Transplantation of cultured human neuronal cells for patients with stroke

Kondziolka, Douglas; Wechsler, Lawrence R.; Goldstein, Steven; Meltzer, Carolyn C.; Thulborn, Keith R.; Gebel, James; Jannetta, Peter J.; DeCesare, Sharon; Elder, Elaine M.; McGrogan, Michael; Reitman, M. A.; Bynum, Lincoln J.

doi:10.1212/wnl.55.4.565

Cited by 584 publications

(364 citation statements)

References 11 publications

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“…These data strongly suggest that neovascularization is essential for neuronal regeneration after stroke and that therapeutic neovascularization is a potentially effective means of enhancing functional recovery. Our observations might explain the mild therapeutic effect achieved by neuronal cell transplantation after stroke reported in humans (38). This leads to the hypothesis that therapeutic neovascularization may be required to achieve optimal "take" of transplanted neuronal precursors in the setting of ischemia.…”

Section: Discussionsupporting

confidence: 52%

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

Taguchi¹,

Soma²,

Tanaka³

et al. 2004

J. Clin. Invest.

336

281

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Thrombo-occlusive cerebrovascular disease resulting in stroke and permanent neuronal loss is an important cause of morbidity and mortality. Because of the unique properties of cerebral vasculature and the limited reparative capability of neuronal tissue, it has been difficult to devise effective neuroprotective therapies in cerebral ischemia. Our results demonstrate that systemic administration of human cord blood-derived CD34 + cells to immunocompromised mice subjected to stroke 48 hours earlier induces neovascularization in the ischemic zone and provides a favorable environment for neuronal regeneration. Endogenous neurogenesis, suppressed by an antiangiogenic agent, is accelerated as a result of enhanced migration of neuronal progenitor cells to the damaged area, followed by their maturation and functional recovery. Our data suggest an essential role for CD34 + cells in promoting directly or indirectly an environment conducive to neovascularization of ischemic brain so that neuronal regeneration can proceed.

show abstract

Section: Discussionsupporting

confidence: 52%

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

Taguchi¹,

Soma²,

Tanaka³

et al. 2004

J. Clin. Invest.

336

281

View full text Add to dashboard Cite

show abstract

“…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

763

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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“…In most cases some index of behavioral function has been improved. hNT cells have also been used in clinical trials, and preliminary observations suggest that cell transplantation may be a viable stroke therapy (2,13).…”

mentioning

confidence: 99%

Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex

Kelly

Bliss

Shah

et al. 2004

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

571

446

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We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances (Ϸ1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker ␤-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.

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Transplantation of cultured human neuronal cells for patients with stroke

Cited by 584 publications

References 11 publications

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesisin a mouse model

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

Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex

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