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Brain morphological and connectivity changes on MRI after stem cell therapy in a rat stroke model.

ABSTRACT: In animal models of stroke, behavioral assessments could be complemented by a variety of neuroimaging studies to correlate them with recovery and better understand mechanisms of improvement after stem cell therapy. We evaluated morphological and connectivity changes after treatment with human mesenchymal stem cells (hMSCs) in a rat stroke model, through quantitative measurement of T2-weighted images and diffusion tensor imaging (DTI). Transient middle cerebral artery occlusion rats randomly received PBS (PBS-only), FBS cultured hMSCs (FBS-hMSCs), or stroke patients' serum cultured hMSCs (SS-hMSCs). Functional improvement was assessed using a modified neurological severity score (mNSS). Quantitative analyses of T2-weighted ischemic lesion and ventricular volume changes were performed. Brain microstructure/connectivity changes were evaluated in the ischemic recovery area by DTI-derived microstructural indices such as relative fractional anisotropy (rFA), relative axial diffusivity (rAD), and relative radial diffusivity (rRD), and relative fiber density (rFD) analyses. According to mNSS results, the SS-hMSCs group showed the most prominent functional improvement. Infarct lesion volume of the SS-hMSCs group was significantly decreased at 2 weeks when compared to the PBS-only groups, but there were no differences between the FBS-hMSCs and SS-hMSCs groups. Brain atrophy was significantly decreased in the SS-hMSCs group compared to the other groups. In DTI, rFA and rFD values were significantly higher and rRD value was significant lower in the SS-hMSCs group and these microstructure/connectivity changes were correlated with T2-weighted morphological changes. T2-weighted volume alterations (ischemic lesion and brain atrophy), and DTI microstructural indices and rFD changes, were well matched with the results of behavioral assessment. These quantitative MRI measurements could be potential outcome predictors of functional recovery after treatment with stem cells for stroke.

SUBMITTER: Son JP

PROVIDER: S-EPMC7886198 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Brain morphological and connectivity changes on MRI after stem cell therapy in a rat stroke model.

Son Jeong Pyo JP Sung Ji Hee JH Kim Dong Hee DH Cho Yeon Hee YH Kim Suk Jae SJ Chung Jong-Won JW Chang Won Hyuk WH Kim Yun-Hee YH Kim Eun Hee EH Moon Gyeong Joon GJ Bang Oh Young OY

PloS one 20210216 2

In animal models of stroke, behavioral assessments could be complemented by a variety of neuroimaging studies to correlate them with recovery and better understand mechanisms of improvement after stem cell therapy. We evaluated morphological and connectivity changes after treatment with human mesenchymal stem cells (hMSCs) in a rat stroke model, through quantitative measurement of T2-weighted images and diffusion tensor imaging (DTI). Transient middle cerebral artery occlusion rats randomly rece ...[more]

PMID: 33592008

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Project description:Human adipose-derived mesenchymal stem cells (hAMSCs) are capable of immunomodulation and regeneration after neural injury. For these reasons, hAMSCs have been investigated as a promising stem cell candidate for stroke treatment. However, noninvasive experiments studying the effects of grafted stem cells in the host brain have not yet been reported. Cerebrospinal fluid (CSF), which can be collected without sacrificing the subject, is involved in physiological control of the brain and reflects the pathophysiology of various neurological disorders of the central nervous system (CNS). Following stem cell transplantation in a stroke model, quantitative analysis of CSF proteome changes can potentially reveal the therapeutic effect of stem cells on the host CNS. We examined hAMSC-secreted proteins obtained from serum-free culture medium by liquid chromatography-tandem mass spectrometry (LC-MS/MS), which identified several extracellular matrix proteins, supporting the well-known active paracrine function of hAMSCs. Subsequently, we performed label-free quantitative proteomic analysis on CSF samples from rat stroke models intravenously injected with hAMSC (experimental) or phosphate buffered saline (control). In total, 524 proteins were identified; among them, 125 and 91 proteins were increased and decreased with hAMSC treatment, respectively. Furthermore, gene set enrichment analysis revealed three proteins, 14-3-3 theta, MAG, and neurocan, that showed significant increases in the hAMSC-treated model; these proteins are core members of neurotrophin signaling, nerve growth factor (NGF) signaling, and glycosaminoglycan metabolism, respectively. Subsequent histological and neurologic function experiments validated proliferative neurogenesis in the hAMSC-treated stroke model. We conclude that (i) intravenous injection of hAMSCs can induce neurologic recovery in a rat stroke model and (ii) CSF may reflect the therapeutic effect of hAMSCs. Additionally, proteins as 14-3-3 theta, MAG, and neurocan could be considered as potential CSF biomarkers of neuroregeneration. These CSF proteome profiling results would be utilized as valuable resource in further stroke studies.

Dataset Information

Brain morphological and connectivity changes on MRI after stem cell therapy in a rat stroke model.

Publications

Brain morphological and connectivity changes on MRI after stem cell therapy in a rat stroke model.

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