Transplantation of Cryopreserved Human Embryonal Carcinoma-Derived Neurons (NT2N Cells) Promotes Functional Recovery in Ischemic Rats

Borlongan, Cesario V.; Tajima, Yasuo; Trojanowski, John Q.; Lee, Virginia M.‐Y.; Sanberg, Paul R.

doi:10.1006/exnr.1997.6730

Cited by 348 publications

(220 citation statements)

References 51 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

755

467

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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

755

467

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show abstract

“…When transplanted into an ischemic stroke model in the rat, hNT neurons restored mental function and limb usage (4). Recently, hNT neurons (designated as LBS to signify they were manufactured for human transplant use) were trans planted into a human patient who had suffered a throm botic stroke 6 months prior to the transplant.…”

Section: Discussionmentioning

confidence: 99%

Neural Transplantation of hNT Neurons for Huntington's Disease

et al. 1999

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Fetal striatal tissue transplants have been shown to restore motor deficits in rat and monkey models of Huntington's disease (HD). In the present study, using rats with unilateral striatal lesions, we compared fetal striatal tissue transplants to transplants of human NT (hNT) neurons. hNT neurons are terminally differentiated cells derived from the human NTera-2 cell line. In vitro, we have found that purified hNT neurons have a biochemical phenotype similar to that of human fetal striatal tissue. Both hNT neurons and fetal striatal tissue express mRNAs for glutamic acid decarboxylase, choline acetyltransferase, and the D1 and D2 dopamine receptors. Grafts of either hNT neurons or fetal striatal tissue into unilateral quinolinic acid-lesioned rat striatum improved methamphetamine-induced circling behavior. Sham controls showed no changes in methamphetamine-induced circling behavior. In the staircase test for skilled forelimb use, both transplant groups showed partial recovery in skilled use of the paw contralateral to the side of lesion, whereas the control animals showed continued deficits. These findings suggest that transplantation of hNT neurons may be an alternative to transplantation of fetal striatal tissue in the treatment of HD.

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“…Under equithesin (3 ml/kg i.p.) anesthesia (animals checked for pain reflexes), the animals were implanted with MultiStem either directly into the striatum (0.5 mm anterior to bregma, 2.8 mm lateral to midline and 5.0 mm below the dural surface) using a 28-gauge implantation cannula (Borlongan et al 1998c;Borlongan et al 1998d). Cells were thawed just prior to transplantation surgery as described in section 4.2 above.…”

Section: Multistem Transplantation (Ic and Iv)mentioning

confidence: 99%

Development of an allogeneic adherent stem cell therapy for treatment of ischemic stroke

Mays¹,

Borlongan²,

Yasuhara³

et al. 2010

J Exp Stroke Transl Med

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Transplantation of Cryopreserved Human Embryonal Carcinoma-Derived Neurons (NT2N Cells) Promotes Functional Recovery in Ischemic Rats

Cited by 348 publications

References 51 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

Neural Transplantation of hNT Neurons for Huntington's Disease

Development of an allogeneic adherent stem cell therapy for treatment of ischemic stroke

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