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.
| Original language | English |
|---|---|
| Pages (from-to) | 488-492 |
| Number of pages | 5 |
| Journal | Neurological Research |
| Volume | 28 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Jul 2006 |
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Keywords
- Astrocytic differentiation
- Inflammatory cytokines
- Neural stem cells
- Spinal cord injury
ASJC Scopus subject areas
- Clinical Neurology
- Neuroscience(all)
Cite this
Influence of local environment on the differentiation of neural stem cells engrafted onto the injured spinal cord. / Ricci-Vitiani, Lucia; Casalbore, Patrizia; Petrucci, Giovanna; Lauretti, Liverana; Montano, Nicola; Larocca, Luigi Maria; Falchetti, Maria Laura; Lombardi, Dario Giuseppe; Gerevini, Valeria Di Giorgio; Cenciarelli, Carlo; D'Alessandris, Quintino Giorgio; Fernandez, Eduardo; De Maria, Ruggero; Maira, Giulio; Peschle, Cesare; Parati, Eugenio; Pallini, Roberto.
In: Neurological Research, Vol. 28, No. 5, 07.2006, p. 488-492.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Influence of local environment on the differentiation of neural stem cells engrafted onto the injured spinal cord
AU - Ricci-Vitiani, Lucia
AU - Casalbore, Patrizia
AU - Petrucci, Giovanna
AU - Lauretti, Liverana
AU - Montano, Nicola
AU - Larocca, Luigi Maria
AU - Falchetti, Maria Laura
AU - Lombardi, Dario Giuseppe
AU - Gerevini, Valeria Di Giorgio
AU - Cenciarelli, Carlo
AU - D'Alessandris, Quintino Giorgio
AU - Fernandez, Eduardo
AU - De Maria, Ruggero
AU - Maira, Giulio
AU - Peschle, Cesare
AU - Parati, Eugenio
AU - Pallini, Roberto
PY - 2006/7
Y1 - 2006/7
N2 - 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.
AB - 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.
KW - Astrocytic differentiation
KW - Inflammatory cytokines
KW - Neural stem cells
KW - Spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=33746575019&partnerID=8YFLogxK
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U2 - 10.1179/016164106X115134
DO - 10.1179/016164106X115134
M3 - Article
VL - 28
SP - 488
EP - 492
JO - Neurological Research
JF - Neurological Research
SN - 0161-6412
IS - 5
ER -