PLoS ONE: Human Neural Stem Cells Differentiate and Promote Locomotor Recovery in an Early Chronic Spinal coRd Injury NOD-scid Mouse Model

Human Neural Stem Cells Differentiate and Promote Locomotor Recovery in an Early Chronic Spinal coRd Injury NOD-scid Mouse Model

Traumatic spinal cord injury (SCI) results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns) were prospectively isolated based on fluorescence-activated cell sorting for a CD133+ and CD24−/lo population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.

hCNS-SCns were transplanted into immunodeficient NOD-scid mice 30 days post spinal cord contusion injury. hCNS-SCns transplanted mice demonstrated significantly improved locomotor recovery compared to vehicle controls using open field locomotor testing and CatWalk gait analysis. Transplanted hCNS-SCns exhibited long-term engraftment, migration, limited proliferation, and differentiation predominantly to oligodendrocytes and neurons. Astrocytic differentiation was rare and mice did not exhibit mechanical allodynia. Furthermore, differentiated hCNS-SCns integrated with the host as demonstrated by co-localization of human cytoplasm with discrete staining for the paranodal marker contactin-associated protein.

The results suggest that hCNS-SCns are capable of surviving, differentiating, and promoting improved locomotor recovery when transplanted into an early chronic injury microenvironment. These data suggest that hCNS-SCns transplantation has efficacy in an early chronic SCI setting and thus expands the “window of opportunity” for intervention.


Desirée L. Salazar1,2,3¤, Nobuko Uchida4, Frank P. T. Hamers5, Brian J. Cummings2,3,6#, Aileen J. Anderson1,2,3,6#*

1 Department of Anatomy and Neurobiology, University of California Irvine, Irvine, California, United States of America, 2 Sue and Bill Gross Stem Cell Research Center, University of California Irvine, Irvine, California, United States of America, 3 Reeve-Irvine Research Center, University of California Irvine, Irvine, California, United States of America, 4 StemCells, Inc., Palo Alto, California, United States of America, 5 Rehabilitation Hospital Tolbrug, 's Hertogenbosch, The Netherlands, 6 Department of Physical Medicine and Rehabilitation, University of California Irvine, Irvine, California United States of America

Abstract
Background
Traumatic spinal cord injury (SCI) results in partial or complete paralysis and is characterized by a loss of neurons and oligodendrocytes, axonal injury, and demyelination/dysmyelination of spared axons. Approximately 1,250,000 individuals have chronic SCI in the U.S.; therefore treatment in the chronic stages is highly clinically relevant. Human neural stem cells (hCNS-SCns) were prospectively isolated based on fluorescence-activated cell sorting for a CD133+ and CD24−/lo population from fetal brain, grown as neurospheres, and lineage restricted to generate neurons, oligodendrocytes and astrocytes. hCNS-SCns have recently been transplanted sub-acutely following spinal cord injury and found to promote improved locomotor recovery. We tested the ability of hCNS-SCns transplanted 30 days post SCI to survive, differentiate, migrate, and promote improved locomotor recovery.

full-text:
PLoS ONE: Human Neural Stem Cells Differentiate and Promote Locomotor Recovery in an Early Chronic Spinal coRd Injury NOD-scid Mouse Model




NEUROLOGÍA
Actualidad Ultimas noticias - JANOes y agencias -
Células madre consiguen que ratas con lesiones medulares mejoren su movimiento
JANO.es y agencias · 20 Agosto 2010 11:11

Científicos estadounidenses utilizaron células madre desarrolladas por la compañía StemCells, con las que se prevé iniciar ensayos clínicos el próximo año


Investigadores de la Universidad de California en Irvine (Estados Unidos) han conseguido que ratones con la médula espinal lesionada mejoren su movimiento tras emplear células madre humanas, incluso un mes después de producirse la lesión.

Los investigadores utilizaron células madre nerviosas que provenían de StemCells Inc, compañía que ya ha anunciado que pretende comenzar los ensayos en 2011n tras observar que estas se asentaron sin problema en la médula, consiguiendo expandirse y ayudando a los ratones a moverse mejor.

El trabajo se realizó con un tipo de células obtenidos de cerebros parcialmente desarrollados de fetos abortados y evaluadas en su calidad para ser destinadas a formar un tipo particular de célula nerviosa.

En el ensayo se evaluaron a 37 ratones a los que se les dañó la médula espinal mediante cirugía y luego se les transfundió el producto de StemCells, células comunes de la piel humana o un placebo. Cuando se evaluó la coordinación, el 64% de los ratones tratados con las células madre caminó mejor, comparado con el 44% de aquellos que recibieron células normales y con el 20% del grupo placebo.

El estudio, coordinado por la Dra. Aileen Anderson y publicado en PLoS ONE, abre una puerta a la esperanza a los pacientes con lesiones de la médula espinal, ya que se cree que el tratamiento podría ser posible incluso semanas después de producirse la lesión, según declaran los autores.

Hasta el momento la mayor parte de los estudios realizados ha demostrado que es muy difícil curar las lesiones medulares y que, en caso de intentarlo, para obtener algún resultado, debe realizarse a los pocos días de producida la lesión.

Para el vicepresidente de StemCells, Stephen Huhn, “estos resultados alentadores demuestran una ventana mayor de oportunidad para la intervención con células madre en las lesiones de la médula espinal” y “es una evidencia adicional de que el uso de células madre neuronales humanas sería un enfoque terapéutico viable para ellos”.

PLoS ONE 5(8): e12272. doi:10.1371/journal.pone.0012272
PLoS ONE: Human Neural Stem Cells Differentiate and Promote Locomotor Recovery in an Early Chronic Spinal coRd Injury NOD-scid Mouse Model

PLoS ONE
PLoS ONE : accelerating the publication of peer-reviewed science

StemCells, Inc.
http://www.stemcellsinc.com/

University of California Irvine
http://www.uci.edu/

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