scholarly journals Hypoxia-Preconditioned Wharton’s Jelly-Derived Mesenchymal Stem Cells Mitigate Stress-Induced Apoptosis and Ameliorate Human Islet Survival and Function in Direct Contact Coculture System

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Somayeh Keshtkar ◽  
Maryam Kaviani ◽  
Zahra Jabbarpour ◽  
Fatemeh Sabet Sarvestani ◽  
Mohammad Hossein Ghahremani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Islets ◽  
Wharton’S Jelly ◽  
Isolated Pancreatic Islets ◽  
Wharton's Jelly ◽  
Coculture System ◽  
Induced Apoptosis ◽  
And Function ◽  
Islet Survival

Protection of isolated pancreatic islets against hypoxic and oxidative damage-induced apoptosis is essential during a pretransplantation culture period. A beneficial approach to maintain viable and functional islets is the coculture period with mesenchymal stem cells (MSCs). Hypoxia preconditioning of MSCs (Hpc-MSCs) for a short time stimulates the expression and secretion of antiapoptotic, antioxidant, and prosurvival factors. The aim of the present study was to evaluate the survival and function of human islets cocultured with Hpc-MSCs. Wharton’s jelly-derived MSCs were subjected to hypoxia (5% O2: Hpc) or normoxia (20% O2: Nc) for 24 hours and then cocultured with isolated human islets in direct and indirect systems. Assays of viability and apoptosis, along with the production of reactive oxygen species (ROS), hypoxia-inducible factor 1-alpha (HIF-1α), apoptotic pathway markers, and vascular endothelial growth factor (VEGF) in the islets, were performed. Insulin and C-peptide secretions as islet function were also evaluated. Hpc-MSCs and Nc-MSCs significantly reduced the ROS production and HIF-1α protein aggregation, as well as downregulation of proapoptotic proteins and upregulation of antiapoptotic marker along with increment of VEGF secretion in the cocultured islet. However, the Hpc-MSCs groups were better than Nc-MSCs cocultured islets. Hpc-MSCs in both direct and indirect coculture systems improved the islet survival, while promotion of function was only significant in the direct cocultured cells. Hpc potentiated the cytoprotective and insulinotropic effects of MSCs on human islets through reducing stressful markers, inhibiting apoptosis pathway, enhancing prosurvival factors, and promoting insulin secretion, especially in direct coculture system, suggesting the effective strategy to ameliorate the islet quality for better transplantation outcomes.

scholarly journals CHIP Reverses Hyperglycemia-associated PTEN Stability in Wharton's Jelly Derived Mesenchymal Stem Cells and Promotes Its Therapeutic Potential Against Diabetes-induced Cardiac Injury

2021 ◽  
Author(s):  
Ayaz Ali ◽  
Wei-Wen Kuo ◽  
Chia-Hua Kuo ◽  
Jeng-Feng Lo ◽  
Ray-Jade Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Injury ◽  
Wharton’S Jelly ◽  
Therapeutic Effects ◽  
Downstream Signaling ◽  
Wharton's Jelly ◽  
Induced Apoptosis ◽  
And Oxidative Stress

Abstract BackgroundRecent studies indicate that umbilical cord stem cells are cytoprotective against several disorders. One critical limitation in using stem cells is reduction in their viability under stressful conditions, such as diabetes. However, the molecular intricacies responsible for diabetic conditions are not fully elucidated.MethodsEffects of HG on Wharton's jelly derived mesenchymal stem cells (WJMSCs) viability was evaluated by MTT assay and flow cytometry. The mechanism responsible for HG-induced PTEN degradation was assessed using loss and gain of function, immunofluorescence, co-immunoprecipitation, and western blot analysis. Co-culturing of CHIP-overexpressed WJMSCs with embryo derived cardiomyoblasts was performed to analyze their ameliorative effects. The therapeutic effects of CHIP expressing WJMSCs were further validated in Sprague Dawley male (eight weeks old) STZ-induced diabetic animals by echocardiography, immunohistochemistry, hematoxylin eosin, and masson’s trichrome and TUNEL staining. Multiple comparisons were accessed through one‐way ANOVA and p-Value of <0.05 was considered statistically significant. ResultsIn this study, we found that high glucose (HG) conditions induced loss of chaperone homeostasis, stabilized PTEN, triggered the downstream signaling cascade, and induced apoptosis and oxidative stress in Wharton's jelly derived mesenchymal stem cells (WJMSCs). Increased CHIP expression promoted PTEN degradation via the ubiquitin-proteasome system and shortened its half-life during HG stress. Docking studies confirmed the interaction of CHIP with PTEN and FOXO3a with the Bim promoter region. Further, it was found that the chaperone system is involved in CHIP-mediated PTEN proteasomal degradation. CHIP depletion stabilizes PTEN whereas PTEN inhibition showed an inverse effect. CHIP overactivation suppressed the binding of FOXO3a with bim. Co-culturing CHIP overexpressed WJMSCs suppressed HG-induced apoptosis and oxidative stress in cardiac cells. Finally, CHIP overexpression and PTEN inhibition minimized blood glucose levels, improved body and heart weight, and rescued hyperglycemia-induced cardiac injury in diabetic rats. ConclusionThe current study suggests that CHIP confers resistance to apoptosis and oxidative stress and modulates PTEN and the downstream signaling cascade by promoting PTEN proteasomal degradation, thereby potentially exerting therapeutic effects against diabetes-induced cardiomyopathies.

Identify the role of Human Wharton's Jelly Mesenchymal Stem Cells in repairing injured uterine of rat

2021 ◽  
Vol 47 (1) ◽  
pp. 320-328
Author(s):  
Hezhu Wang ◽  
Xiaoqing Yang ◽  
Xiaojing Chen ◽  
Huihui Xie ◽  
Junxia Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Wharton’S Jelly ◽  
Wharton's Jelly

scholarly journals Exosomes derived from human umbilical cord Wharton's jelly mesenchymal stem cells ameliorate experimental lymphedema

2021 ◽  
Vol 11 (7) ◽  
Author(s):  
Zhao Ting ◽  
Yan Zhi‐xin ◽  
Tan You‐wen ◽  
Yang Fu‐ji ◽  
Sun Hui ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Wharton’S Jelly ◽  
Human Umbilical Cord ◽  
Wharton's Jelly

scholarly journals Different Angiogenic Potentials of Mesenchymal Stem Cells Derived from Umbilical Artery, Umbilical Vein, and Wharton’s Jelly

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Lu Xu ◽  
Jianjun Zhou ◽  
Jingyu Liu ◽  
Yong Liu ◽  
Lei Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Vein ◽  
Wharton’S Jelly ◽  
Tube Length ◽  
Branch Points ◽  
Differentiation Potential ◽  
Wharton's Jelly ◽  
Allogeneic Cell Therapy ◽  
Perivascular Stem Cells

Human mesenchymal stem cells derived from the umbilical cord (UC) are a favorable source for allogeneic cell therapy. Here, we successfully isolated the stem cells derived from three different compartments of the human UC, including perivascular stem cells derived from umbilical arteries (UCA-PSCs), perivascular stem cells derived from umbilical vein (UCV-PSCs), and mesenchymal stem cells derived from Wharton’s jelly (WJ-MSCs). These cells had the similar phenotype and differentiation potential toward adipocytes, osteoblasts, and neuron-like cells. However, UCA-PSCs and UCV-PSCs had more CD146+ cells than WJ-MSCs (P<0.05). Tube formation assay in vitro showed the largest number of tube-like structures and branch points in UCA-PSCs among the three stem cells. Additionally, the total tube length in UCA-PSCs and UCV-PSCs was significantly longer than in WJ-MSCs (P<0.01). Microarray, qRT-PCR, and Western blot analysis showed that UCA-PSCs had the highest expression of the Notch ligand Jagged1 (JAG1), which is crucial for blood vessel maturation. Knockdown of Jagged1 significantly impaired the angiogenesis in UCA-PSCs. In summary, UCA-PSCs are promising cell populations for clinical use in ischemic diseases.

Sign in / Sign up

Export Citation Format

Share Document