Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation

Angelo L. Vescovi, Eugenio A. Parati, Angela Gritti, Paule Poulin, Marina Ferrario, Enzo Wanke, Paola Frölichsthal-Schoeller, Lidia Cova, Mayi Arcellana-Panlilio, Augusto Colombo, Rossella Galli

Research output: Contribution to journalArticle

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Abstract

Stem cells that can give rise to neurons, astroglia, and oligodendroglia have been found in the developing and adult central nervous system (CNS) of rodents. Yet, their existence within the human brain has not been documented, and the isolation and characterization of multipotent embryonic human neural stem cells have proven difficult to accomplish. We show that the developing human CNS embodies multipotent precursors that differ from their murine counterpart in that they require simultaneous, synergistic stimulation by both epidermal and fibroblast growth factor-2 to exhibit critical stem cell characteristics. Clonal analysis demonstrates that human C NS stem cells are multipotent and differentiate spontaneously into neurons, astrocytes, and oligodendrocytes when growth factors are removed. Subcloning and population analysis show their extensive self-renewal capacity and functional stability, their ability to maintain a steady growth profile, their multipotency, and a constant potential for neuronal differentiation for more than 2 years. The neurons generated by human stem cells over this period of time are electrophysiologically active. These cells are also cryopreservable. Finally, we demonstrate that the neuronal and glial progeny of long-term cultured human CNS stem cells can effectively survive transplantation into the lesioned striatum of adult rats. Tumor formation is not observed, even in immunodeficient hosts. Hence, as a consequence of their inherent biology, human CNS stem cells can establish stable, transplantable cell lines by epigenetic stimulation. These lines represent a renewable source of neurons and glia and may significantly facilitate research on human neurogenesis and the development of clinical neural transplantation.

Original languageEnglish
Pages (from-to)71-83
Number of pages13
JournalExperimental Neurology
Volume156
Issue number1
DOIs
Publication statusPublished - Mar 1999

Fingerprint

Neural Stem Cells
Epigenomics
Organism Cloning
Central Nervous System
Cell Line
Stem Cells
Neurons
Oligodendroglia
Neuroglia
Astrocytes
Transplantation
Multipotent Stem Cells
Aptitude
Neurogenesis
Human Development
Human Embryonic Stem Cells
Epidermal Growth Factor
Rodentia
Intercellular Signaling Peptides and Proteins
Fibroblasts

Keywords

  • EGF
  • FGF2
  • Human CNS stem cells
  • Human neural precursors
  • Transplantation

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Isolation and cloning of multipotential stem cells from the embryonic human CNS and establishment of transplantable human neural stem cell lines by epigenetic stimulation. / Vescovi, Angelo L.; Parati, Eugenio A.; Gritti, Angela; Poulin, Paule; Ferrario, Marina; Wanke, Enzo; Frölichsthal-Schoeller, Paola; Cova, Lidia; Arcellana-Panlilio, Mayi; Colombo, Augusto; Galli, Rossella.

In: Experimental Neurology, Vol. 156, No. 1, 03.1999, p. 71-83.

Research output: Contribution to journalArticle

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