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New Hot Paper Comments

By Angelo L. Vescovi

ESI Special Topics, September 2002
Citing URL - http://www.esi-topics.com/nhp/comments/september-02-AngeloVescovi.html

Angelo L. Vescovi answers a few questions about this month's new hot paper in the field of Neuroscience and Behavior


From •>>September 2002

Field: Neuroscience & Behavior
Article Title: "Skeletal myogenic potential of human and mouse neural stem cells"
Authors: Galli, R;Borello, U;Gritti, A;Minasi, AG;Bjornson, C;Coletta, M;Mora, M;De Angelis, MGC;Fiocco, R;Cossu, G;Vescovi, AL
Journal: NAT NEUROSCI
Volume: 3
Page: 986-991
Year: OCT 2000
* Natl Neurol Inst C Besta, Via Celoria 11, I-20133 Milan, Italy.
* Natl Neurol Inst C Besta, I-20133 Milan, Italy.
* HS Raffaele, Stem Cell Res Inst, I-20133 Milan, Italy.
* Univ Rome La Sapienza, Dept Histol & Med Embryol, Fdn Pasteur Cenci Bolognetti, I-00161 Rome, Italy.
* Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
* Univ Pavia, Dept Expt Med, I-27100 Pavia, Italy.

ST:  Why do you think your paper is highly cited?

The field of stem cell research is one of the most exciting areas of research nowadays, particularly as concerns its application in cell therapeutics and the consequential clinical and health-related implications.

Recently, stem cells have been identified also in the adult central nervous system where they constitute a continuous source of new neurons to be exploited for cell-based therapy of neurodegenerative diseases. In 1999 our group had been the first to report on theTop to bottom: Angelo L. Vescovi, Director and Rosella Galli, Senior Staff Scientist unexpected plasticity of CNS stem cells which were shown to be able to convert into blood cells. In this context, this article was the first to confirm the highly debated finding that neural cells could give rise to non-neural tissues of the mesodermal lineage in the context of adult tissues by showing that they can differentiate into skeletal muscle. Notably, this phenomenon was demonstrated not only by transplanting adult neural stem cells into lesioned animals but also by means of an in vitro system based on cocultures of neural stem cells with muscle cells.

ST:  Does it describe a new discovery or new methodology that's useful to others?

As mentioned above, these results not only confirm the pioneering demonstration of extra-neural potential of adult neural stem cells but also provide researchers with a very handy in vitro tool by which mechanisms underlying the phenomenon of transdifferentiation can be analyzed in a quantitative fashion. Furthermore, in this work we showed that it is only the undifferentiated brain precursors that undergo transdifferentiation whereas their mature progeny does not. Finally, the phenomenon does not depend on exposing cells to growth factors in vitro.

ST:  What were some of the circumstances that led you to do this research?

The discovery made in 1999 that adult neural stem cells can convert into blood cells challenged a long-standing dogma in developmental biology—that cells derived from a given germ layer (neural cells are from the ectoderm) may give rise to non-ectodermal derivatives (blood is mesodermal in origin). This work was designed to show that neuro-mesodermal conversion does not occur serendipitously but rather, that it is an intrinsic feature of adult neural stem cells.

ST:  Could you summarize the significance of your paper in layman's terms?

Stem cells are the fundamental building blocks by which tissues and organs are built during development. In some tissues such as blood, skin and gut, these building blocks remain active throughout adulthood and contribute to the maintenance and regeneration of tissues by producing the mature cell types that provide the tissue itself with its appropriate functional characteristics. For example, stem cells of the blood make red blood cells, lymphocytes, whereas stem cells of the skin make mature keratinocytes. It has long been held that adult stem cells can generate exclusively mature cells that are typical of the tissue in which they reside.

Stem cells have been identified also in the mature brain, from which they can be isolated and grown in vitro for long periods. Upon modifications of the growth conditions, these stem cells can produce neurons and glia, the two main lineages of the CNS. What we reported in this article is the ability of adult stem cells, isolated from the brain, to produce not only brain cell types but also cells of a different origin and location such as muscle cells.

This conversion has been achieved either by injecting neural stem cells into the damaged muscle of mice or by mixing stem cells from the brain with stem cells from the muscle. In both cases, muscle cells instructed part of the brain stem cells to change their fate and transform into muscle cells. The rest of the nervous cells differentiated along their expected developmental "road" i.e. generated neurons and glia.End

Angelo L. Vescovi, Director
Rosella Galli, Senior Staff Scientist
Stem Cell Research institute
DIBIT HSR
Via Olgettina 58 Milan I-20132, Italy

ESI Special Topics, September 2002
Citing URL - http://www.esi-topics.com/nhp/comments/september-02-AngeloVescovi.html

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