IntroductionMesenchymal stem cells (MSCs) are promising candidates for cell-based therapies. Human platelet lysate represents an efficient alternative to fetal bovine serum for clinical-scale expansion of MSCs. Different media used in culture processes should maintain the biological characteristics of MSCs during multiple passages. However, bone marrow-derived MSCs and adipose tissue-derived MSCs have not yet been directly compared with each other under human platelet lysate conditions. This study aims to conduct a direct head-to-head comparison of the biological characteristics of the two types of MSCs under human platelet lysate-supplemented culture conditions for their ability to be used in regenerative medicine applications.MethodsThe bone marrow- and adipose tissue-derived MSCs were cultured under human platelet lysate conditions and their biological characteristics evaluated for cell therapy (morphology, immunophenotype, colony-forming unit-fibroblast efficiency, proliferation capacity, potential for mesodermal differentiation, secreted proteins, and immunomodulatory effects).ResultsUnder human platelet lysate-supplemented culture conditions, bone marrow- and adipose tissue-derived MSCs exhibited similar fibroblast-like morphology and expression patterns of surface markers. Adipose tissue-derived MSCs had greater proliferative potential than bone marrow-derived MSCs, while no significantly difference in colony efficiency were observed between the two types of cells. However, bone marrow-derived MSCs possessed higher capacity toward osteogenic and chondrogenic differentiation compared with adipose tissue-derived MSCs, while similar adipogenic differentiation potential wase observed between the two types of cells. There were some differences between bone marrow- and adipose tissue-derived MSCs for several secreted proteins, such as cytokine (interferon-γ), growth factors (basic fibroblast growth factor, hepatocyte growth factor, and insulin-like growth factor-1), and chemokine (stem cell-derived factor-1). Adipose tissue-derived MSCs had more potent immunomodulatory effects than bone marrow-derived MSCs.ConclusionsAdipose tissue-derived MSCs have biological advantages in the proliferative capacity, secreted proteins (basic fibroblast growth factor, interferon-γ, and insulin-like growth factor-1), and immunomodulatory effects, but bone marrow-derived MSCs have advantages in osteogenic and chondrogenic differentiation potential and secreted proteins (stem cell-derived factor-1 and hepatocyte growth factor); these biological advantages should be considered systematically when choosing the MSC source for specific clinical application.

Microglia become activated during cerebral ischemia and exert pro-inflammatory or anti-inflammatory role dependent of microglial polarization. NADPH oxidase (NOX)-dependent reactive oxygen species (ROS) production in microglia plays an important role in neuronal damage after ischemic stroke. Recently, NOX and ROS are consistently reported to participate in the microglial activation and polarization; NOX2 inhibition or suppression of ROS production are shown to shift the microglial polarization from M1 toward M2 state after stroke. The voltage-gated proton channel, Hv1, is selectively expressed in microglia and is required for NOX-dependent ROS generation in the brain. However, the effect of Hv1 proton channel on microglial M1/M2 polarization state after cerebral ischemia remains unknown. In the present study, we investigated the role of microglial Hv1 proton channel in modulating microglial M1/M2 polarization during the pathogenesis of ischemic cerebral injury using a mouse model of photothrombosis. Following photothrombotic ischemic stroke, wild-type mice presented obvious brain infarct, neuronal damage and impaired motor coordination. However, mice lacking Hv1 (Hv1−/−) were partially protected from brain damage and motor deficits compared to wild-type mice. These rescued phenotypes in Hv1 −/−mice in ischemic stroke is accompanied by reduced ROS production, shifted the microglial polarization from M1 to M2 state. Hv1 deficiency was also found to shift the M1/M2 polarization in primary cultured microglia. Our study suggests that the microglial Hv1 proton channel is a unique target for modulation of microglial M1/M2 polarization in the pathogenesis of ischemic stroke.

The renal glomerular podocyte exhibits a highly arborized morphology. In comparison with the neuron, which is the best studied process-bearing cell, the podocyte major processes share many cell biological characteristics with neuronal dendrites. Both podocytes and neurons develop microtubule-based thick processes with branching morphology and both have thin actin-based projections (i.e. podocyte foot processes and dendritic spines). Formation of podocyte processes and neuronal dendrites depends on the assembly of microtubules. Because the assembly of microtubules is regulated by phosphorylation of microtubule-associated proteins, inhibition of protein phosphatases abolishes and inhibition of protein kinases promotes process formation. Podocytes and dendrites also share the machinery of intracellular traffic of membranous vesicles, as well as cytoskeletal elements, which is indispensable for the elongation of these processes. Furthermore, these two cell types share expression of various molecules working for signal transduction, transmembranous transport and intercellular contacts. Such common gene expression implies a similar transcriptional regulation in these cells. Concerning the formation of podocyte foot processes and dendritic branches, actin filaments are thought to play a central role in orchestrating the function of various molecules and the regulation of actin assembly is necessary to establish and maintain such sophisticated cellular architecture. The molecular mechanism of foot process formation seems to include Rho family small GTP-binding proteins, which are known to be responsible for the establishment of dendritic branching morphology.