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Age of donor of human mesenchymal stem cells affects structural and functional recovery after cell therapy following ischaemic stroke.

ABSTRACT: Cell transplantation therapy offers great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is unclear. We investigated the regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischaemic stroke. The quantities of human mesenchymal stem cell (hMSC) secreted brain-derived neurotrophic factor in vitro and of monocyte chemotactic protein-1 at day 7 in vivo were both significantly higher for young hMSC compared with old hMSC. Male Sprague-Dawley rats subjected to transient middle cerebral artery occlusion that received young hMSC (trans-arterially at 24?h after stroke) showed better behavioural recovery with prevention of brain atrophy compared with rats that received old hMSC. Histological analysis of the peri-infarct cortex showed that rats treated with young hMSC had significantly fewer microglia and more vessels covered with pericytes. Interestingly, migration of neural stem/progenitor cells expressing Musashi-1 positively correlated with astrocyte process alignment, which was more pronounced for young hMSC. Aging of hMSC may be a critical factor that affects cell therapy outcomes, and transplantation of young hMSC appears to provide better functional recovery through anti-inflammatory effects, vessel maturation, and neurogenesis potentially by the dominance of trophic factor secretion.

SUBMITTER: Yamaguchi S

PROVIDER: S-EPMC6434451 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Age of donor of human mesenchymal stem cells affects structural and functional recovery after cell therapy following ischaemic stroke.

Yamaguchi Susumu S Horie Nobutaka N Satoh Katsuya K Ishikawa Takeshi T Mori Tsuyoshi T Maeda Hajime H Fukuda Yuhtaka Y Ishizaka Shunsuke S Hiu Takeshi T Morofuji Yoichi Y Izumo Tsuyoshi T Nishida Noriyuki N Matsuo Takayuki T

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 20170915 7

Cell transplantation therapy offers great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is unclear. We investigated the regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischaemic stroke. The quantities of human mesenchymal stem cell (hMSC) secreted brain-derived neurotrophic factor in vitro and of monocyte chemotactic protein-1 at day 7 in vivo were both significantly higher for young hMSC compared ...[more]

PMID: 28914133

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Project description:Although pontine strokes account for a small percentage of all ischaemic events, they can be associated with significant initial disability. These lesions may be missed on computed tomography and therefore magnetic resonance imaging is generally preferred for the assessment of brainstem strokes. The aetiopathogenesis of isolated pontine infarcts, not due to a significant compromise (occlusion or dissection) in the vertebrobasilar territory, still remains to be fully characterised. These strokes present with different symptoms, depending on the lesion location and size, partly reflecting the anatomical variability of the vertebrobasilar vessels. Progressive neurological deterioration is relatively common and has been associated with the extension of such lesions. However, many patients with significant infarcts in the pons will do well in the future and initial diffusion-weighted imaging may not add useful prognostication to the clinical assessment. We discuss here a case where an initially progressive presentation was associated with a marked improvement in both clinical and radiological assessments at 42 days.A 49-year-old white British man presented with left-sided weakness, incoordination, unsteadiness, cerebellar ataxic dysarthria and dysphonia. A baseline magnetic resonance imaging scan with diffusion-weighted imaging, T1-weighted and T2-weighted sequences showed an acute bilateral pontine infarct. On a repeat scan at 42 days, there was a 57.5% decrease in the size of the lesion on the high-resolution three-dimensional T1-weighted image and a corresponding improvement in the symptoms and the clinical assessments of this patient. The reduction in infarct size was also comparable to the decrease calculated between the baseline diffusion-weighted and the follow-up fluid attenuated inversion recovery sequences.This case report discusses the significant clinical improvement and corresponding lesion reduction in a patient that presented with worsening neurological symptoms and was diagnosed with acute bilateral ischaemic pontine infarction. Further studies, utilising structural and functional magnetic resonance imaging with follow-up scans, are needed to provide better insights into the underlying aetiopathology and recovery mechanisms of pontine stroke. These will help define the relationship between imaging parameters and outcome allowing for better prognosis along with the development of relevant rehabilitation programs for this group of patients.

Dataset Information

Age of donor of human mesenchymal stem cells affects structural and functional recovery after cell therapy following ischaemic stroke.

Publications

Age of donor of human mesenchymal stem cells affects structural and functional recovery after cell therapy following ischaemic stroke.

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