Human Microglia Transplanted in Rat Focal Ischemia Brain Induce Neuroprotection and Behavioral Improvement

BACKGROUND AND PURPOSE: Microglia are resident immunocompetent and phagocytic cells of central nervous system (CNS), which produce various cytokines and growth factors in response to injury and thereby regulate disease pathology. The purpose of this study is to investigate the effects of microglial transplantation on focal cerebral ischemia model in rat. METHODS: Transient middle cerebral artery occlusion (MCAO) in rats was induced by the intraluminal filament technique. HMO6 cells, human microglial cell line, were transplanted intravenously at 48 hours after MCAO. Functional tests were performed and the infarct volume was measured at 7 and 14 days after MCAO. Migration and cell survival of transplanted microglial cells and host glial reaction in the brain were studied by immunohistochemistry. Gene expression of neurotrophic factors, cytokines and chemokines in transplanted cells and host rat glial cells was determined by laser capture microdissection (LCM) and quantitative real time-PCR. RESULTS: HMO6 human microglial cells transplantation group demonstrated significant functional recovery compared with control group. At 7 and 14 days after MCAO, infarct volume was significantly reduced in the HMO group. In the HMO6 group, number of apoptotic cells was time-dependently reduced in the infarct core and penumbra. In addition, number of host rat microglia/macrophages and reactive astrocytes was significantly decreased at 7 and 14 days after MCAO in the penumbra. Gene expression of various neurotrophic factors (GDNF, BDNF, VEGF and BMP7) and anti-inflammatory cytokines (IL4 and IL5) was up-regulated in transplanted HMO6 cells of brain tissue compared with those in culture. The expression of GDNF and VEGF in astrocytes in penumbra was significantly up-regulated in the HMO6 group. CONCLUSIONS: Our results indicate that transplantation of HMO6 human microglial cells reduces ischemic deficits and apoptotic events in stroke animals. The results were mediated by modulation of gliosis and neuroinflammation, and neuroprotection provided by neurotrophic factors of endogenous and transplanted cells-origin

Patient-Reported Outcomes of Kinematic vs Mechanical Alignment in Total Knee Arthroplasty: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Background: Total knee arthroplasty (TKA) is an effective treatment method for severe osteoarthritis of the knee. Poor alignment of a knee replacement has been associated with suboptimal clinical results. Traditionally, mechanical alignment (MA) has been considered the gold standard. In light of reports of decreased satisfaction with TKA, a new technique called kinematic alignment (KA) has been developed. The purpose of this study is to (1) review the results of KA and MA for TKA in randomized controlled trials based on the Western Ontario and McMaster Universities Arthritis Index score, the Oxford Knee Score, and the Knee Society Scores, (2) perform a meta-analyses of the randomized controlled trials with baseline and follow-up values of these parameters, and (3) discuss other shortcomings of this literature from the perspective of study design and execution. Methods: Two independent reviewers performed a systematic review of the English literature using the Embase, Scopus, and PubMed databases searching for randomized controlled trials of MA vs KA in TKA. Of the initial 481 published reports, 6 studies were included in the final review for meta-analysis. The individual studies were then analyzed to evaluate for risks of bias and inconsistencies of methodology. Results: A majority of studies demonstrated low risk of bias. All studies had fundamental technical issues by utilizing different techniques to achieve KA vs MA. There was no significant difference between KA and MA in these studies. Conclusions: There is no significant difference in any outcomes measured between KA and MA in TKA. Both statistical and methodological factors diminish the value of these conclusions