Recovery of spatial learning by grafts of a conditionally immortalized hippocampal neuroepithelial cell line into the ischaemia-lesioned hippocampus

Sinden, John D.; Rashid‐Doubell, Fiza; Kershaw, T. R.; Nelson, Aimee J.; Chadwick, Andrew; Jat, Parmjit; Noble, Mark; Hodges, Helen; Gray, Jeffrey A.

doi:10.1016/s0306-4522(97)00330-8

Cited by 153 publications

(95 citation statements)

References 27 publications

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“…It has been reported that transplantation of other cell sources such as rodent embryonic hippocampal formation cells (37,39), MHP36, a conditionally immortal neuroepithelial stem cell line derived from embryonic mouse (53), and human neuroteratocarcinomaderived neurons (7,50,28) ameliorated neurological deficits induced by brain ischemia. Here we demonstrated that human bone marrow mesenchymal stem cells could engraft and reduce neurological deficits in a rat model of stroke.…”

Section: Discussionmentioning

confidence: 99%

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

Zhao

Duan

Reyes

et al. 2002

Experimental Neurology

758

468

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There is now evidence to suggest that bone marrow mesenchymal stem cells (MSCs) not only differentiate into mesodermal cells, but can also adopt the fate of endodermal and ectodermal cell types. In this study, we addressed the hypotheses that human MSCs can differentiate into neural cells when implanted in the brain and restore sensorimotor function after experimental stroke. Purified human MSCs were grafted into the cortex surrounding the area of infarction 1 week after cortical brain ischemia in rats. Two and 6 weeks after transplantation animals were assessed for sensorimotor function and then sacrificed for histological examination. Ischemic rats that received human MSCs exhibited significantly improved functional performance in limb placement test. Histological analyses revealed that transplanted human MSCs expressed markers for astrocytes (GFAP ؉ ), oligodendroglia (GalC ؉ ), and neurons (␤III ؉ , NF160 ؉ , NF200 ؉ , hNSE ؉ , and hNF70 ؉ ). The morphological features of the grafted cells, however, were spherical in nature with few processes. Therefore, it is unlikely that the functional recovery observed by the ischemic rats with human MSC grafts was mediated by the integration of new "neuronal" cells into the circuitry of the host brain. The observed functional improvement might have been mediated by proteins secreted by transplanted hMSCs, which could have upregulated host brain plasticity in response to experimental stroke.

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Section: Discussionmentioning

confidence: 99%

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

Zhao

Duan

Reyes

et al. 2002

Experimental Neurology

758

468

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“…64 Tate and coworkers 70 reported that NSCs survived in the injured brain and migrated to the fimbria hippocampus within 3 months of implantation but that, in the presence of a fibronectin matrix, increased cell survival and migration were noted. Neural stem cells derived from embryonic or neonatal rodent brains have been conditionally immortalized 54,66 or altered by retroviral vector-mediated transduction of an oncogene 58 and have subsequently shown the ability to develop phenotypic characteristics of native neural cells in vivo. The degree of injury may be important in cell survival, as recent work has revealed that transplanted NSCs may survive better after mild TBI than after severe TBI.…”

Section: Neural Stem Cell Therapymentioning

confidence: 99%

Cell therapies for traumatic brain injury

Harting

Baumgartner

Worth

et al. 2008

FOC

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Preliminary discoveries of the efficacy of cell therapy are currently being translated to clinical trials. Whereas a significant amount of work has been focused on cell therapy applications for a wide array of diseases, including cardiac disease, bone disease, hepatic disease, and cancer, there continues to be extraordinary anticipation that stem cells will advance the current therapeutic regimen for acute neurological disease. Traumatic brain injury is a devastating event for which current therapies are limited. In this report the authors discuss the current status of using adult stem cells to treat traumatic brain injury, including the basic cell types and potential mechanisms of action, preclinical data, and the initiation of clinical trials.

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“…Sinden et al (1997) demonstrated the recovery of spatial learning in ischemic rats following transplantation of MHP36 cell lines into the damaged CA1 regions. Wong, Hodges, and Horsburgh (2005) demonstrated a reduction of ischemic damages in the caudate nucleus following transplantation of MHP36 cell lines.…”

mentioning

confidence: 98%

Transplantation of hippocampal cell lines restore spatial learning in rats with ventral subicular lesions.

Jinkala¹,

Chakravarthy²,

Veena³

et al. 2009

Behavioral Neuroscience

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We have demonstrated in our previous studies that ventral subicular lesion induces neurodegeneration of the hippocampus and produces cognitive impairment in rats. In the present study, the efficacy of transplanted green fluorescent protein (GFP)-labeled hippocampal cell line (H3-GFP) cells in establishing functional recovery in ventral subicular lesioned rats has been evaluated. The survival of H3-GFP transplants and their ability to express trophic factors in vivo were also investigated. Adult male Wistar rats were subjected to selective lesioning of ventral subiculum and were transplanted with H3-GFP cells into the cornu ammonis 1 (CA1) hippocampus. The transplants settled mainly in the dentate gyrus and expressed neurotrophic factors, brain-derived neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF). The ventral subicular lesioned (VSL) rats with H3-GFP transplants showed enhanced expression of BDNF in the hippocampus and performed well in eight-arm radial maze and Morris water maze tasks. The VSL rats without hippocampal transplants continued to show cognitive impairment in task learning. The present study demonstrated the H3-GFP transplants mediated recovery of cognitive functions in VSL rats. Our study supports the notion of graft meditated host regeneration and functional recovery through trophic support, although these mechanisms require further investigation.

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Recovery of spatial learning by grafts of a conditionally immortalized hippocampal neuroepithelial cell line into the ischaemia-lesioned hippocampus

Cited by 153 publications

References 27 publications

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

Human Bone Marrow Stem Cells Exhibit Neural Phenotypes and Ameliorate Neurological Deficits after Grafting into the Ischemic Brain of Rats

Cell therapies for traumatic brain injury

Transplantation of hippocampal cell lines restore spatial learning in rats with ventral subicular lesions.

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