Intra-arterial infusion of human bone marrow-derived mesenchymal stem cells results in transient localization in the brain after cerebral ischemia in rats

Mitkari, Bhimashankar; Kerkelä, Erja; Nystedt, Johanna; Korhonen, Matti; Mikkonen, Ville; Huhtala, Tuulia; Jolkkonen, Jukka

doi:10.1016/j.expneurol.2012.09.018

Cited by 71 publications

(67 citation statements)

References 27 publications

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“…Similar data were confirmed by many others suggesting that even following intra-arterial administration, MSCs poorly engraft in the brain following cerebral ischemia despite a significant functional recovery [113].…”

Section: Ischemic Strokesupporting

confidence: 87%

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

2015

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Section: Ischemic Strokesupporting

confidence: 87%

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

2015

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“…After a 60-minute occlusion period, the www.jcbfm.com filament was gently removed and the ECA was carefully closed by electrocoagulation, leaving a long ECA stump for cell infusion. 3 Total Infarct Volume Magnetic resonance imaging was performed on postoperative days 1 and 43 with a Bruker 7 T horizontal scanner (Bruker, Ettlingen, Germany) used for imaging. The ImageJ program was used to analyze infarct volumes from T2-weighted images.…”

Section: Transient Middle Cerebral Artery Occlusionmentioning

confidence: 99%

“…After a 60-minute occlusion period, the 1 filament was gently removed and the ECA was carefully closed by electrocoagulation, leaving a long ECA stump for cell infusion. 3 …”

Section: Transient Middle Cerebral Artery Occlusionmentioning

confidence: 99%

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Unexpected Complication in a Rat Stroke Model: Exacerbation of Secondary Pathology in the Thalamus by Subacute Intraarterial Administration of Human Bone Marrow-Derived Mesenchymal Stem Cells

Mitkari

Kerkelä

Nystedt

et al. 2015

J Cereb Blood Flow Metab

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This study examined whether human bone marrow mesenchymal stromal/stem cells (BMMSCs) could alleviate the secondary pathology in the thalamus after middle cerebral artery occlusion (MCAO) in rats. Atypical accumulation of both amyloid-β (Aβ) and calcium in the thalamus was significantly higher in rats receiving the BMMSCs infusion 48 hours after MCAO as compared with the vehicle MCAO group. The elevated Aβ/calcium accumulation correlated with the level of impaired sensorimotor function. Although secondary pathology in the thalamus seems to be rodent specific, it needs to be taken into account because it may impair long-term behavioral recovery and negate therapeutic treatment effects. Flow & Metabolism (2015) 35, 363-366; doi:10.1038/jcbfm.2014; published online 7 January 2015 Journal of Cerebral BloodKeywords: β-amyloid; calcium; cell therapy; cerebral ischemia; secondary pathology INTRODUCTION At present therapeutic options in stroke are extremely limited and thus much effort is being directed at developing innovative treatments, such as cell therapies. In particular, intravascular cell therapy is a promising approach for the treatment of stroke and is claimed to achieve an efficient and wide cell engraftment in case of large or multiple lesions. 1 Since it is relatively noninvasive, application of this approach would be feasible in stroke therapy.We have previously shown that intravenous infusion of human umbilical cord blood cells in rats after middle cerebral artery occlusion (MCAO) results in the accumulation of cells primarily in the lungs. 2 The lung entrapment can be circumvented by intraarterial cell infusion, which can target cells to the ischemic brain as shown by intraarterial infusion of human bone marrow-derived stem cells (BMMSCs). 3 The most effective therapeutic time window for intraarterial cell transplantation is not known. Acute cell infusion after stroke has been postulated to be neuroprotective, whereas cell delivery at later time points (424 hours) may enhance brain repair mechanisms. 4 Late cell delivery is also thought to target the delayed secondary degeneration occurring in remote areas of the brain such as the ventroposterolateral and ventroposteromedial thalamic nuclei. 5,6 In most animal models, the thalamus is spared from the acute ischemic damage but the region is affected because it has synaptic connections with the primary injury site. The widespread corticostriatal damage results in retrograde and anterograde degeneration, 7 which is also associated with atypical accumulation of amyloid precursor protein (APP) and amyloid-β (Aβ) in the thalamus. 6 The initially diffuse APP and Aβ staining becomes later transformed into dense plaque-like deposits in the thalamus. Interestingly, the APP/Aβ depositions show an overlapping distribution with calcium deposits. 8 The secondary pathology in the thalamus takes place in a delayed manner after the ischemic event and thus represents a novel target for stroke therapy. The aim of the present work was to study whether human BMMSCs (1 × 10 6 ...

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“…In spite of this, HSPC transplantation decreases the infarct size and reduces inflammation in the brain and the spleen of the treated animals [51]. Moreover, it has been observed that MSC only transiently engraft the ischemic brain after an intra-arterial infusion [52], and that systemically delivered UCB-MNCs promote the behavioral recovery in an animal model of stroke, despite the low engraftment level in the host brain [53]. In summary, MSCs, bone marrow MNCs (BM-MNCs), and UCB-MNCs can improve neurological function in several models of stroke, through a combination of effects, such as neuroprotection, immunomodulation, and stimulation of neural plasticity [54][55][56][57][58][59][60][61][62][63][64], but these effects are not necessarily due to the presence of the cells at the injury site.…”

Section: Non-nspcmentioning

confidence: 99%

The Rise of Cell Therapy Trials for Stroke: Review of Published and Registered Studies

Rosado-de-Castro

Pimentel‐Coelho

Fonseca

et al. 2013

Stem Cells and Development

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Stroke is the second leading cause of death and the third leading cause of disability worldwide. Approximately 16 million first-ever strokes occur each year, leading to nearly 6 million deaths. Nevertheless, currently, very few therapeutic options are available. Cell therapies have been applied successfully in different hematological diseases, and are currently being investigated for treating ischemic heart disease, with promising results. Recent preclinical studies have indicated that cell therapies may provide structural and functional benefits after stroke. However, the effects of these treatments are not yet fully understood and are the subject of continuing investigation. Meanwhile, different clinical trials for stroke, the majority of them small, nonrandomized, and uncontrolled, have been reported, and their results indicate that cell therapy seems safe and feasible in these conditions. In the last 2 years, the number of published and registered trials has dramatically increased. Here, we review the main findings available in the field, with emphasis on the clinical results. Moreover, we address some of the questions that have been raised to date, to improve future studies.

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Intra-arterial infusion of human bone marrow-derived mesenchymal stem cells results in transient localization in the brain after cerebral ischemia in rats

Cited by 71 publications

References 27 publications

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

Mesenchymal stem cells for the treatment of neurological diseases: Immunoregulation beyond neuroprotection

Unexpected Complication in a Rat Stroke Model: Exacerbation of Secondary Pathology in the Thalamus by Subacute Intraarterial Administration of Human Bone Marrow-Derived Mesenchymal Stem Cells

The Rise of Cell Therapy Trials for Stroke: Review of Published and Registered Studies

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