Mesenchymal Stromal Cell Characteristics and Regenerative Potential in Cardiovascular Disease: Implications for Cellular Therapy.

Administration of mesenchymal stromal cells (MSCs) is a promising strategy to treat cardiovascular disease (CVD). As progenitor cells may be negatively affected by both age and comorbidity, characterization of MSC function is important to guide decisions regarding use of allogeneic or autologous cells. Definitive answers on which factors affect MSC function can also aid in selecting which MSC donors would yield the most therapeutically efficacious MSCs. Here we provide a narrative review of MSC function in CVD based on a systematic search. A total of 41 studies examining CVD-related MSC (dys)function were identified. These data show that MSC characteristics and regenerative potential are often affected by CVD. However, studies presented conflicting results, and directed assessment of MSC parameters relevant to regenerative medicine applications was lacking in many studies. The predictive ability of in vitro assays for in vivo efficacy was rarely assessed. There was no correlation between quality of study reporting and study findings. Age mismatch was also not associated with study findings or effect size. Future research should focus on assays that assess regenerative potential in MSCs and parameters that relate to clinical success.

Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies.

Although the precise pathogenesis of schizophrenia is unknown, genetic, biomarker and imaging studies suggest involvement of the immune system. In this study, we performed a systematic review and meta-analysis of studies investigating factors related to the immune system in postmortem brains of schizophrenia patients and healthy controls. Forty-one studies were included, reporting on 783 patients and 762 controls. We divided these studies into those investigating histological alterations of cellular composition and those assessing molecular parameters; meta-analyses were performed on both categories. Our pooled estimate on cellular level showed a significant increase in the density of microglia (P=0.0028) in the brains of schizophrenia patients compared with controls, albeit with substantial heterogeneity between studies. Meta-regression on brain regions demonstrated this increase was most consistently observed in the temporal cortex. Densities of macroglia (astrocytes and oligodendrocytes) did not differ significantly between schizophrenia patients and healthy controls. The results of postmortem histology are paralleled on the molecular level, where we observed an overall increase in expression of proinflammatory genes on transcript and protein level (P=0.0052) in patients, while anti-inflammatory gene expression levels were not different between schizophrenia and controls. The results of this meta-analysis strengthen the hypothesis that components of the immune system are involved in the pathogenesis of schizophrenia.

Increased amount of bone marrow-derived smooth muscle-like cells and accelerated atherosclerosis in diabetic apoE-deficient mice.

AIMS: Atherosclerotic plaque development is accelerated in patients with diabetes. Bone marrow-derived smooth muscle-like cells have been detected in neointima and diabetes has a numerical and functional effect on circulating vascular progenitor cells. We hypothesized that an increased number of bone marrow-derived smooth muscle-like cells correlates with accelerated atherosclerosis in diabetic apoE-deficient mice. METHODS: ApoE(-/-) mice were subjected to total body irradiation and transplanted with bone marrow cells from GFP-transgenic mice. Mice were rendered diabetic by streptozotocin injection and examined after 4, 8, 11 and 15 weeks of diabetes. RESULTS: Diabetic mice showed a larger plaque area and a higher number of smooth muscle-like cells compared to non-diabetic mice at 11 and 15 weeks after diabetes induction. Bone marrow-derived smooth muscle-like cells were detected in atherosclerotic plaques of both diabetic and control mice, but numbers were higher in plaques of diabetic mice 11 weeks after induction of diabetes. The higher number of bone marrow-derived smooth muscle-like cells in plaque was associated with an increase in in vitro differentiation of smooth muscle-like cells from spleen mononuclear cells in diabetic mice. CONCLUSIONS: Diabetes increases the number of bone marrow-derived smooth muscle-like cells in atherosclerotic plaques and the differentiation of mononuclear cells towards smooth muscle-like cells, which may contribute to accelerated atherosclerotic plaque development in diabetic apoE(-/-) mice.