1999) Phenotypical and functional properties of human bone marrow mesenchymal progenitor cells. J Cell Physiol 181:67–73PubMedCrossRefGoogle Scholar
  31. 31.
    Hanabusa K et al (2005) Adrenomedullin enhances therapeutic potency of mesenchymal stem cells after experimental stroke in rats. Stroke 36:853–858PubMedCrossRefGoogle Scholar
  32. 32.
    Ito J et al (2005) A new method for drug application to the inner ear. ORL J Otorhinolaryngol Relat Spec 67:272–275PubMedGoogle Scholar
  33. 33.
    Tsai HH et al (2002) The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell 110:373–383PubMedCrossRefGoogle Scholar
  34. 34.
    Studeny M et al (2004) Mesenchymal stem cells: potential precursors for tumor stroma and targeted-delivery vehicles for anticancer agents. J Natl Cancer Inst 96:1593–1603PubMedCrossRefGoogle Scholar
  35. 35.
    Wang L et al (2002) Ischemic cerebral tissue and MCP-1 enhance rat bone marrow stromal cell migration in interface culture. Exp Hematol 30:831–836PubMedCrossRefGoogle Scholar
  36. 36.
    Bhakta S, Hong P, Koc O (2006) The surface adhesion molecule CXCR4 stimulates mesenchymal stem cell migration to stromal cell-derived factor-1 in vitro but does not decrease apoptosis under serum deprivation. Cardiovasc Revasc Med 7:19–24PubMedCrossRefGoogle Scholar
  37. 37.
    Lu ZL, Lesmes LA, Sperling G (1999) The mechanism of isoluminant chromatic motion perception. Proc Natl Acad Sci USA 96:8289–8294PubMedCrossRefGoogle Scholar
  38. 38.
    Abu-Ghazaleh R et al (2001) Src mediates stimulation by vascular endothelial growth factor of the phosphorylation of focal adhesion kinase at tyrosine 861, and migration and anti-apoptosis in endothelial cells. Biochem J 360:255–264PubMedCrossRefGoogle Scholar
  39. 39.
    Ruoslahti E (1997) Integrins as signaling molecules and targets for tumor therapy. Kidney Int 51:1413–1417PubMedGoogle Scholar
  40. 40.
    Gregory CA, Ylostalo J, Prockop DJ (2005) Adult bone marrow stem/progenitor cells (MSCs) are preconditioned by microenvironmental “niches” in culture: a two-stage hypothesis for regulation of MSC fate. Sci STKE 2005, pe37Google Scholar
  41. 41.
    Haggiag S et al (2001) Stimulation of myelin gene expression in vitro and of sciatic nerve remyelination by interleukin-6 receptor-interleukin-6 chimera. J Neurosci Res 64:564–574PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Lianhua Bai
    • 1
  • Arnold Caplan
    • 2
  • Donald Lennon
    • 2
  • Robert H. Miller
    • 1
  1. 1.Centers for Stem Cells and Regenerative Medicine, Translational Neuroscience, Department of Neurosciences, Case School of MedicineCase Western Reserve UniversityClevelandUSA
  2. 2.Skeletal Research CenterCase Western Reserve UniversityClevelandUSA

Personalised recommendations