Downregulation of thymosin beta4 in neural progenitor grafts promotes spinal cord regeneration

Ruggero De Maria Marchiano, Roberto Pallini, Corrado Lucantoni, Cristiana Mollinari, Lucia Ricci-Vitiani, Massimo Pieri, Anna Maria Rinaldi, Mauro Racaniello, Cristina Zona, Daniela Merlo, Enrico Garaci

Risultato della ricerca: Contributo in rivistaArticolo in rivista

23 Citazioni (Scopus)

Abstract

Thymosin β4 (Tβ4) is an actin-binding peptide whose expression in developing brain correlates with migration and neurite extension of neurons. Here, we studied the effects of the downregulation of Tβ4 expression on growth and differentiation of murine neural progenitor cells (NPCs), using an antisense lentiviral vector. In differentiation-promoting medium, we found twice the number of neurons derived from the Tβ4-antisense-transduced NPCs, which showed enhanced neurite outgrowth accompanied by increased expression of the adhesion complex N-cadherin-β-catenin and increased ERK activation. Importantly, when the Tβ4-antisense-transduced NPCs were transplanted in vivo into a mouse model of spinal cord injury, they promoted a significantly greater functional recovery. Locomotory recovery correlated with increased expression of the regeneration-promoting cell adhesion molecule L1 by the grafted Tβ4-antisense-transduced NPCs. This resulted in an increased number of regenerating axons and in sprouting of serotonergic fibers surrounding and contacting the Tβ4-antisense-transduced NPCs grafted into the lesion site. In conclusion, our data identify a new role for Tβ4 in neuronal differentiation of NPCs by regulating fate determination and process outgrowth. Moreover, NPCs with reduced Tβ4 levels generate an L1-enriched environment in the lesioned spinal cord that favors growth and sprouting of spared host axons and enhances the endogenous tissue-repair processes.
Lingua originaleEnglish
pagine (da-a)4195-4207
Numero di pagine13
RivistaJournal of Cell Science
Volume122
DOI
Stato di pubblicazionePubblicato - 2009

Keywords

  • Adhesion molecules
  • Animals
  • Axons
  • Cadherins
  • Cell Biology
  • Cell Communication
  • DNA, Antisense
  • Disease Models, Animal
  • Down-Regulation
  • Mice
  • Nerve Regeneration
  • Neural Cell Adhesion Molecule L1
  • Neural progenitor cell graft
  • Neurite outgrowth
  • Neurogenesis
  • Neuronal differentiation
  • Neurons
  • Spinal Cord Injuries
  • Spinal cord injury
  • Stem Cell Transplantation
  • Stem Cells
  • Telencephalon
  • Thymosin
  • Thymosin β4
  • beta Catenin

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