Foetal grafts from hippocampal regio superior alleviate ischaemic-induced behavioral deficits

Netto, Carlos Alexandre; Hodges, Helen; Sinden, John D.; LePeillet, Eliane; Kershaw, T. R.; Sowiński, P.; Meldrum, Brian S.; Gray, Jeffrey A.

doi:10.1016/0166-4328(93)90095-8

Cited by 26 publications

(14 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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

View full text Add to dashboard Cite

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.

show abstract

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

View full text Add to dashboard Cite

show abstract

“…Significantly, repair as assessed anatomically, electrophysiologically and behaviourally [138,139] appeared to be dependent on implantation of the specific, appropriate region of developing hippocampus (e.g., CA1 lesion repaired by CA1 not CA3). Such observations suggest a highly specific pattern of differentiation and connectivity would be required for NSCs to produce functional benefit in this model.…”

Section: Cerebral Ischaemiamentioning

confidence: 96%

Stem cell transplantation as an approach to brain repair

Armstrong¹,

Jain²,

Barker³

2001

Expert Opinion on Therapeutic Patents

View full text Add to dashboard Cite

“…[31] Fetal grafts from various neural structures were placed in the damaged adult rat hippocampus. Improvements in water maze testing were noted only in those animals receiving grafts that included the fetal CA1 region.…”

Section: Neural Transplantation To Improve Functionmentioning

confidence: 99%

“…Because the cognitive deficits present after fluid-percussion brain injury appear to relate to hippocampal cell loss, [18,44] transplants of hippocampal cells (or less-differentiated stem cells) rather than cortical cells may have resulted in further improvements. [7,20,26,31,39,49,[54][55][56]58] Future studies will examine this hypothesis.Neurological motor function in brain-injured animals receiving fetal transplants was significantly improved compared with control animals. To our knowledge, this is the first study to demonstrate such an effect in an experimental model of traumatic brain injury.…”

mentioning

confidence: 99%

Combined fetal neural transplantation and nerve growth factor infusion: effects on neurological outcome following fluid-percussion brain injury in the rat

Sinson¹,

Voddi²,

McIntosh³

1999

FOC

View full text Add to dashboard Cite

This study was designed to evaluate the histological and behavioral impact of fetal neural transplantation with and without neurotrophin infusion in rats subjected to traumatic brain injury using a clinically relevant model of lateral fluid-percussion brain injury. Adult male Sprague-Dawley rats received lateral fluid-percussion brain injury of moderate severity (2.1-2.3 atm). Twenty-four hours after injury, minced fetal cortical grafts (E16) were stereotactically transplanted into the site of injury cavity formation (in 32 rats). Ten control animals received injections of saline. A third group of 29 animals that received transplants also underwent placement of a miniosmotic pump (immediately after transplantation) to continuously infuse nerve growth factor (NGF) directly into the region of graft placement for the duration of the experiment. A fourth group of eight animals underwent transplantation of fetal cortical cells that had been dissociated and placed in suspension. Animals were evaluated at 72 hours, 1 week, and 2 weeks after injury for cognitive function (using the Morris water maze), posttraumatic motor dysfunction, and transplant survival and morphology (using Nissl and modified Palmgren's silver staining techniques). Robust survival of whole-tissue transplants was seen in 65.6% of animals and was not increased in animals receiving NGF infusion. Animals receiving transplants of cell suspension had no surviving grafts. Brain-injured animals receiving transplants showed significant cognitive improvements compared with controls at the 2-week evaluation. Significantly improved memory scores were seen at all evaluation times in animals receiving both NGF and transplants compared with injured controls and compared with animals receiving transplants alone at the 72-hour and 1-week evaluations. Neurological motor function scores were significantly improved in animals receiving transplants alone and those receiving transplants with NGF infusion. Histological evaluation demonstrated differentiation of grafted cells, decreased glial scarring around transplants when compared with control animals, and the presence of neuronal fibers bridging the interface between graft and host. This study demonstrates that fetal cortical cells transplanted into the injured cortex of the adult rat can improve both posttraumatic cognitive and motor function and interact with the injured host brain.

show abstract

Foetal grafts from hippocampal regio superior alleviate ischaemic-induced behavioral deficits

Cited by 26 publications

References 19 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 transplantation as an approach to brain repair

Combined fetal neural transplantation and nerve growth factor infusion: effects on neurological outcome following fluid-percussion brain injury in the rat

Contact Info

Product

Resources

About