Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model

Daniela Ferrari, Cristina Zalfa, Laura Rota Nodari, Maurizio Gelati, Luigi Carlessi, Domenico Delia, Angelo Luigi Vescovi, Lidia De Filippis

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Cell therapy is reaching the stage of phase I clinical trials for post-traumatic, post-ischemic, or neurodegenerative disorders, and the selection of the appropriate cell source is essential. In order to assess the capacity of different human neural stem cell lines (hNSC) to contribute to neural tissue regeneration and to reduce the local inflammation after an acute injury, we transplanted GMP grade non-immortalized hNSCs and v-myc (v-IhNSC), c-myc T58A (T-IhNSC) immortalized cells into the corpus callosum of adult rats after 5 days from focal demyelination induced by lysophosphatidylcholine. At 15 days from transplantation, hNSC and T-IhNSC migrated to the lesioned area where they promoted endogenous remyelination and differentiated into mature oligodendrocytes, while the all three cell lines were able to integrate in the SVZ. Moreover, where demyelination was accompanied by an inflammatory reaction, a significant reduction of microglial cells activation was observed. This effect correlated with a differential migratory pattern of transplanted hNSC and IhNSC, significantly enhanced in the former, thus suggesting a specific NSC-mediated immunomodulatory effect on the local inflammation. We provide evidence that, in the subacute phase of a demyelination injury, different human immortalized and non-immortalized NSC lines, all sharing homing to the stem niche, display a differential pathotropism, both through cell-autonomous and non-cell autonomous effects. Overall, these findings promote IhNSC as an inexhaustible cell source for large-scale preclinical studies and non-immortalized GMP grade hNSC lines as an efficacious, safe, and reliable therapeutic tool for future clinical applications.

Original languageEnglish
Pages (from-to)1193-1210
Number of pages18
JournalCellular and Molecular Life Sciences
Volume69
Issue number7
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Neural Stem Cells
Demyelinating Diseases
Cell Line
Inflammation
Lysophosphatidylcholines
Clinical Trials, Phase I
Corpus Callosum
Oligodendroglia
Wounds and Injuries
Cell- and Tissue-Based Therapy
Neurodegenerative Diseases
Regeneration
Transplantation

Keywords

  • Fetal Human Neural Stem Cells
  • Immunomodulation
  • Lysophosphatidylcoline
  • Re-myelination
  • Transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine
  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model. / Ferrari, Daniela; Zalfa, Cristina; Nodari, Laura Rota; Gelati, Maurizio; Carlessi, Luigi; Delia, Domenico; Vescovi, Angelo Luigi; De Filippis, Lidia.

In: Cellular and Molecular Life Sciences, Vol. 69, No. 7, 04.2012, p. 1193-1210.

Research output: Contribution to journalArticle

Ferrari, Daniela ; Zalfa, Cristina ; Nodari, Laura Rota ; Gelati, Maurizio ; Carlessi, Luigi ; Delia, Domenico ; Vescovi, Angelo Luigi ; De Filippis, Lidia. / Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model. In: Cellular and Molecular Life Sciences. 2012 ; Vol. 69, No. 7. pp. 1193-1210.
@article{32d27285f3274f558d8969c3c9b57773,
title = "Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model",
abstract = "Cell therapy is reaching the stage of phase I clinical trials for post-traumatic, post-ischemic, or neurodegenerative disorders, and the selection of the appropriate cell source is essential. In order to assess the capacity of different human neural stem cell lines (hNSC) to contribute to neural tissue regeneration and to reduce the local inflammation after an acute injury, we transplanted GMP grade non-immortalized hNSCs and v-myc (v-IhNSC), c-myc T58A (T-IhNSC) immortalized cells into the corpus callosum of adult rats after 5 days from focal demyelination induced by lysophosphatidylcholine. At 15 days from transplantation, hNSC and T-IhNSC migrated to the lesioned area where they promoted endogenous remyelination and differentiated into mature oligodendrocytes, while the all three cell lines were able to integrate in the SVZ. Moreover, where demyelination was accompanied by an inflammatory reaction, a significant reduction of microglial cells activation was observed. This effect correlated with a differential migratory pattern of transplanted hNSC and IhNSC, significantly enhanced in the former, thus suggesting a specific NSC-mediated immunomodulatory effect on the local inflammation. We provide evidence that, in the subacute phase of a demyelination injury, different human immortalized and non-immortalized NSC lines, all sharing homing to the stem niche, display a differential pathotropism, both through cell-autonomous and non-cell autonomous effects. Overall, these findings promote IhNSC as an inexhaustible cell source for large-scale preclinical studies and non-immortalized GMP grade hNSC lines as an efficacious, safe, and reliable therapeutic tool for future clinical applications.",
keywords = "Fetal Human Neural Stem Cells, Immunomodulation, Lysophosphatidylcoline, Re-myelination, Transplantation",
author = "Daniela Ferrari and Cristina Zalfa and Nodari, {Laura Rota} and Maurizio Gelati and Luigi Carlessi and Domenico Delia and Vescovi, {Angelo Luigi} and {De Filippis}, Lidia",
year = "2012",
month = "4",
doi = "10.1007/s00018-011-0873-5",
language = "English",
volume = "69",
pages = "1193--1210",
journal = "Cellular and Molecular Life Sciences",
issn = "1420-682X",
publisher = "Birkhauser Verlag Basel",
number = "7",

}

TY - JOUR

T1 - Differential pathotropism of non-immortalized and immortalized human neural stem cell lines in a focal demyelination model

AU - Ferrari, Daniela

AU - Zalfa, Cristina

AU - Nodari, Laura Rota

AU - Gelati, Maurizio

AU - Carlessi, Luigi

AU - Delia, Domenico

AU - Vescovi, Angelo Luigi

AU - De Filippis, Lidia

PY - 2012/4

Y1 - 2012/4

N2 - Cell therapy is reaching the stage of phase I clinical trials for post-traumatic, post-ischemic, or neurodegenerative disorders, and the selection of the appropriate cell source is essential. In order to assess the capacity of different human neural stem cell lines (hNSC) to contribute to neural tissue regeneration and to reduce the local inflammation after an acute injury, we transplanted GMP grade non-immortalized hNSCs and v-myc (v-IhNSC), c-myc T58A (T-IhNSC) immortalized cells into the corpus callosum of adult rats after 5 days from focal demyelination induced by lysophosphatidylcholine. At 15 days from transplantation, hNSC and T-IhNSC migrated to the lesioned area where they promoted endogenous remyelination and differentiated into mature oligodendrocytes, while the all three cell lines were able to integrate in the SVZ. Moreover, where demyelination was accompanied by an inflammatory reaction, a significant reduction of microglial cells activation was observed. This effect correlated with a differential migratory pattern of transplanted hNSC and IhNSC, significantly enhanced in the former, thus suggesting a specific NSC-mediated immunomodulatory effect on the local inflammation. We provide evidence that, in the subacute phase of a demyelination injury, different human immortalized and non-immortalized NSC lines, all sharing homing to the stem niche, display a differential pathotropism, both through cell-autonomous and non-cell autonomous effects. Overall, these findings promote IhNSC as an inexhaustible cell source for large-scale preclinical studies and non-immortalized GMP grade hNSC lines as an efficacious, safe, and reliable therapeutic tool for future clinical applications.

AB - Cell therapy is reaching the stage of phase I clinical trials for post-traumatic, post-ischemic, or neurodegenerative disorders, and the selection of the appropriate cell source is essential. In order to assess the capacity of different human neural stem cell lines (hNSC) to contribute to neural tissue regeneration and to reduce the local inflammation after an acute injury, we transplanted GMP grade non-immortalized hNSCs and v-myc (v-IhNSC), c-myc T58A (T-IhNSC) immortalized cells into the corpus callosum of adult rats after 5 days from focal demyelination induced by lysophosphatidylcholine. At 15 days from transplantation, hNSC and T-IhNSC migrated to the lesioned area where they promoted endogenous remyelination and differentiated into mature oligodendrocytes, while the all three cell lines were able to integrate in the SVZ. Moreover, where demyelination was accompanied by an inflammatory reaction, a significant reduction of microglial cells activation was observed. This effect correlated with a differential migratory pattern of transplanted hNSC and IhNSC, significantly enhanced in the former, thus suggesting a specific NSC-mediated immunomodulatory effect on the local inflammation. We provide evidence that, in the subacute phase of a demyelination injury, different human immortalized and non-immortalized NSC lines, all sharing homing to the stem niche, display a differential pathotropism, both through cell-autonomous and non-cell autonomous effects. Overall, these findings promote IhNSC as an inexhaustible cell source for large-scale preclinical studies and non-immortalized GMP grade hNSC lines as an efficacious, safe, and reliable therapeutic tool for future clinical applications.

KW - Fetal Human Neural Stem Cells

KW - Immunomodulation

KW - Lysophosphatidylcoline

KW - Re-myelination

KW - Transplantation

UR - http://www.scopus.com/inward/record.url?scp=84859164123&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859164123&partnerID=8YFLogxK

U2 - 10.1007/s00018-011-0873-5

DO - 10.1007/s00018-011-0873-5

M3 - Article

VL - 69

SP - 1193

EP - 1210

JO - Cellular and Molecular Life Sciences

JF - Cellular and Molecular Life Sciences

SN - 1420-682X

IS - 7

ER -