Background and Objectives: Bronchopulmonary dysplasia (BPD) has major effects in premature infants. Although previous literature has indicated that mesenchymal stem cells (MSCs) can alleviate lung pathology in BPD newborns and improve the survival rate, few research have been done investigating significantly differentially expressed genes in the lungs before and after MSCs therapy. The aim of this study is to identify differentially expressed genes in lung tissues before and after hAD-MSC treatment. Methods and Results: Human amnion-derived MSCs (hAD-MSCs) were cultured and met the MSCs criteria for cell phenotype and multidirectional differentiation. Then we confirmed the size of hAD-MSCs-EXOs and their expressed markers. An intratracheal drip of living cells showed the strongest effect on NHLI compared to cellular secretions or exosomes, both in terms of ameliorating pulmonary edema and reducing inflammatory cell infiltration. Through gene chip hybridization, PCR, and western blotting, acylaminoacyl-peptide hydrolase (APEH) expression was found to be significantly decreased under hyperoxia, and significantly increased after hAD-MSC treatment. Conclusions: The intratracheal transplantation of hAD-MSCs ameliorated NHLI in neonatal rats through APEH.
Mesenchymal stem cells (MSCs) can effectively regulate immune cell functions and therefore are promising for the treatment of autoimmune disorders, such as immune thrombocytopenia (ITP). Recent research has shown that three-dimensional (3D) culture method have many advantages over conventional culture with respect to MSC secretion and immunogenicity. In this study, 2D and 3D cultured MSCs were used to evaluate cytokine secretion, extracellular matrix (ECM) gene expression, immune regulatory activity, and therapeutic effects in a mouse model of ITP. MSCs cultured on scaffolds had higher expression levels of immune regulatory genes, such as IDO1, HLA-G, and PTGS2, and greater inhibitory activity against lymphocyte activation that those of 2D-MSCs. In addition, 3D-MSCs exhibited higher ECM expression and greater protection against interferon-γ (IFN-γ)-induced apoptosis. In a mouse study, ITP was induced by guinea pig anti-mouse platelet serum injections. Based on enzyme-linked immunosorbent assays, serum levels of the suppressive cytokine IL-10 were higher and IFN-γ levels were lower after intravenous injection with 3D-MSCs and with 2D-MSCs. Additionally, 3D-MSCs improved the body weight, spleen index, and platelet index relative to those for 2D-MSCs. Bone marrow homing was also significantly enhanced in the 3D group. Therefore, the 3D culture of MSCs is an effective technique for the treatment of ITP.
MiR-130b is overexpressed in children APL marrow tissues and associated with cell growth. MiR-130b may promote children APL progression by inducing cell proliferation and inhibiting apoptosis.
IntroductionDendritic cell (DCs) based cytotoxic T lymphocytes (CTLs) are commonly used in immunotherapy due to their specificity. The selection of appropriate cell origin and tumor antigen is the key point. The objective was to culture DCs and CTLs simultaneously from cord blood, and deliver antigen information using tumor derived exosomes.Material and methodsExosomes were collected from the human promyelocytic leukemia cell line HL-60 using ultracentrifugation. Prepared DCs from adherent cord blood mononuclear cells (MNCs) using SCF, GM-CSF, and IN-4. TNF-α and microRNA removed tumor-exosome were used to induce DCs maturation. DCs matured in the presence of HL-60 cell membrane protein extract or no antigen were set as control. CTLs was cultured from non-adherent MNCs by adding IFN-γ, IL-15, SCF, FLT-3L, anti-CD3, anti-CD28 and IL-2. The CTLs were analyzed by flow cytometry, cytotoxicity experiments and ELISA.ResultsDCs can be obtained from cord blood and express costimulatory molecules. After 15 days, the total number of the cells expanded 26.3 times, and more than 82% of the cells expressed CD3+CD8+ in the most amplified HL-60-Ex-DCs-CTL group. These CD3+CD8+ T cells generated by HL-60-Ex-DCs displayed specific cytotoxicity towards HL-60 and low lethality towards unrelated BALL-1 cells. ELISA results showed that the expressions of TNF-α and IFN-γ in HL-60-Ex-DCs or HL-60mPr-DCs activated CTLs were upregulated compared with the control group.ConclusionsCord blood CTLs generated by HL-60 derived exosome activated DCs displayed specific cytotoxicity towards HL-60 promyelocytic leukemia cells. Therefore cord blood and tumor derived exosomes provided a good source for adoptive immunotherapy.
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