Diabetes is a major global health issue and the number of individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) increases annually across multiple populations. Research to develop a cure must overcome multiple immune dysfunctions and the shortage of pancreatic islet β cells, but these challenges have proven intractable despite intensive research effort more than the past decades. Stem Cell Educator (SCE) therapy—which uses only autologous blood immune cells that are externally exposed to cord blood stem cells adhering to the SCE device, has previously been proven safe and effective in Chinese and Spanish subjects for the improvement of T1D, T2D, and other autoimmune diseases. Here, 4‐year follow‐up studies demonstrated the long‐term safety and clinical efficacy of SCE therapy for the treatment of T1D and T2D. Mechanistic studies found that the nature of platelets was modulated in diabetic subjects after receiving SCE therapy. Platelets and their released mitochondria display immune tolerance‐associated markers that can modulate the proliferation and function of immune cells. Notably, platelets also expressed embryonic stem cell‐ and pancreatic islet β‐cell‐associated markers that are encoded by mitochondrial DNA. Using freshly‐isolated human pancreatic islets, ex vivo studies established that platelet‐releasing mitochondria can migrate to pancreatic islets and be taken up by islet β cells, leading to the proliferation and enhancement of islet β‐cell functions. These findings reveal new mechanisms underlying SCE therapy and open up new avenues to improve the treatment of diabetes in clinics. Stem Cells Translational Medicine 2017;6:1684–1697

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The behavior of the binary mixed Langmuir monolayers of bovine insulin (INS) and phosphatidylcholine (PC) spread at the air-water interface was investigated under various subphase conditions. Pure and mixed monolayers were spread on water, on NaOH and phosphate-buffered solutions of pH 7.4, and on Zn(2+)-containing solutions. Miscibility and interactions between the components were studied on the basis of the analysis of the surface pressure (π)-mean molecular area (A) isotherms, surface compression modulus (C(s)(-1))-π curves, and plots of A versus mole fraction of INS (X(INS)). Our results indicate that intermolecular interactions between INS and PC depend on both the monolayer state and the structural characteristics of INS at the interface, which are strongly influenced by the subphase pH and salt content. Brewster angle microscopy (BAM) was applied to investigate the peptide aggregation pattern at the air-water interface in the presence of the studied lipid under any experimental condition investigated. The influence of the lipid on the INS behavior at the interface strongly depends on the subphase conditions.

In this paper, we aimed to continue the previous study undertaken with one segment of E1 protein belonging to the GB virus C/hepatitis G virus (GBV-C/HGV), specifically between the 53-66 amino acids and their palmitoyl derivative peptide. The sequence selection has been made on the basis of different prediction algorithms of hydrophobicity and antigenicity. Their interactions between two different in vitro membrane models, lipid Langmuir monolayers and vesicles of different lipidic composition, have been evaluated. For this purpose, different lipids, varying the charge and the unsaturations of the hydrocarbon chain 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) (DPPG) and 1,2-dioleoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (sodium salt) (DOPG), have been selected. Miscibility and peptides/lipids interactions have been analyzed on the basis of surface pressure (pi)-mean molecular area (A) isotherms, which have been recorded for pure and mixed monolayers of different composition spread at the air/water interface. Furthermore, E1(53-66) sequence and PalmE1(53-66) have been labeled with a fluorescent group, succinimidyl 6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoate (NBD succinimide), in order to study their behavior in the presence of vesicles. The obtained results are consistent with the existence of electrostatic (attractive) intermolecular interactions between the two positive net charges of the peptides and the polar heads of negative-charged lipids. However, both the lipidic membrane fluidity and the palmitic chain linked to the native peptide play an important role in the balance between the electrostatic forces established at the interface and the hydrophobic ones established inside the membrane. The fluorescence assays have demonstrated that electrostatic forces clearly predominate over the hydrophobic interactions only when the native sequence is retained at the polar interface of DPPG and DOPG vesicles. However, the palmitic tail linked to the peptide helped its penetration in the hydrophobic environment of the membrane, and this process was favored by decreasing the membrane fluidity.

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BackgroundSeveral recent studies have demonstrated the great potential of bone marrow cells in regenerative medicine, not only for their ability to differentiate to match a damaged cell type, but also because they synthesize and release various growth factors and cytokines.We examined the effect of bone marrow cell-conditioned medium in the healing process, especially in terms of fibroblast proliferation and migration.MethodsThese in vitro studies consisted of co-culture (without direct contact) of dermal fibroblasts with mononuclear bone marrow cells and the use of conditioned medium obtained from these cultures in a scratch wound model.ResultsMononuclear cells were found to increase the proliferation of fibroblasts, and the conditioned medium showed a stimulatory effect on the migration of fibroblasts.ConclusionWhen considered together with the observed increase in growth factor levels in conditioned medium, it appears that these cells act through a paracrine mechanism.

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