Treatment of stroke in rat with intracarotid administration of marrow stromal cells

Li, Y.; Chen, J.; Wang, L.; Lü, Mei; Chopp, Michael

doi:10.1212/wnl.56.12.1666

Cited by 400 publications

(281 citation statements)

References 46 publications

(35 reference statements)

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“…We also found on day 14 that the MSC-only treated group could significantly reduce the infarction volume under the superacute treatment compared with the PBS-treated group, but not under the acute treatment. This was the same as the Chopp's group had reported, that transplanted MSCs to the transient MCAO model 24 h after ischemia occurred had improved neurological function recovery, but not significantly decreased infarction area Li et al, 2000Li et al, , 2001, while our data of the superacute treatment showed the contrast result. We thought that it might have been caused by the different therapeutic time window.…”

Section: Discussionsupporting

confidence: 89%

Novel Therapeutic Strategy for Stroke in Rats by Bone Marrow Stromal Cells and ex vivo HGF Gene Transfer with HSV-1 Vector

Zhao

Nonoguchi

Ikeda

et al. 2006

J Cereb Blood Flow Metab

123

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Occlusive cerebrovascular disease leads to brain ischemia that causes neurological deficits. Here we introduce a new strategy combining mesenchymal stromal cells (MSCs) and ex vivo hepatocyte growth factor (HGF) gene transferring with a multimutated herpes simplex virus type-1 vector in a rat transient middle cerebral artery occlusion (MCAO) model. Gene-transferred MSCs were intracerebrally transplanted into the rats' ischemic brains at 2 h (superacute) or 24 h (acute) after MCAO. Behavioral tests showed significant improvement of neurological deficits in the HGF-transferred MSCs (MSC-HGF)-treated group compared with the phosphatebuffered saline (PBS)-treated and MSCs-only-treated group. The significant difference of infarction areas on day 3 was detected only between the MSC-HGF group and the PBS group with the superacute treatment, but was detected among each group on day 14 with both transplantations. After the superacute transplantation, we detected abundant expression of HGF protein in the ischemic brain of the MSC-HGF group compared with others on day 1 after treatment, and it was maintained for at least 2 weeks. Furthermore, we determined that the increased expression of HGF was derived from the transferred HGF gene in gene-modified MSCs. The percentage of apoptosis-positive cells in the ischemic boundary zone (IBZ) was significantly decreased, while that of remaining neurons in the cortex of the IBZ was significantly increased in the MSC-HGF group compared with others. The present study shows that combined therapy is more therapeutically efficient than MSC cell therapy alone, and it may extend the therapeutic time window from superacute to acute phase.

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Section: Discussionsupporting

confidence: 89%

Novel Therapeutic Strategy for Stroke in Rats by Bone Marrow Stromal Cells and ex vivo HGF Gene Transfer with HSV-1 Vector

Zhao

Nonoguchi

Ikeda

et al. 2006

J Cereb Blood Flow Metab

123

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show abstract

“…64 Neuroprotective effects were also observed by MSC infusion in animal models of stroke. 65 It is noteworthy that common paracrine mechanisms, independent of transdifferentiation, appear to support MSC therapeutic plasticity for a wide range of experimental diseases.…”

Section: Animal Models Of Tissue Protectionmentioning

confidence: 99%

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

Tyndall

Uccelli

2009

Bone Marrow Transplant

107

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“…cardiomyocytes [7][8][9], hepatocytes [10,11], and endothelial cells [12]. Especially, a large of body of evidence have indicated that mouse, rat, and human bone marrow MSCs can be induced to differentiate to neuron-like cells in culture [13][14][15][16] and further verified by the transplantation experiments in animal models of Parkinson's disease [17], stroke [18,19], cerebral ischemia [20], spinal cord injury [21], and Niemann-Pick disease [22]. However, despite many transplantation studies showing beneficial effects, most studies report low levels of cell persistence and neuronal differentiation in vivo.…”

Section: Introductionmentioning

confidence: 99%

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

et al. 2011

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Stem cell transplantation has been shown to improve functional outcome in degenerative and ischemic disorders. However, low in vivo survival and differentiation potential of the transplanted cells limits their overall effectiveness and thus clinical usage. Here we show that, after in vitro induction of neuronal differentiation and dedifferentiation, on withdrawal of extrinsic factors, mesenchymal stem cells (MSCs) derived from bone marrow, which have already committed to neuronal lineage, revert to a primitive cell population (dedifferentiated MSCs) retaining stem cell characteristics but exhibiting a reprogrammed phenotype distinct from their original counterparts. Of therapeutic interest, the dedifferentiated MSCs exhibited enhanced cell survival and higher efficacy in neuronal differentiation compared to unmanipulated MSCs both in vitro and in vivo, with significantly improved cognition function in a neonatal hypoxic-ischemic brain damage rat model. Increased expression of bcl-2 family proteins and micro-RNA-34a appears to be the important mechanism giving rise to this previously undefined stem cell population that may provide a novel treatment strategy with improved therapeutic efficacy.

show abstract

Treatment of stroke in rat with intracarotid administration of marrow stromal cells

Abstract: MSC injected intra-arterially are localized and directed to the territory of the middle cerebral artery, and these cells foster functional improvement after cerebral ischemia.

Cited by 400 publications

References 46 publications

Novel Therapeutic Strategy for Stroke in Rats by Bone Marrow Stromal Cells and ex vivo HGF Gene Transfer with HSV-1 Vector

Novel Therapeutic Strategy for Stroke in Rats by Bone Marrow Stromal Cells and ex vivo HGF Gene Transfer with HSV-1 Vector

Multipotent mesenchymal stromal cells for autoimmune diseases: teaching new dogs old tricks

Dedifferentiation-Reprogrammed Mesenchymal Stem Cells with Improved Therapeutic Potential

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