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Human motor neuron progenitor transplantation leads to endogenous neuronal sparing in 3 models of motor neuron loss.

Wyatt TJ, Rossi SL, Siegenthaler MM, Frame J, Robles R, Nistor G, Keirstead HS - Stem Cells Int (2011)

Bottom Line: In order to investigate the neurotrophic effects of a motor neuron lineage graft, we transplanted human embryonic stem cell-derived motor neuron progenitors (hMNPs) and examined their histopathological effect in three animal models of motor neuron loss.In addition, we have also found that hMNPs secrete physiologically active growth factors in vivo, including NGF and NT-3, which significantly enhanced the number of spared endogenous neurons in all three animal models.The ability to maintain dying motor neurons by delivering motor neuron-specific neurotrophic support represents a powerful treatment strategy for diseases characterized by motor neuron loss.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy & Neurobiology, Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, School of Medicine, 2002 Sue and Bill Gross Hall: A CIRM Institute, University of California at Irvine, Irvine, CA 92697-4292, USA.

ABSTRACT
Motor neuron loss is characteristic of many neurodegenerative disorders and results in rapid loss of muscle control, paralysis, and eventual death in severe cases. In order to investigate the neurotrophic effects of a motor neuron lineage graft, we transplanted human embryonic stem cell-derived motor neuron progenitors (hMNPs) and examined their histopathological effect in three animal models of motor neuron loss. Specifically, we transplanted hMNPs into rodent models of SMA (Δ7SMN), ALS (SOD1 G93A), and spinal cord injury (SCI). The transplanted cells survived and differentiated in all models. In addition, we have also found that hMNPs secrete physiologically active growth factors in vivo, including NGF and NT-3, which significantly enhanced the number of spared endogenous neurons in all three animal models. The ability to maintain dying motor neurons by delivering motor neuron-specific neurotrophic support represents a powerful treatment strategy for diseases characterized by motor neuron loss.

No MeSH data available.


Related in: MedlinePlus

hMNPs cause neurite branching in vitro. Neurite length was significantly longer (P < .05) in cortical neuron cultures exposed to hMNP-conditioned media (a) for 7 days as compared to cortical neuron cultures exposed to control MN differentiation media (b). (c) The length of neurites in cultures exposed to hMNPconditioned media as compared to those exposed to control media was significantly higher (P < .05). Bar = 50 μm.
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fig3: hMNPs cause neurite branching in vitro. Neurite length was significantly longer (P < .05) in cortical neuron cultures exposed to hMNP-conditioned media (a) for 7 days as compared to cortical neuron cultures exposed to control MN differentiation media (b). (c) The length of neurites in cultures exposed to hMNPconditioned media as compared to those exposed to control media was significantly higher (P < .05). Bar = 50 μm.

Mentions: Rossi et al [20] have previously shown that hMNP's secrete various growth factors. To investigate the neurotrophic potential of hMNP secretions, we performed functional assays of hMNP secretions on cortical neurons in vitro (Figure 3). Neurite length of cortical neuron cultures exposed to hMNP-conditioned media (Figure 3(a)) was compared to neurite length of cortical neuron cultures exposed to control MN differentiation media only (without conditioning) (Figure 3(b)) and was found to be significantly greater (P < .05; (Figure 3(c)). Neurite length of cortical neuron cultures exposed to hMNP-conditioned media was 250 μm ± 27 μm, and neurite length of cortical neuron cultures exposed to MN differentiation media only was 151 μm ± 32 μm.


Human motor neuron progenitor transplantation leads to endogenous neuronal sparing in 3 models of motor neuron loss.

Wyatt TJ, Rossi SL, Siegenthaler MM, Frame J, Robles R, Nistor G, Keirstead HS - Stem Cells Int (2011)

hMNPs cause neurite branching in vitro. Neurite length was significantly longer (P < .05) in cortical neuron cultures exposed to hMNP-conditioned media (a) for 7 days as compared to cortical neuron cultures exposed to control MN differentiation media (b). (c) The length of neurites in cultures exposed to hMNPconditioned media as compared to those exposed to control media was significantly higher (P < .05). Bar = 50 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig3: hMNPs cause neurite branching in vitro. Neurite length was significantly longer (P < .05) in cortical neuron cultures exposed to hMNP-conditioned media (a) for 7 days as compared to cortical neuron cultures exposed to control MN differentiation media (b). (c) The length of neurites in cultures exposed to hMNPconditioned media as compared to those exposed to control media was significantly higher (P < .05). Bar = 50 μm.
Mentions: Rossi et al [20] have previously shown that hMNP's secrete various growth factors. To investigate the neurotrophic potential of hMNP secretions, we performed functional assays of hMNP secretions on cortical neurons in vitro (Figure 3). Neurite length of cortical neuron cultures exposed to hMNP-conditioned media (Figure 3(a)) was compared to neurite length of cortical neuron cultures exposed to control MN differentiation media only (without conditioning) (Figure 3(b)) and was found to be significantly greater (P < .05; (Figure 3(c)). Neurite length of cortical neuron cultures exposed to hMNP-conditioned media was 250 μm ± 27 μm, and neurite length of cortical neuron cultures exposed to MN differentiation media only was 151 μm ± 32 μm.

Bottom Line: In order to investigate the neurotrophic effects of a motor neuron lineage graft, we transplanted human embryonic stem cell-derived motor neuron progenitors (hMNPs) and examined their histopathological effect in three animal models of motor neuron loss.In addition, we have also found that hMNPs secrete physiologically active growth factors in vivo, including NGF and NT-3, which significantly enhanced the number of spared endogenous neurons in all three animal models.The ability to maintain dying motor neurons by delivering motor neuron-specific neurotrophic support represents a powerful treatment strategy for diseases characterized by motor neuron loss.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy & Neurobiology, Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, School of Medicine, 2002 Sue and Bill Gross Hall: A CIRM Institute, University of California at Irvine, Irvine, CA 92697-4292, USA.

ABSTRACT
Motor neuron loss is characteristic of many neurodegenerative disorders and results in rapid loss of muscle control, paralysis, and eventual death in severe cases. In order to investigate the neurotrophic effects of a motor neuron lineage graft, we transplanted human embryonic stem cell-derived motor neuron progenitors (hMNPs) and examined their histopathological effect in three animal models of motor neuron loss. Specifically, we transplanted hMNPs into rodent models of SMA (Δ7SMN), ALS (SOD1 G93A), and spinal cord injury (SCI). The transplanted cells survived and differentiated in all models. In addition, we have also found that hMNPs secrete physiologically active growth factors in vivo, including NGF and NT-3, which significantly enhanced the number of spared endogenous neurons in all three animal models. The ability to maintain dying motor neurons by delivering motor neuron-specific neurotrophic support represents a powerful treatment strategy for diseases characterized by motor neuron loss.

No MeSH data available.


Related in: MedlinePlus