Transplantation of human fetal striatum into a rodent model of Huntington's disease ameliorates locomotor deficits

Pundt, Lisa L.; Kondoh, Takeshi; Conrad, John A.; Low, Walter C.

doi:10.1016/0168-0102(95)01009-2

Cited by 26 publications

(17 citation statements)

References 16 publications

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“…In contrast, a study that purified murine MSCs labeled with BrdU and then transplanted into lateral ventricle of neonatal mice (29) showed donor-derived mature astrocytes in host brain 12 days postgrafting. The differences between the morphological features in the grafted cells of the present study and those of Kopen et al (29) may be due to differences in the donor species, since it has been demonstrated that differentiation of human fetal brain cells is significantly slower after transplantation in comparison to fetal rodent brain cells (9,45). Another difference is that the transplant recipients used in the present study were adult rats while those used by Kopen et al (29) were neonatal mice.…”

Section: Discussioncontrasting

confidence: 61%

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

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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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Section: Discussioncontrasting

confidence: 61%

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

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763

468

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“…Transplantation of fetal striatum into animal models of Huntington's disease has shown to reverse behavioral defects [65]. Furthermore, primate studies have shown that fetal grafts may extend to cognitive function improvement as well [66].…”

Section: Stem Cell Therapy For Other Neurodegenerative Diseasesmentioning

confidence: 99%

Stem cell therapy for central nervous system demyelinating disease

Manganas

Maletić-Savatić

2005

Curr Neurol Neurosci Rep

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Recent advances in cell-based therapies for demyelinating central nervous system diseases have demonstrated the ability to restore damaged neuronal architecture and function. Demyelinated axons in patients with multiple sclerosis can spontaneously remyelinate over time; however, the rate and extent at which remyelination occurs is inadequate for complete recovery. Previous attempts aimed at regenerating myelin-forming cells have been successful but limited by the multifocal nature of the lesions and the inability to produce large numbers of myelin-producing cells in culture. Stem cell-based therapy can overcome these limitations to some extent and may prove useful in the future treatment of demyelinating diseases.

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“…In the studies of human foetal tissue transplants in animal models described above, the behavioural effects reported have been limited to drug-induced rotations, vibrissae-evoked touch test and adjusting steps test, and so far no effect has been reported on the paw-reaching test [35][36][37][38]. However, to date, neither the approach of additional training to allow transplanted animals to re-learn a task post-transplantation, and learn to use the graft, nor the environmental enrichment strategy has been applied to human foetal striatal transplant studies.…”

Section: What Do We Still Need To Know About Human Foetal Wge In Ordementioning

confidence: 99%

“…This has not been systematically investigated to date in any one, single study for human foetal samples. Thus, it is necessary to draw what we can from the published literature in which a range of ages from 6-to 14-week gestation has been used [35][36][37][38]. It has been shown that human foetal WGE cells harvested at 7-to 9-week post-conception [37] and also at 14-week post-conception [36] are able to ameliorate the apomorphine-induced deficits seen in animals having received unilateral excitotoxic striatal lesions, which mimic the pattern of cell loss seen in HD.…”

Section: What Do We Still Need To Know About Human Foetal Wge In Ordementioning

confidence: 99%

“…It is critical that the questions raised above are not dismissed as new cell sources are investigated, and one key step in preclinical validation of these alternatives will be to compare them to primary foetal tissue transplants. One important consideration relates to the functional readout from such studies, especially given the limited data thus far generated from transplants of human foetal tissue [35][36][37][38]; some rodent studies have highlighted the plasticity of striatal grafts, which can have implications on functional effects post-transplantation [40][41][42][43][44]. It has been shown that animals post-transplantation need to 're-learn' a task that had been well established prior to induction of the lesion, using the 9-hole box operant chamber [40].…”

Section: What Do We Still Need To Know About Human Foetal Wge In Ordementioning

confidence: 99%

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Transplantation in HD: Are We Transplanting the Right Cells?

Precious¹,

Kelly²

2017

Huntington's Disease - Molecular Pathogenesis and Current Models

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Cell replacement therapy is a viable option for the treatment of Huntington's disease (HD), where the aim is to replace the lost medium spiny projection neurons of the striatum. The intra-striatal engraftment of developing striatal precursors harvested from the foetal brain has provided proof of concept in both rodent models and human patients that these primary foetal tissue grafts can bring about a degree of functional recovery in a HDdegenerated brain. With the advent of pluripotent stem cell technologies, novel, potential alternative donor cell sources have become available. Ongoing studies are assessing the capacity of these cells to differentiate towards striatal precursors for transplantation in HD. Here, we review the characteristics of potential donor cells for HD with respect to available cell markers, functional properties and maturity of cells upon transplantation. We consider the optimal composition of the donor cell population, that is, whether a heterogeneous population containing all cell types from the developing striatum (the whole ganglionic eminence) is preferable to a more homogeneous population of striatal projection neurons, as directed by differentiation protocols applied to pluripotent stem cells. Furthermore, we consider what might be required to improve transplant efficacy and success, with respect to striatal differentiation of transplanted cells and functional improvement.

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Transplantation of human fetal striatum into a rodent model of Huntington's disease ameliorates locomotor deficits

Cited by 26 publications

References 16 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

Stem cell therapy for central nervous system demyelinating disease

Transplantation in HD: Are We Transplanting the Right Cells?

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