Influence of local environment on the differentiation of neural stem cells engrafted onto the injured spinal cord

Giovanna Petrucci, Liverana Lauretti, Nicola Montano, Luigi Maria Larocca, Ruggero De Maria Marchiano, Roberto Pallini, Quintino Giorgio D'Alessandris, Eduardo Marcos Fernandez Marquez, Giulio Maira, Lucia Ricci-Vitiani, Patrizia Casalbore, Maria Laura Falchetti, Dario Giuseppe Lombardi, Valeria Di Giorgio Gerevini, Carlo Cenciarelli, Cesare Peschle, Eugenio Parati

Risultato della ricerca: Contributo in rivistaArticolo in rivista

39 Citazioni (Scopus)

Abstract

Objectives: In vitro, neural stem cells (NSCs) proliferate as undifferentiated spheroids and differentiate into neurons, astrocytes and oligodendrocytes. These features make NSCs suitable for spinal cord (SC) reconstruction. However, in vivo experiments have demonstrated that in the injured SC transplanted NSCs either remain undifferentiated or differentiate into the astrocytic phenotype. The microenvironment of the injured SC is believed to play a crucial role in driving the differentiation of the engrafted NSCs. Here, we tested the hypothesis that inflammatory cytokines (ICs) may be involved in the restricted differentiation of NSCs after grafting onto the injured SC. Methods: As the first step, we used immunohistochemistry to analyse the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and interferon (IFN)-γ in the normal SC of mice and following traumatic injury. Then, we investigated whether a combination of TNF-α, IL-1β and IFN-γ may affect the phenotype of murine NSCs in vitro. Results: We found that TNF-α, IL- 1β and IFN-γ, which are absent in the normal SC, are all expressed in the injured SC and the expression of these cytokines follows a timely tuned fashion with IFN-γ being detectable as long as 4 weeks after injury. In culture, exposure of proliferating NSCs to a combination of TNF-α, IL-1β and IFN-γ was per se sufficient to induce the astrocytic differentiation of these cells even in the absence of serum. Conclusions: In the traumatically injured SC, differentiation of engrafted NSCs is restricted towards the astrocytic lineage because of the inflammatory environment. ICs are likely to play a major role in differentiation of NSCs in the in vivo conditions. © 2006 W. S. Maney & Son Ltd.
Lingua originaleEnglish
pagine (da-a)488-492
Numero di pagine5
RivistaNeurological Research
Volume28
DOI
Stato di pubblicazionePubblicato - 2006

Keywords

  • Animals
  • Astrocytes
  • Astrocytic differentiation
  • Cell Differentiation
  • Cytokines
  • Female
  • Immunohistochemistry
  • Inflammatory cytokines
  • Interferon-gamma
  • Interleukin-1
  • Medicine (all)
  • Mice
  • Neural stem cells
  • Neurology
  • Neurology (clinical)
  • Neurons
  • Spinal Cord Injuries
  • Spinal cord injury
  • Stem Cell Transplantation
  • Tumor Necrosis Factor-alpha

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