Pablo Avalos | Universidad Nacional Agraria La Molina (original) (raw)
Papers by Pablo Avalos
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 19, 2014
Recently, there has been remarkable progress in understanding inherited forms of ALS in which wel... more Recently, there has been remarkable progress in understanding inherited forms of ALS in which well defined mutations are known to cause the disease. Rodent models in which the superoxide dismutase-1 (SOD1) mutation is overexpressed recapitulate hallmark signs of ALS in patients. Early anatomical changes in mouse models of fALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction of toxic mutant SOD1 in the spinal cord and muscle of these models has beneficial effects. Therefore, much of ALS research has focused on spinal motor neuron and NMJ aspects of the disease. Here we show that, in the SOD1 G93A rat model of ALS, spinal motor neuron loss occurs presymptomatically and before degeneration of ventral root axons and denervation of NMJs. Although overt cell death of corticospinal motor neurons does not occur until disease endpoint, we wanted to establish whether the upper motor neuron might still play a critical role in disease progression. Surprisingly, the knockdown of mutant SOD1 in only the motor cortex of presymptomatic SOD1 G93A rats through targeted delivery of AAV9 -SOD1-shRNA resulted in a significant delay of disease onset, expansion of lifespan, enhanced survival of spinal motor neurons, and maintenance of NMJs. This datum suggests an early dysfunction and thus an important role of the upper motor neuron in this animal model of ALS and perhaps patients with the disease.
NeuroReport, 2014
Human neural progenitor cells (hNPCs) derived from the fetal cortex can be expanded in vitro and ... more Human neural progenitor cells (hNPCs) derived from the fetal cortex can be expanded in vitro and genetically modified through lentiviral transduction to secrete growth factors shown to have a neurotrophic effect in animal models of neurological disease. hNPCs survive and mature following transplantation into the central nervous system of large and small animals including the rat model of amyotrophic lateral sclerosis. Here we report that hNPCs engineered to express glial cell line-derived neurotrophic factor (GDNF) survive long-term (7.5 months) following transplantation into the spinal cord of athymic nude rats and continue to secrete GDNF. Cell proliferation declined while the number of astrocytes increased, suggesting final maturation of the cells over time in vivo. Together these data show that GDNF-producing hNPCs may be useful as a source of cells for long-term delivery of both astrocytes and GDNF to the damaged central nervous system.
Journal of Comparative Neurology, 2014
Transplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace ... more Transplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace lost cells, modulate the injury environment, or create a permissive milieu to protect and regenerate host neurons is a promising therapeutic strategy for neurological diseases. Deriving NPCs from human fetal tissue is feasible, although problematic issues include limited sources and ethical concerns. Here we describe a new and abundant source of NPCs derived from human induced pluripotent stem cells (iPSCs). A novel chopping technique was used to transform adherent iPSCs into freefloating spheres that were easy to maintain and were expandable (EZ spheres) Stem Cell
American Journal of Respiratory and Critical Care Medicine, 2013
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 19, 2014
Recently, there has been remarkable progress in understanding inherited forms of ALS in which wel... more Recently, there has been remarkable progress in understanding inherited forms of ALS in which well defined mutations are known to cause the disease. Rodent models in which the superoxide dismutase-1 (SOD1) mutation is overexpressed recapitulate hallmark signs of ALS in patients. Early anatomical changes in mouse models of fALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction of toxic mutant SOD1 in the spinal cord and muscle of these models has beneficial effects. Therefore, much of ALS research has focused on spinal motor neuron and NMJ aspects of the disease. Here we show that, in the SOD1 G93A rat model of ALS, spinal motor neuron loss occurs presymptomatically and before degeneration of ventral root axons and denervation of NMJs. Although overt cell death of corticospinal motor neurons does not occur until disease endpoint, we wanted to establish whether the upper motor neuron might still play a critical role in disease progression. Surprisingly, the knockdown of mutant SOD1 in only the motor cortex of presymptomatic SOD1 G93A rats through targeted delivery of AAV9 -SOD1-shRNA resulted in a significant delay of disease onset, expansion of lifespan, enhanced survival of spinal motor neurons, and maintenance of NMJs. This datum suggests an early dysfunction and thus an important role of the upper motor neuron in this animal model of ALS and perhaps patients with the disease.
NeuroReport, 2014
Human neural progenitor cells (hNPCs) derived from the fetal cortex can be expanded in vitro and ... more Human neural progenitor cells (hNPCs) derived from the fetal cortex can be expanded in vitro and genetically modified through lentiviral transduction to secrete growth factors shown to have a neurotrophic effect in animal models of neurological disease. hNPCs survive and mature following transplantation into the central nervous system of large and small animals including the rat model of amyotrophic lateral sclerosis. Here we report that hNPCs engineered to express glial cell line-derived neurotrophic factor (GDNF) survive long-term (7.5 months) following transplantation into the spinal cord of athymic nude rats and continue to secrete GDNF. Cell proliferation declined while the number of astrocytes increased, suggesting final maturation of the cells over time in vivo. Together these data show that GDNF-producing hNPCs may be useful as a source of cells for long-term delivery of both astrocytes and GDNF to the damaged central nervous system.
Journal of Comparative Neurology, 2014
Transplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace ... more Transplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace lost cells, modulate the injury environment, or create a permissive milieu to protect and regenerate host neurons is a promising therapeutic strategy for neurological diseases. Deriving NPCs from human fetal tissue is feasible, although problematic issues include limited sources and ethical concerns. Here we describe a new and abundant source of NPCs derived from human induced pluripotent stem cells (iPSCs). A novel chopping technique was used to transform adherent iPSCs into freefloating spheres that were easy to maintain and were expandable (EZ spheres) Stem Cell
American Journal of Respiratory and Critical Care Medicine, 2013
Journal of Reconstructive Microsurgery, 2006
The search for better surgical repair of nerve injuries should be aimed at uncovering alternative... more The search for better surgical repair of nerve injuries should be aimed at uncovering alternatives that not only are efficient, but also enhance nerve growth. The purpose of this study was to compare functional nerve responses following repair with either a traditional microsuture technique or Quixil human fibrin sealant. Thirty female Lewis rats received transection of the right sciatic nerve. Nerve repair was achieved with either epineurial microsuture (n ¼ 15) or Quixil fibrin glue (n ¼ 15). Functional results were assessed at 2, 6, and 12 weeks postoperatively with walking-track analysis. Electrophysiologic nerve recordings were also performed 12 weeks postoperatively.
Journal of Reconstructive Microsurgery, 2006
The search for better surgical repair of nerve injuries should be aimed at uncovering alternative... more The search for better surgical repair of nerve injuries should be aimed at uncovering alternatives that not only are efficient, but also enhance nerve growth. The purpose of this study was to compare functional nerve responses following repair with either a traditional microsuture technique or Quixil human fibrin sealant. Thirty female Lewis rats received transection of the right sciatic nerve. Nerve repair was achieved with either epineurial microsuture (n ¼ 15) or Quixil fibrin glue (n ¼ 15). Functional results were assessed at 2, 6, and 12 weeks postoperatively with walking-track analysis. Electrophysiologic nerve recordings were also performed 12 weeks postoperatively.
Journal of Reconstructive Microsurgery, 2006
The search for better surgical repair of nerve injuries should be aimed at uncovering alternative... more The search for better surgical repair of nerve injuries should be aimed at uncovering alternatives that not only are efficient, but also enhance nerve growth. The purpose of this study was to compare functional nerve responses following repair with either a traditional microsuture technique or Quixil human fibrin sealant. Thirty female Lewis rats received transection of the right sciatic nerve. Nerve repair was achieved with either epineurial microsuture (n ¼ 15) or Quixil fibrin glue (n ¼ 15). Functional results were assessed at 2, 6, and 12 weeks postoperatively with walking-track analysis. Electrophysiologic nerve recordings were also performed 12 weeks postoperatively.
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 19, 2014
Recently, there has been remarkable progress in understanding inherited forms of ALS in which wel... more Recently, there has been remarkable progress in understanding inherited forms of ALS in which well defined mutations are known to cause the disease. Rodent models in which the superoxide dismutase-1 (SOD1) mutation is overexpressed recapitulate hallmark signs of ALS in patients. Early anatomical changes in mouse models of fALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction of toxic mutant SOD1 in the spinal cord and muscle of these models has beneficial effects. Therefore, much of ALS research has focused on spinal motor neuron and NMJ aspects of the disease. Here we show that, in the SOD1 G93A rat model of ALS, spinal motor neuron loss occurs presymptomatically and before degeneration of ventral root axons and denervation of NMJs. Although overt cell death of corticospinal motor neurons does not occur until disease endpoint, we wanted to establish whether the upper motor neuron might still play a critical role in disease progression. Surprisingly, the knockdown of mutant SOD1 in only the motor cortex of presymptomatic SOD1 G93A rats through targeted delivery of AAV9 -SOD1-shRNA resulted in a significant delay of disease onset, expansion of lifespan, enhanced survival of spinal motor neurons, and maintenance of NMJs. This datum suggests an early dysfunction and thus an important role of the upper motor neuron in this animal model of ALS and perhaps patients with the disease.
NeuroReport, 2014
Human neural progenitor cells (hNPCs) derived from the fetal cortex can be expanded in vitro and ... more Human neural progenitor cells (hNPCs) derived from the fetal cortex can be expanded in vitro and genetically modified through lentiviral transduction to secrete growth factors shown to have a neurotrophic effect in animal models of neurological disease. hNPCs survive and mature following transplantation into the central nervous system of large and small animals including the rat model of amyotrophic lateral sclerosis. Here we report that hNPCs engineered to express glial cell line-derived neurotrophic factor (GDNF) survive long-term (7.5 months) following transplantation into the spinal cord of athymic nude rats and continue to secrete GDNF. Cell proliferation declined while the number of astrocytes increased, suggesting final maturation of the cells over time in vivo. Together these data show that GDNF-producing hNPCs may be useful as a source of cells for long-term delivery of both astrocytes and GDNF to the damaged central nervous system.
Journal of Comparative Neurology, 2014
Transplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace ... more Transplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace lost cells, modulate the injury environment, or create a permissive milieu to protect and regenerate host neurons is a promising therapeutic strategy for neurological diseases. Deriving NPCs from human fetal tissue is feasible, although problematic issues include limited sources and ethical concerns. Here we describe a new and abundant source of NPCs derived from human induced pluripotent stem cells (iPSCs). A novel chopping technique was used to transform adherent iPSCs into freefloating spheres that were easy to maintain and were expandable (EZ spheres) Stem Cell
American Journal of Respiratory and Critical Care Medicine, 2013
The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 19, 2014
Recently, there has been remarkable progress in understanding inherited forms of ALS in which wel... more Recently, there has been remarkable progress in understanding inherited forms of ALS in which well defined mutations are known to cause the disease. Rodent models in which the superoxide dismutase-1 (SOD1) mutation is overexpressed recapitulate hallmark signs of ALS in patients. Early anatomical changes in mouse models of fALS are seen in the neuromuscular junctions (NMJs) and lower motor neurons, and selective reduction of toxic mutant SOD1 in the spinal cord and muscle of these models has beneficial effects. Therefore, much of ALS research has focused on spinal motor neuron and NMJ aspects of the disease. Here we show that, in the SOD1 G93A rat model of ALS, spinal motor neuron loss occurs presymptomatically and before degeneration of ventral root axons and denervation of NMJs. Although overt cell death of corticospinal motor neurons does not occur until disease endpoint, we wanted to establish whether the upper motor neuron might still play a critical role in disease progression. Surprisingly, the knockdown of mutant SOD1 in only the motor cortex of presymptomatic SOD1 G93A rats through targeted delivery of AAV9 -SOD1-shRNA resulted in a significant delay of disease onset, expansion of lifespan, enhanced survival of spinal motor neurons, and maintenance of NMJs. This datum suggests an early dysfunction and thus an important role of the upper motor neuron in this animal model of ALS and perhaps patients with the disease.
NeuroReport, 2014
Human neural progenitor cells (hNPCs) derived from the fetal cortex can be expanded in vitro and ... more Human neural progenitor cells (hNPCs) derived from the fetal cortex can be expanded in vitro and genetically modified through lentiviral transduction to secrete growth factors shown to have a neurotrophic effect in animal models of neurological disease. hNPCs survive and mature following transplantation into the central nervous system of large and small animals including the rat model of amyotrophic lateral sclerosis. Here we report that hNPCs engineered to express glial cell line-derived neurotrophic factor (GDNF) survive long-term (7.5 months) following transplantation into the spinal cord of athymic nude rats and continue to secrete GDNF. Cell proliferation declined while the number of astrocytes increased, suggesting final maturation of the cells over time in vivo. Together these data show that GDNF-producing hNPCs may be useful as a source of cells for long-term delivery of both astrocytes and GDNF to the damaged central nervous system.
Journal of Comparative Neurology, 2014
Transplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace ... more Transplantation of human neural progenitor cells (NPCs) into the brain or spinal cord to replace lost cells, modulate the injury environment, or create a permissive milieu to protect and regenerate host neurons is a promising therapeutic strategy for neurological diseases. Deriving NPCs from human fetal tissue is feasible, although problematic issues include limited sources and ethical concerns. Here we describe a new and abundant source of NPCs derived from human induced pluripotent stem cells (iPSCs). A novel chopping technique was used to transform adherent iPSCs into freefloating spheres that were easy to maintain and were expandable (EZ spheres) Stem Cell
American Journal of Respiratory and Critical Care Medicine, 2013
Journal of Reconstructive Microsurgery, 2006
The search for better surgical repair of nerve injuries should be aimed at uncovering alternative... more The search for better surgical repair of nerve injuries should be aimed at uncovering alternatives that not only are efficient, but also enhance nerve growth. The purpose of this study was to compare functional nerve responses following repair with either a traditional microsuture technique or Quixil human fibrin sealant. Thirty female Lewis rats received transection of the right sciatic nerve. Nerve repair was achieved with either epineurial microsuture (n ¼ 15) or Quixil fibrin glue (n ¼ 15). Functional results were assessed at 2, 6, and 12 weeks postoperatively with walking-track analysis. Electrophysiologic nerve recordings were also performed 12 weeks postoperatively.
Journal of Reconstructive Microsurgery, 2006
The search for better surgical repair of nerve injuries should be aimed at uncovering alternative... more The search for better surgical repair of nerve injuries should be aimed at uncovering alternatives that not only are efficient, but also enhance nerve growth. The purpose of this study was to compare functional nerve responses following repair with either a traditional microsuture technique or Quixil human fibrin sealant. Thirty female Lewis rats received transection of the right sciatic nerve. Nerve repair was achieved with either epineurial microsuture (n ¼ 15) or Quixil fibrin glue (n ¼ 15). Functional results were assessed at 2, 6, and 12 weeks postoperatively with walking-track analysis. Electrophysiologic nerve recordings were also performed 12 weeks postoperatively.
Journal of Reconstructive Microsurgery, 2006
The search for better surgical repair of nerve injuries should be aimed at uncovering alternative... more The search for better surgical repair of nerve injuries should be aimed at uncovering alternatives that not only are efficient, but also enhance nerve growth. The purpose of this study was to compare functional nerve responses following repair with either a traditional microsuture technique or Quixil human fibrin sealant. Thirty female Lewis rats received transection of the right sciatic nerve. Nerve repair was achieved with either epineurial microsuture (n ¼ 15) or Quixil fibrin glue (n ¼ 15). Functional results were assessed at 2, 6, and 12 weeks postoperatively with walking-track analysis. Electrophysiologic nerve recordings were also performed 12 weeks postoperatively.