scholarly journals The Role of Mesenchymal Stem Cells in Regulating PDGF and VEGF during Pancreatic Islet Cells Regeneration in Diabetic Animal Model

Folia Medica ◽  
2021 ◽  
Vol 63 (6) ◽  
pp. 875-883
Author(s):  
Agung Putra ◽  
Zakariya Hadi Suwiryo ◽  
Adi Muradi Muhar ◽  
Agus Widyatmoko ◽  
Fifin Luthfia Rahmi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Blood Glucose ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Pancreatic Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Prolonged Release ◽  
Pancreatic Islet Cells

Introduction: Diabetes is a heterogeneous group of metabolic diseases characterized by elevated blood glucose due to autoimmune disorder or a combination of insulin resistance and insulin deficiency. VEGF and PDGF are the main actors in the regeneration of damaged pancreatic tissue. However, the prolonged release of these molecules may induce fibrosis formation. Mesenchymal stem cells (MSCs) have a high potential to regenerate damaged pancreatic tissue by releasing PDGF and VEGF. Aim: This study aimed to investigate the effect of MSCs on the levels of PDGF and VEGF on days 2 and 44 in diabetic mice and determine the number of pancreatic islet cells and blood glucose levels. Materials and methods: This study used a post-control group design with animals divided into five groups: sham, control, and three treatment groups (P) which were given MSCs at doses of 1.5×105, 3×105, and 6×105 cells. The levels of PDGF, VEGF, and blood glucose were measured by enzyme-linked immunosorbent assay (ELISA), while the number of pancreatic islet cells was analyzed using H&E staining. Results: This study showed a significant increase of VEGF and PDGF levels on day 2 and a significant increase in islet cell percentages on day 44 in line with the decreased blood glucose level. However, there was no difference between VEGF and PDGF levels on day 44. Conclusions: MSCs regulate PDGF and VEGF levels in wound healing phases and remodel pancreatic islet β-cells regeneration to control blood glucose in diabetic model mice.

Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells (huMSCs) Carrying MicroRNA-342 Relieve Protect Severe Acute Pancreatitis Injury (SAP)

2021 ◽  
Vol 11 (9) ◽  
pp. 1838-1843
Author(s):  
Xiaohong Zhou ◽  
Xuzhong Hao ◽  
Feifei He
Keyword(s):  
Stem Cells ◽  
Acute Pancreatitis ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Severe Acute Pancreatitis ◽  
Pancreatic Tissue ◽  
Inflammatory Factors ◽  
Control Group ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord

To investigate whether exosomes (exo) derived from human umbilical cord mesenchymal stem cells (huMSCs) and microRNA (miRNA)-342 have a protective effect on severe acute pancreatitis (SAP). Human umbilical cord blood was collected to extract huMSC-exo. With sham-operated mice as control group (n = 10), the other mice were induced to SAP model (n = 20), while 10 of the SAP mice received treatment with huMSC-exo. ELISA was performed to determine amylase and TAP level as well as inflammatory factors and HE staining to evaluate pathological changes of pancreatic tissue. The expression of miR-342 and Shh, Ptchl, and Smo in the Hh signal pathway was detected using RT-qPCR. The expression of miR-342 and the mRNA expression of Shh, Ptchl, and Smo was higher than that in model group (p < 0.05). The level of serum amylase, trypsinogen, and IFN-γ,Fasl, and IL-6 was upregulated in pancreas tissues of SAP mice relative to healthy mice, but their levels were decreased upon treatment with huMSC-exo and slightly higher than those of the control group, just not significantly. Collectively, the huMSC-exo may activate the Hh signaling pathway by regulating the expression of miR-342 increasing the expression of Shh, Ptchl, and Smo, and thereby healing of damaged pancreatic tissues in SAP.

scholarly journals Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model

2021 ◽  
Vol 40 (1) ◽  
pp. 29
Author(s):  
Nur Anna C Sa’dyah ◽  
Agung Putra ◽  
Bayu Tirta Dirja ◽  
Nurul Hidayah ◽  
Salma Yasmine Azzahara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Significant Difference ◽  
T1 And T2

Introduction<br />Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase.<br /><br />Methods<br />In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. <br /><br />Results<br />The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p&lt;0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1.<br /><br />Conclusion<br />MSCs can suppress TGF levels in liver fibrosis induced rats.

scholarly journals Generation of pancreatic islet cells and progenitor cells from embryonic stem cells

Cell Research ◽  
2008 ◽  
Vol 18 (S1) ◽  
pp. S28-S28
Author(s):  
Wei Jiang ◽  
Song Chen ◽  
Yan Shi ◽  
Mingxiao Ding ◽  
Hongkui Deng
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Progenitor Cells ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Embryonic Stem ◽  
Pancreatic Islet Cells

scholarly journals Therapeutic Effects and Repair Mechanism of HGF Gene Transfected Mesenchymal Stem Cells on Injured Endometrium via Activating Phosphorylated c-Met

2021 ◽  
Author(s):  
Xuan Xu ◽  
Jianye Wang ◽  
Liu Dong ◽  
Qiong Xing ◽  
Ying Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Quantitative Polymerase Chain Reaction ◽  
Akt Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Therapeutic Effects ◽  
Related Factors ◽  
Paracrine Factors ◽  
Endometrial Epithelium

Abstract BackgroundThere are many studies on the advantages of mesenchymal stem cells (MSCs) that could secret various paracrine factors in repairing endometrial injury. It is necessary to improve the stability and effectiveness of MSCs. Hepatocyte growth factor (HGF), as one of the cytokines secreted by MSCs, plays a significant role in vascular repair and mesenchymal to epithelial transformation (MET). It can be deduced that HGF is closely related to the repair process of endometrium.Therefore, we aim to investigate the effect and mechanism of MSCs from umbilical cord transfected with HGF gene in the damaged mouse endometrium.MethodsHGF gene transfected MSCs were prepared by electroporation. After determining the cell characteristics and cell activity of HGF gene transfected MSCs, the ability of HGF gene transfected MSCs to express HGF was detected by enzyme-linked immunosorbent assay. Totally, 60 female mice were randomly divided into Control group, Saline group, MSCs group , and HGF gene-transfected MSCs (MSCshgf) group. Each group of mice received treatment after injury. HE staining were used to evaluate the changes in the thickness of endometrial epithelium and the number of endometrial glands. Immunofluorescence was used to evaluate the molecular repair effect. Real time fluorescent quantitative polymerase chain reaction was used to compare the expression of angiogenesis related factors. Western blot was used to detect the activation of HGF/c-Met and AKT signaling pathways.ResultsHGF gene transfected MSCs retained the characteristics of original MSCs, and the concentration of HGF secreted by MSCs transfected with HGF gene was higher than that of normal MSCs. Compared with normal MSCs, HGF gene transfected MSCs have a more effect in promoting the repair of damaged endometrial epithelium, mainly in significantly increasing the thickness of damaged endometrial epithelium, increasing the number of glands and proliferating cells(p<0.01). Meanwhile, HGF gene transfected MSCs can improve the expression level of endometrial vascular growth related factors and promote the MET process (p<0.01). At the same time, Western blotting confirmed that these repair effects were related to HGF activation of its receptor c-Met and downstream AKT signaling pathway.ConclusionsCompared with normal MSCs, HGF gene transfected MSCs have a more significant effect in repairing the damaged endometrial epithelium. This effect is achieved by activating the receptor c-Met of HGF and downstream AKT pathway.

scholarly journals Allogeneic diabetic mesenchymal stem cells transplantation in streptozotocin-induced diabetic rat

2008 ◽  
Vol 31 (6) ◽  
pp. 328 ◽  
Author(s):  
Qing-Yu Dong ◽  
Li Chen ◽  
Guan-Qi Gao ◽  
Lei Wang ◽  
Jun Song ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Body Weight ◽  
Blood Glucose ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Control Group ◽  
Pancreatic Regeneration ◽  
Insulin Producing Cells ◽  
The Status

Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stroma cells which can provide a potential therapy for diabetes mellitus. But the mechanism is still controversial. Also, the status of BM-MSCs under hyperglycemia is not known. In the present study, we investigated the status of BM-MSCs in experimental-diabetic rat and demonstrated the rescue of experimental diabetes by diabetic MSCs transplantation. Methods: BM-MSCs were cultured and the potential of multiple-differentiation was identified through induction into osteoblasts. MSCs of passage 3 were used for the following experiment. The MSCs were labeled with 5-bromo-2?-deoxyuridine (BrdU). Diabetes in rats was induced by STZ injection. The rats were divided into three groups: normal control group (no DM, rats treated with saline through tail vein, n=10); DM control group (DM, no transplantation of MSCs, n=20); experimental group (DM and transplantation of MSCs, n=20). Body weight and blood glucose of the rats were monitored during the experiment after transplantation of MSCs. Paraffin sections of pancreas were obtained from rats of each group. Immuno-histochemistry analysis and double immunofluorescence were used to detect the BM-MSCs in the pancreatic tissue and their differentiating state. Results: MSCs were 89.5% labeled by BrdU and DAPI, which was green/blue double stained under fluorescent microscopy. Transplantation of diabetic MSCs resulted in a reduction of hyperglycemia on day 45 in experimental diabetic rats compared with control rats (17.7 mM ±3.9 vs 27.8 mM ± 2.1, P < 0.05), There was also a difference between MSC-treated experimental diabetic rats and control rats in body weight (232.7 g ±19.7 vs 133.3g ±13.1, P < 0.05). Histological and morphometric analysis of the pancreas of experimental diabetic rats showed the presence and differentiation of transplanted MSCs into insulin-producing cells which evidenced by double-staining of anti-BrdU and insulin. Also, there were many small islets throughout the sections. Their mean area and diameter analysis revealed that they were smaller thancontrol islets (1835.7 ± 175.8 µm2 vs 13257.2 ± 1457.6 µm2; 43.5 ± 3.7 µm vs 119.9 ± 5.8 µm, respectively, P < 0.05). Conclusion: Allogeneic MSCs transplantation can reduce blood glucose level in recipient rats. A relatively small quantity of transplanted diabetic MSCs survive and transdifferentiate into insulin-producing cells in the pancreas of recipient rats. Upon transplantation these cells initiate endogenous pancreatic regeneration by neogenesis of islet of recipient origin. The present study demonstrates that diabetic MSCs retains its stemness and potential to induce pancreatic regeneration on transplantation.

scholarly journals Adult Human Biliary Tree Stem Cells Differentiate to β-Pancreatic Islet Cells by Treatment with a Recombinant Human Pdx1 Peptide

PLoS ONE ◽  
2015 ◽  
Vol 10 (8) ◽  
pp. e0134677 ◽  
Author(s):  
Vincenzo Cardinale ◽  
Rosa Puca ◽  
Guido Carpino ◽  
Gaia Scafetta ◽  
Anastasia Renzi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pancreatic Islet ◽  
Islet Cells ◽  
Biliary Tree ◽  
Pancreatic Islet Cells ◽  
Adult Human ◽  
Tree Stem
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