Limits...
Effects of Exendin-4 on bone marrow mesenchymal stem cell proliferation, migration and apoptosis in vitro.

Zhou H, Li D, Shi C, Xin T, Yang J, Zhou Y, Hu S, Tian F, Wang J, Chen Y - Sci Rep (2015)

Bottom Line: Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, exerts cell-protective effects on many types of cells.However, blockade of the PI3K/Akt pathway with inhibitors suppressed the above cytoprotective effects of Ex-4, suggesting that the PI3K/Akt pathway is partly responsible for Ex-4-mediated MSC growth, mobilization and survival.These findings provide an attractive method of maximizing the effectiveness of MSC-based therapies in clinical applications.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.

ABSTRACT
Mesenchymal stem cells (MSC) are regarded as an attractive source of therapeutic stem cells for myocardial infarction. However, their limited self-renewal capacity, low migration capacity and poor viability after transplantation hamper the clinical use of MSC; thus, a strategy to enhance the biological functions of MSC is required. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, exerts cell-protective effects on many types of cells. However, little information is available regarding the influence of Ex-4 on MSC. In our study, MSC were isolated from bone marrow and cultured in vitro. After treatment with Ex-4, MSC displayed a higher proliferative capacity, increased C-X-C motif receptor 4 (CXCR4) expression and an enhanced migration response. Moreover, in H2O2-induced apoptosis, Ex-4 preserved mitochondrial function through scavenging ROS and balancing the expression of anti- and pro-apoptotic proteins, leading to the inhibition of the mitochondria-dependent cell death pathways and increased cell survival. Moreover, higher phospho-Akt (p-Akt) expression was observed after Ex-4 intervention. However, blockade of the PI3K/Akt pathway with inhibitors suppressed the above cytoprotective effects of Ex-4, suggesting that the PI3K/Akt pathway is partly responsible for Ex-4-mediated MSC growth, mobilization and survival. These findings provide an attractive method of maximizing the effectiveness of MSC-based therapies in clinical applications.

No MeSH data available.


Related in: MedlinePlus

MSC characterization.(A) Flow cytometry results demonstrated that MSC were uniformly negative for CD31, CD34 and CD45 and positive for CD29, CD73, CD90 CD105 and CD166 expression. (B) Isolated MSC showed fibroblast-like shapes and exhibited multi-differentiation capacity. Bar, 25 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4528192&req=5

f1: MSC characterization.(A) Flow cytometry results demonstrated that MSC were uniformly negative for CD31, CD34 and CD45 and positive for CD29, CD73, CD90 CD105 and CD166 expression. (B) Isolated MSC showed fibroblast-like shapes and exhibited multi-differentiation capacity. Bar, 25 μm.

Mentions: The MSC cultured in medium demonstrated a spindle-like or fibroblast-like shape with directionality and regularity. MSC were characterized by surface marker expression via FACS analysis. The results presented in Fig. 1A indicate that the MSC expressed CD29, CD73, CD90, CD105, and CD166, but these cells did not express the endothelial marker CD31 or the hematopoietic lineage markers CD34 and CD45, which was in agreement with previous reports. A differentiation assay was used to evaluate the multi-differentiation capacity of MSC. After several days of induction toward the adipogenic lineage, considerable morphological changes with lipid vacuole accumulation were observed (Fig. 1B). Following 21 days of osteogenic differentiation, positive staining for Alizarin Red S confirmed the differentiation of MSC into osteocytes.


Effects of Exendin-4 on bone marrow mesenchymal stem cell proliferation, migration and apoptosis in vitro.

Zhou H, Li D, Shi C, Xin T, Yang J, Zhou Y, Hu S, Tian F, Wang J, Chen Y - Sci Rep (2015)

MSC characterization.(A) Flow cytometry results demonstrated that MSC were uniformly negative for CD31, CD34 and CD45 and positive for CD29, CD73, CD90 CD105 and CD166 expression. (B) Isolated MSC showed fibroblast-like shapes and exhibited multi-differentiation capacity. Bar, 25 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4528192&req=5

f1: MSC characterization.(A) Flow cytometry results demonstrated that MSC were uniformly negative for CD31, CD34 and CD45 and positive for CD29, CD73, CD90 CD105 and CD166 expression. (B) Isolated MSC showed fibroblast-like shapes and exhibited multi-differentiation capacity. Bar, 25 μm.
Mentions: The MSC cultured in medium demonstrated a spindle-like or fibroblast-like shape with directionality and regularity. MSC were characterized by surface marker expression via FACS analysis. The results presented in Fig. 1A indicate that the MSC expressed CD29, CD73, CD90, CD105, and CD166, but these cells did not express the endothelial marker CD31 or the hematopoietic lineage markers CD34 and CD45, which was in agreement with previous reports. A differentiation assay was used to evaluate the multi-differentiation capacity of MSC. After several days of induction toward the adipogenic lineage, considerable morphological changes with lipid vacuole accumulation were observed (Fig. 1B). Following 21 days of osteogenic differentiation, positive staining for Alizarin Red S confirmed the differentiation of MSC into osteocytes.

Bottom Line: Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, exerts cell-protective effects on many types of cells.However, blockade of the PI3K/Akt pathway with inhibitors suppressed the above cytoprotective effects of Ex-4, suggesting that the PI3K/Akt pathway is partly responsible for Ex-4-mediated MSC growth, mobilization and survival.These findings provide an attractive method of maximizing the effectiveness of MSC-based therapies in clinical applications.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiology, Chinese PLA General Hospital, Beijing, China.

ABSTRACT
Mesenchymal stem cells (MSC) are regarded as an attractive source of therapeutic stem cells for myocardial infarction. However, their limited self-renewal capacity, low migration capacity and poor viability after transplantation hamper the clinical use of MSC; thus, a strategy to enhance the biological functions of MSC is required. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, exerts cell-protective effects on many types of cells. However, little information is available regarding the influence of Ex-4 on MSC. In our study, MSC were isolated from bone marrow and cultured in vitro. After treatment with Ex-4, MSC displayed a higher proliferative capacity, increased C-X-C motif receptor 4 (CXCR4) expression and an enhanced migration response. Moreover, in H2O2-induced apoptosis, Ex-4 preserved mitochondrial function through scavenging ROS and balancing the expression of anti- and pro-apoptotic proteins, leading to the inhibition of the mitochondria-dependent cell death pathways and increased cell survival. Moreover, higher phospho-Akt (p-Akt) expression was observed after Ex-4 intervention. However, blockade of the PI3K/Akt pathway with inhibitors suppressed the above cytoprotective effects of Ex-4, suggesting that the PI3K/Akt pathway is partly responsible for Ex-4-mediated MSC growth, mobilization and survival. These findings provide an attractive method of maximizing the effectiveness of MSC-based therapies in clinical applications.

No MeSH data available.


Related in: MedlinePlus