Human neural stem cells improve cognitive function of aged brain

Qu, Tingyu; Brannen, Christopher L.; Kim, H M; Sugaya, Kimio

doi:10.1097/00001756-200105080-00016

Cited by 89 publications

(71 citation statements)

References 23 publications

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“…66 More specifically, stem cell engraftment to the hippocampus has resulted in increased neurogenesis in the dentate gyrus and improvement of cognitive impairment in prenatally heroin-exposed mice and in models of Alzheimer's disease. 22,23,67,68 Nevertheless, this study shows the effect of stem cells on depressive-like behavior for the first time.…”

Section: Discussionmentioning

confidence: 66%

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

et al. 2009

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Adult bone marrow-derived mesenchymal stem cells (MSCs) are regarded as potential candidates for treatment of neurodegenerative disorders, because of their ability to promote neurogenesis. MSCs promote neurogenesis by differentiating into neural lineages as well as by expressing neurotrophic factors that enhance the survival and differentiation of neural progenitor cells. Depression has been associated with impaired neurogenesis in the hippocampus and dentate gyrus. Therefore, the aim of this study was to analyze the therapeutic potential of MSCs in the Flinders sensitive line (FSL), a rat animal model for depression. Rats received an intracerebroventricular injection of culture-expanded and 1,1 0 -dioctadecyl-3,3,3 0 ,3 0 -tetramethylindocarbocyanine perchlorate (DiI)-labeled bone marrow-derived MSCs (10 5 cells). MSC-transplanted FSL rats showed significant improvement in their behavioral performance, as measured by the forced swim test and the dominant-submissive relationship (DSR) paradigm. After transplantation, MSCs migrated mainly to the ipsilateral dentate gyrus, CA1 and CA3 regions of the hippocampus, and to a lesser extent to the thalamus, hypothalamus, cortex and contralateral hippocampus. Neurogenesis was increased in the ipsilateral dentate gyrus and hippocampus of engrafted rats (granular cell layer) and was correlated with MSC engraftment and behavioral performance. We therefore postulate that MSCs may serve as a novel modality for treating depressive disorders.

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Section: Discussionmentioning

confidence: 66%

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

et al. 2009

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“…Previously, we showed that human NSCs (HNSCs) transplanted into aged rats differentiated into neural cells and could reverse age-associated cognitive impairment in these animals (3). This study demonstrated that the aged rat brain was capable of providing necessary environmental conditions for HNSCs to retain their multipotency and provided some evidence for the potential of stem cell replacement therapies to improve memory and cognitive deficits in AD.…”

mentioning

confidence: 72%

“…T ransplantation of neural stem cells (NSCs) to the developing brain and in animal models of neurodegeneration has demonstrated that migration and differentiation of these cells is regulated primarily by environmental cues (1)(2)(3)(4). Pathological changes that occur in neurodegenerative disorders such as Alzheimer's disease (AD) may profoundly affect the brain microenvironment, which may in turn affect the fate of NSCs.…”

mentioning

confidence: 99%

Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine

Marutle

Ohmitsu

Nilbratt

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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In a previous study, we found that human neural stem cells (HNSCs) exposed to high concentrations of secreted amyloid-precursor protein (sAPP) in vitro differentiated into mainly astrocytes, suggesting that pathological alterations in APP processing during neurodegenerative conditions such as Alzheimer's disease (AD) may prevent neuronal differentiation of HNSCs. Thus, successful neuroplacement therapy for AD may require regulating APP expression to favorable levels to enhance neuronal differentiation of HNSCs. Phenserine, a recently developed cholinesterase inhibitor (ChEI), has been reported to reduce APP levels in vitro and in vivo. amyloid precursor protein ͉ transplantation ͉ immunohistochemistry ͉ neurogenesis ͉ Alzheimer's disease T ransplantation of neural stem cells (NSCs) to the developing brain and in animal models of neurodegeneration has demonstrated that migration and differentiation of these cells is regulated primarily by environmental cues (1-4). Pathological changes that occur in neurodegenerative disorders such as Alzheimer's disease (AD) may profoundly affect the brain microenvironment, which may in turn affect the fate of NSCs.The amyloid hypothesis, which postulates that ␤-amyloid (A␤) neurotoxicity plays a causative role in AD, has dominated much of AD research (5) and the absence of a lethal phenotype in amyloid-precursor protein (APP) knockout mice (6) has detracted attention from the physiological functions of APP. Several studies have shown that APP is involved in regulating neurite outgrowth, cell proliferation, neuronal migration, and differentiation (7-10). APP expression is also increased after brain injury, and increased levels are observed in apoptotic cells (11,12). Other studies report that A␤ inhibits NSC migration by increasing amyloid-associated cell death and by dysregulation of cellular calcium homeostasis (13,14). These findings suggest that not only A␤ but that also altered APP processing during the course of AD may have effects on stem cell biology.Previously, we showed that human NSCs (HNSCs) transplanted into aged rats differentiated into neural cells and could reverse age-associated cognitive impairment in these animals (3). This study demonstrated that the aged rat brain was capable of providing necessary environmental conditions for HNSCs to retain their multipotency and provided some evidence for the potential of stem cell replacement therapies to improve memory and cognitive deficits in AD. However, we recently found increased in vitro glial differentiation of HNSCs treated with high doses of secreted APP or transfected with wild-type APP (15). This finding suggests that stem cell replacement approaches would have reduced effectiveness in the AD brain, in which impaired APP metabolism would prevent or reduce neuronal differentiation of implanted cells. Therefore, we suggest that regulation of APP levels in the brain is necessary for implementing neuroplacement strategies.(Ϫ)-Phenserine is a recently developed cholinesterase inhibitor (ChEI) currently in clinical ...

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“…Transplantation of stem cells has been attempted in rodent models of disease [103][104][105] with some degree of success, showing benefit to the animals receiving stem cell transplantation. In both rodents and primates with damage to the hippocampus, functional recovery was seen after transplantation of both fetal and immortalized neuroepithelial stem cells.…”

Section: Antiinflammatory Treatment Strategiesmentioning

confidence: 99%

Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here

Tobin

Bonds

Minshall

et al. 2014

J Cereb Blood Flow Metab

303

236

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This review covers the pathogenesis of ischemic stroke and future directions regarding therapeutic options after injury. Ischemic stroke is a devastating disease process affecting millions of people worldwide every year. The mechanisms underlying the pathophysiology of stroke are not fully understood but there is increasing evidence demonstrating the contribution of inflammation to the drastic changes after cerebral ischemia. This inflammation not only immediately affects the infarcted tissue but also causes long-term damage in the ischemic penumbra. Furthermore, the interaction between inflammation and subsequent neurogenesis is not well understood but the close relationship between these two processes has garnered significant interest in the last decade or so. Current approved therapy for stroke involving pharmacological thrombolysis is limited in its efficacy and new treatment strategies need to be investigated. Research aimed at new therapies is largely about transplantation of neural stem cells and using endogenous progenitor cells to promote brain repair. By understanding the interaction between inflammation and neurogenesis, new potential therapies could be developed to further establish brain repair mechanisms.

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Human neural stem cells improve cognitive function of aged brain

Cited by 89 publications

References 23 publications

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

Mesenchymal stem cells increase hippocampal neurogenesis and counteract depressive-like behavior

Modulation of human neural stem cell differentiation in Alzheimer (APP23) transgenic mice by phenserine

Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here

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