ABSTRACT
Human umbilical cord Wharton's jelly derived mesenchymal stem cells (hUCMSCs), a source of cell therapy, have received a great deal of attention due to their homing or migrating ability in response to signals emanating from damaged sites. It has been found that IL-1ß possesses the ability to induce the expression of matrix metalloproteinase-3 (MMP-3) in bone marrow MSCs. MMP-3 is involved in cell migration in various types of cells, including glioblastoma, vascular smooth muscle, and adult neural progenitor cells. In this study, we proposed that IL-1ß influences hUCMSCs migration involving MMP-3. The expression level of MMP-3 in IL-1ß-induced hUCMSCs was verified using cDNA microarray analysis, quantitative real-time PCR, ELISA and Western blot. Wound-healing and trans-well assay were used to investigate the cell migration and invasion ability of IL-1ß-treated hUCMSCs. In addition, we pre-treated hUCMSCs with interleukin-1 receptor antagonist, MMP-3 inhibitors (ALX-260-165, UK 356618), or transfected with MMP-3 siRNA to confirm the role of MMP3 in IL-1ß-induced cell migration. Our results showed that IL-1ß induced MMP-3 expression is related to the migration of hUCMSCs. Moreover, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126, p38 inhibitor SB205380, JNK inhibitor SP600125 and Akt inhibitor GSK 690693 decreased IL-1ß-induced MMP-3 mRNA and protein expression. The migration and invasion ability analyses showed that these inhibitors attenuated the IL-1ß-induced migration and invasion ability of hUCMSCs. In conclusion, we have found that IL-1ß induces the expression of MMP-3 through ERK1/2, JNK, p38 MAPK and Akt signaling pathways to enhance the migration of hUCMSCs. These results provide further understanding of the mechanisms in IL-1ß-induced hUCMSCs migration to injury sites.
Subject(s)
Interleukin-1beta/pharmacology , MAP Kinase Signaling System/drug effects , Matrix Metalloproteinase 3/metabolism , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/metabolism , Blotting, Western , Cell Line , Cell Movement/drug effects , Flow Cytometry , Humans , Signal Transduction/drug effects , Wound Healing/drug effectsABSTRACT
Stem cell-based regenerative therapy has emerged as a promising treatment for myocardial infarction. The aim of this study is to develop stiffness-controlled collagen scaffolds to allow proliferation and differentiation of mesenchymal stem cell (MSCs) into cardiac progenitor cells. In this study transforming growth factor ß2 (TGF-ß2), was used to induce stem cell differentiation into cardiac lineage cells. Collagen scaffolds were cross-linked with cross-linkers, 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), and N-Hydroxysuccinimide (NHS). The results showed that collagen scaffolds cross-linked with 25/50 and 50/50 of EDC mM/NHS mM cross-linkers exhibited little difference in shape and size, the scaffold cross-linked with 50/50 of cross-linkers demonstrated better interconnectivity and higher Young's modulus (31.8 kPa) than the other (15.4 kPa). SEM observation showed that MSCs could grow inside the scaffolds and interact with collagen scaffolds. Furthermore, greater viability and cardiac lineage differentiation were achieved in MSCs cultured on stiffer scaffolds. The results suggest that three-dimensional type I collagen scaffolds with suitable cross-linking to adjust for stiffness can affect MSC fate and direct the differentiation of MSCs into cardiac progenitor cells with/without TGF-ß2. These stiffness-controlled collagen scaffolds hold great potential as carriers for delivering MSCs differentiated cardiac progenitor cells into infracted hearts. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2234-2242, 2016.
Subject(s)
Cell Differentiation , Collagen/chemistry , Mesenchymal Stem Cells/metabolism , Myoblasts, Cardiac/metabolism , Tissue Scaffolds/chemistry , Humans , Mesenchymal Stem Cells/cytology , Myoblasts, Cardiac/cytologyABSTRACT
Objective To observe the effect of intravenous nutrition on blood serum triglyceride (TG),humoral immunity and cellular immunity function in premature infants.Methods Sixty premature infants were randomly divided into 3 groups:amino acid group (group A),amino acid plus medium-long chain fatty group (group B) and amino acid plus long chain fatty group (group C).Amino acid and the fatty were used on them from 24 hours after their birth,started from 1.0 g/(kg?d),increased progressively 0.5 g/(kg?d) until 3.0 g/(kg?d),totally 7 days.TG and immunoglobulin IgA,IgM,IgG,complement C3,C4 and T-lymphocyte subsets CD3,CD4,CD4/CD8 and NK cell were checked in the first day before treatment and the ninth day after treatment.Results Compared with before treatment,TG of 3 groups were elevated(Pa0.05).Compared with group A and B,NK cell in group C were decreased obviously(Pa