Combination therapy of human bone marrow–derived mesenchymal stem cells and minocycline improves neuronal function in a rat middle cerebral artery occlusion model

Abstract

BackgroundThe positive effects of human bone marrow–derived mesenchymal stem cells (hBM-MSCs) and minocycline on ischemic stroke models have been well described through numerous studies. The aim of this study was to evaluate the effectiveness of combination therapy of hBM-MSCs with minocycline in a middle cerebral artery occlusion rat model.MethodsForty male Sprague-Dawley rats were enrolled in this study. After right middle cerebral artery occlusion, rats were randomly assigned to one of four groups: control, minocycline, hBM-MSCs, or hBM-MSCs with minocycline. Rotarod test, adhesive-removal test, and modified neurological severity score grading were performed before and 1, 7, 14, 21, and 28 days after right middle cerebral artery occlusion. All rats were sacrificed at day 28. The volume of the infarcted area was measured with triphenyl tetrazolium chloride staining. Neuronal nuclear antigen (NeuN)- and vascular endothelial growth factor (VEGF)-positive cells in the ischemic boundary zone were assessed by immunofluorescence.ResultsNeurological outcome in the adhesive-removal test and rotarod test and modified neurological severity score were better in the combination therapy group than in the monotherapy and control groups. The volume of the infarcted area was smaller in the combination group compared with the others. The proportions of NeuN- and VEGF-positive cells in the ischemic boundary were highest in the combination therapy group.ConclusionsEarly combination therapy of hBM-MSCs with minocycline in an ischemic stroke model may enhance neurological recovery, reduce the volume of the infarcted area, and promote the expression of NeuN and VEGF in ischemic boundary cells.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1011-1) contains supplementary material, which is available to authorized users.

Combining Human Umbilical Cord Blood Cells With Erythropoietin Enhances Angiogenesis/Neurogenesis and Behavioral Recovery After Stroke

“…Because a study where brain-derived neurotrophic factor was administered alongside hBMSC in a stroke model showed positive results (42), variable approaches have been reported to enhance the neurorestorative effect of cell-based therapy (43). To present, reports have also revealed the therapeutic advantages of concomitant administration of other factors in cell-based therapy (44, 45). However, not all trials were successful.…”

Mesenchymal stem cells in chemotherapy‐induced peripheral neuropathy: A new challenging approach that requires further investigations

“…For example, the use of methylprednisolone provides a novel treatment protocol for enhancing therapeutic effects of BM‐MSCs in multiple sclerosis (Kim et al, ). Minocycline also improved neuronal function produced by BM‐MSCs in a rat middle cerebral artery occlusion model (Cho & Jeun, ). Administration of MSCs and ziprasidone enhanced the amelioration of ischemic brain damage in rats (Kaengkan et al, ).…”

Mitochondrial Transplantation Improves Stroke-Induced Brain Injury: Possible Involvement of Selective Component Recombination

“…Adult male Sprague-Dawley rats were used to induce tMCAO injury according to a previously described method with some modi cations [60,61]. In brief, after being anesthetized by an intraperitoneal injection of 2% pentobarbital sodium (45 mg/kg), the rats were placed in a prone position.…”

“…Neurobehavioral defects were evaluated 24 h after mitochondrial transplantation using multiple rating scales, including the Clark general functional de cit score [62,63], the Clark focal functional de cit score [62,63], the modi ed neurological severity score (mNSS) [61,64] and the Rotarod test [61,65] as previously described. Behavioral assessments were conducted by two skillful investigators who were both blinded to the animal groups.…”