Positive Effect of Transplantation of hNT Neurons (NTera 2/D1 Cell-Line) in a Model of Familial Amyotrophic Lateral Sclerosis

Garbuzova‐Davis, Svitlana; Willing, Alison E.; Milliken, Melissa; Saporta, Samuel; Zigova, Tanya; Cahill, David W.; Sanberg, Paul R.

doi:10.1006/exnr.2002.7949

Cited by 20 publications

(27 citation statements)

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“…Other cell transplantation approaches that did not replace injured motor neurons, including those with enhanced growth factor expression, also showed some improvement in ALS models (Aebischer et al, 1996;Garbuzova-Davis et al, 2002, 2003Corti et al, 2004Corti et al, , 2007Llado et al, 2004;Yan et al, 2006;Martin and Liu, 2007). Moreover, administration of growth factors was reported to have some beneficial roles on disease outcome in ALS rodent models (Federici and Boulis, 2006).…”

Section: Discussionmentioning

confidence: 99%

Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice

et al. 2009

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Neural progenitor cells (NPs) have shown several promising benefits for the treatment of neurological disorders. To evaluate the therapeutic potential of human neural progenitor cells (hNPs) in amyotrophic lateral sclerosis (ALS), we transplanted hNPs or growth factor (GF)-expressing hNPs into the central nervous system (CNS) of mutant Cu/Zn superoxide dismutase (SOD1 G93A ) transgenic mice. The hNPs were engineered to express brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), VEGF, neurotrophin-3 (NT-3), or glial cell-derived neurotrophic factor (GDNF), respectively, by adenoviral vector and GDNF by lentiviral vector before transplantation. Donor-derived cells engrafted and migrated into the spinal cord or brain of ALS mice and differentiated into neurons, oligodendrocytes, or glutamate transporter-1 (GLT1)-expressing astrocytes while some cells retained immature markers. Transplantation of GDNF-or IGF-1-expressing hNPs attenuated the loss of motor neurons and induced trophic changes in motor neurons of the spinal cord. However, improvement in motor performance and extension of lifespan were not observed in all hNP transplantation groups compared to vehicle-injected controls. Moreover, the lifespan of GDNF-expressing hNP recipient mice by lentiviral vector was shortened compared to controls, which was largely due to the decreased survival times of female animals. These results imply that although implanted hNPs differentiate into GLT1-expressing astrocytes and secrete GFs, which maintain dying motor neurons, inadequate trophic support could be harmful and there is sexual dimorphism in response to GDNF delivery in ALS mice. Therefore, additional therapeutic approaches may be required for full functional recovery.

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Section: Discussionmentioning

confidence: 99%

Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice

et al. 2009

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“…MSCs transplantation into the spinal cord to ameliorate ALS (Mazzini et al, 2006) In a mouse model, neurons obtained from human NT-2 cell line (Garbuzova-Davis et al, 2002) and umbilical cord blood cells (Garbuzova-Davis et al, 2003) …”

Section: Amyotrophic Lateral Sclerosis (Als)mentioning

confidence: 99%

Resurrection of neurodegenerative diseases via stem cells

Nagaraj

2016

Biomed Res Ther

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Abstract-Neurodegenerative diseases (NDDs) are complex disorders that degenerates central nervous system. To this end, we have achieved only palliative treatments and their success is limited. Emerging studies suggest stem cells could be an alternative to recover lost neural network. Transplanting stem cells for replacing damaged neurons is a pivotal step in cell replacement therapies. In this article, NDDs and their pathology, current methods of combating NDDs and potentiality of stem cells in treating NDDs have been reviewed briefly. In addition to this , technical issues that hamper clinical applications of stem cells in creating cellular models and grafted cells for neuron resurrection have been discussed.

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“…Various cell transplantations have been performed on hSOD1-G93A rodent models. They include: i) human embryonic germ cell delivered to cerebral spinal fluid (Kerr et al, 2003); ii) human neural stem cells grafted into the spinal cord (Yan et al, 2006); iii) hNT neurons derived from a human teratocarcinoma cell line grafted into spinal cord (Garbuzova-Davis et al, 2002); mouse Sertoli cells into parenchyma (Hemendinger et al, 2005); and human umbilical cord blood cells transfused into the systemic circulation (Habisch et al, 2007). In each of the cases, there was some degree of positive effect on motor neuron survival and life span of the animals.…”

Section: Protective Effect Of Neural Stem Cell and Other Cells In Thementioning

confidence: 99%

Stem Cell Application for Amyotrophic Lateral Sclerosis: Growth Factor Delivery and Cell Therapy

Suzuki¹,

Tso²,

Meyer³

2012

Amyotrophic Lateral Sclerosis

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Positive Effect of Transplantation of hNT Neurons (NTera 2/D1 Cell-Line) in a Model of Familial Amyotrophic Lateral Sclerosis

Cited by 20 publications

References 0 publications

Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice

Growth factor-expressing human neural progenitor cell grafts protect motor neurons but do not ameliorate motor performance and survival in ALS mice

Resurrection of neurodegenerative diseases via stem cells

Stem Cell Application for Amyotrophic Lateral Sclerosis: Growth Factor Delivery and Cell Therapy

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