scholarly journals Bcl-xL Genetic Modification Enhanced the Therapeutic Efficacy of Mesenchymal Stem Cell Transplantation in the Treatment of Heart Infarction

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Xiaodong Xue ◽  
Yu Liu ◽  
Jian Zhang ◽  
Tao Liu ◽  
Zhonglu Yang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Therapy ◽  
Functional Recovery ◽  
Genetic Modification ◽  
Cell Apoptosis ◽  
Therapeutic Efficacy ◽  
Heart Infarction ◽  
Cell Engraftment

Objectives.Low survival rate of mesenchymal stem cells (MSCs) severely limited the therapeutic efficacy of cell therapy in the treatment of myocardial infarction (MI). Bcl-xL genetic modification might enhance MSC survival after transplantation.Methods.Adult rat bone marrow MSCs were modified with human Bcl-xL gene (hBcl-xL-MSCs) or empty vector (vector-MSCs). MSC apoptosis and paracrine secretions were characterized using flow cytometry, TUNEL, and ELISAin vitro.In vivo, randomized adult rats with MI received myocardial injections of one of the three reagents: hBcl-xL-MSCs, vector-MSCs, or culture medium. Histochemistry, TUNEL, and echocardiography were carried out to evaluate cell engraftment, apoptosis, angiogenesis, scar formation, and cardiac functional recovery.Results.In vitro, cell apoptosis decreased 43%, and vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and plate-derived growth factor (PDGF) increased 1.5-, 0.7-, and 1.2-fold, respectively, in hBcl-xL-MSCs versus wild type and vector-MSCs.In vivo, cell apoptosis decreased 40% and 26% in hBcl-xL-MSC group versus medium and vector-MSC group, respectively. Similar results were observed in cell engraftment, angiogenesis, scar formation, and cardiac functional recovery.Conclusions.Genetic modification of MSCs with hBcl-xL gene could be an intriguing strategy to improve the therapeutic efficacy of cell therapy in the treatment of heart infarction.

The Effect of Relaxin Treatment on Skeletal Muscle Injuries

2005 ◽  
Vol 33 (12) ◽  
pp. 1816-1824 ◽  
Author(s):  
Shinichi Negishi ◽  
Yong Li ◽  
Arvydas Usas ◽  
Freddie H. Fu ◽  
Johnny Huard
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Functional Recovery ◽  
Muscle Regeneration ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
C2c12 Cells ◽  
Muscle Injuries

Background Injured skeletal muscle can repair itself via spontaneous regeneration; however, the overproduction of extracellular matrix and excessive collagen deposition lead to fibrosis. Neutralization of the effect of transforming growth factor-β1, a key fibrotic cytokine, on myogenic cell differentiation after muscle injury can prevent fibrosis, enhance muscle regeneration, and thereby improve the functional recovery of injured muscle. Hypothesis The hormone relaxin, a member of the family of insulin-like growth factors, can act as an antifibrosis agent and improve the healing of injured muscle. Study Design Controlled laboratory study. Methods In vitro: Myoblasts (C2C12 cells) and myofibroblasts (transforming growth factor-β1-transfected myoblasts) were incubated with relaxin, and cell growth and differentiation were examined. Myogenic and fibrotic protein expression was determined by Western blot analysis. In vivo: Relaxin was injected intramuscularly at different time points after laceration injury. Skeletal muscle healing was evaluated via histologic, immunohistochemical, and physiologic tests. Results Relaxin treatment resulted in a dose-dependent decrease in myofibroblast proliferation, down-regulated expression of the fibrotic protein α-smooth muscle actin, and promoted the proliferation and differentiation of myoblasts in vitro. Relaxin therapy enhanced muscle regeneration, reduced fibrosis, and improved injured muscle strength in vivo. Conclusion Administration of relaxin can significantly improve skeletal muscle healing. Clinical Relevance These findings may facilitate the development of techniques to eliminate fibrosis, enhance muscle regeneration, and improve functional recovery after muscle injuries.

scholarly journals Transplantation of Neuregulin1-Overexpressing Bone Marrow Mesenchymal Cells Accelerates Motor Functional Recovery by Facilitating Neurite Outgrowth and Reducing Cell Apoptosis in Rat after Spinal Cord Injury

2020 ◽  
Author(s):  
Geng Wu ◽  
Herui Liu ◽  
Mei Zhu ◽  
Yang Wu ◽  
Yunlong Bai ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Bone Marrow ◽  
Neurite Outgrowth ◽  
Pc12 Cells ◽  
Functional Recovery ◽  
Cell Apoptosis ◽  
Cord Injury ◽  
Neuronal Chromatolysis

Abstract Background: Bone marrow mesenchymal stem cells (BMSCs) transplantation offers an attractive strategy for treating multiply neurological diseases. Neuregulin1 (NRG1) plays fundamental roles in nervous system development and nerve repair. In this study, we aimed to investigate whether transplantation of NRG1-overexpressing BMSCs could alleviate spinal cord injury (SCI), and to explore the possible underling mechanisms. Methods: In vitro, NRG1-overexpressing BMSCs were constructed via plasmid transfection, and co-cultured with PC12 cells subjected to oxygen-glucose deprivation (OGD). Neurite outgrowth, cell viability and apoptosis of PC12 cells were evaluated. In vivo, BMSCs, empty-vector BMSCs and NRG1-overexpressing BMSCs were transplanted respectively into rats with SCI. Rat locomotor functions, neuronal chromatolysis, neurite outgrowth and cell apoptosis were assessed respectively. Results: The results showed that NRG1-overexpressing BMSCs in vitro significantly expedited neurite growth, elevated growth-associated protein 43 expression, enhanced cell viability and rescued ODG-induced apoptosis in PC12 cells. In vivo, transplantation of NRG1-overexpressing BMSCs notably accelerated rat motor functional recovery, attenuated neuronal chromatolysis, promoted neurite outgrowth and reduced cell apoptosis after SCI. Moreover, NRG1-overexpressing BMSCs were also able to regulate apoptosis-related proteins expression after SCI. Conclusions: These findings demonstrate that NRG1-overexpressing BMSCs can accelerate motor functional recovery by facilitating neurite outgrowth and reducing cell apoptosis after SCI, suggesting that NRG1-overexpressing BMSCs may be a promising candidate for the treatment of SCI.

scholarly journals Age of donor of human mesenchymal stem cells affects structural and functional recovery after cell therapy following ischaemic stroke

2017 ◽  
Vol 38 (7) ◽  
pp. 1199-1212 ◽  
Author(s):  
Susumu Yamaguchi ◽  
Nobutaka Horie ◽  
Katsuya Satoh ◽  
Takeshi Ishikawa ◽  
Tsuyoshi Mori ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Ischaemic Stroke ◽  
Functional Recovery ◽  
Human Mesenchymal Stem Cells ◽  
Critical Factor ◽  
Human Mesenchymal Stem Cell ◽  
Donor Age ◽  
Sprague Dawley

Cell transplantation therapy offers great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is unclear. We investigated the regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischaemic stroke. The quantities of human mesenchymal stem cell (hMSC) secreted brain-derived neurotrophic factor in vitro and of monocyte chemotactic protein-1 at day 7 in vivo were both significantly higher for young hMSC compared with old hMSC. Male Sprague-Dawley rats subjected to transient middle cerebral artery occlusion that received young hMSC (trans-arterially at 24 h after stroke) showed better behavioural recovery with prevention of brain atrophy compared with rats that received old hMSC. Histological analysis of the peri-infarct cortex showed that rats treated with young hMSC had significantly fewer microglia and more vessels covered with pericytes. Interestingly, migration of neural stem/progenitor cells expressing Musashi-1 positively correlated with astrocyte process alignment, which was more pronounced for young hMSC. Aging of hMSC may be a critical factor that affects cell therapy outcomes, and transplantation of young hMSC appears to provide better functional recovery through anti-inflammatory effects, vessel maturation, and neurogenesis potentially by the dominance of trophic factor secretion.

scholarly journals Grape Seed Procyanidins Inhibit the Growth of Breast Cancer MCF-7 Cells by Down-Regulating the EGFR/VEGF/MMP9 Pathway

2021 ◽  
Vol 16 (2) ◽  
pp. 1934578X2199169
Author(s):  
Fan-ting Kong ◽  
Chen-xi He ◽  
Fan-lei Kong ◽  
Su-fen Han ◽  
Xiang-shun Kong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor ◽  
Cell Apoptosis ◽  
Growth Factor Receptor ◽  
Grape Seed ◽  
Dependent Manner ◽  
Flow Cytometric Data ◽  
Mcf 7

Breast cancer is the most common invasive cancer in women and the second leading cause of cancer death in women. However, it is not clear about its effective treatments. As a potential anticancer agent, grape seed procyanidins (GSPs) have been shown to inhibit the proliferation of various cancer cells in vitro and in vivo. In this study, it was shown that GSPs significantly inhibit MCF-7 cell proliferation in a concentration/time-dependent manner. The flow cytometric data clearly demonstrated that GSPs cause cell cycle arrest in the G2/M phase, followed by cell apoptosis. Moreover, it also confirmed that growth inhibition mediated by treatment with GSPs is related to the induction of apoptosis due to p53 elevation, purportedly by inhibition of the epidermal growth factor receptor (EGFR)/vascular endothelial growth factor (VEGF)/matrix metalloproteinase 9 (MMP9) pathway. Taken together, these findings suggest that GSPs inhibit MCF-7 cells proliferation and induce cell apoptosis by suppressing EGFR/VEGF/MMP9 pathway.

scholarly journals Glioblastoma stem cell (GSC)-derived PD-L1-containing exosomes activates AMPK/ULK1 pathway mediated autophagy to increase temozolomide-resistance in glioblastoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yong Zheng ◽  
Liang Liu ◽  
Yan Wang ◽  
Shan Xiao ◽  
Rongkang Mai ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Therapeutic Efficacy ◽  
Low Dose ◽  
High Dose ◽  
Glioblastoma Stem Cell ◽  
Compound C ◽  
Programmed Death ◽  
Protein Expressions

AbstractTemozolomide (TMZ)-resistance hampers the therapeutic efficacy of this drug for glioblastoma (GBM) treatment in clinic, and emerging evidences suggested that exosomes from GBM-derived stem cells (GSCs) contributed to this process, but the detailed mechanisms are still largely unknown. In the present study, we reported that GSCs derived programmed death-ligand 1 (PD-L1) containing exosomes activated AMPK/ULK1 pathway mediated protective autophagy enhanced TMZ-resistance in GBM in vitro and in vivo. Specifically, we noticed that continuous low-dose TMZ stimulation promoted GSCs generation and PD-L1 containing exosomes (PD-L1-ex) secretion in GBM cells, and that PD-L1-ex inhibited cell apoptosis and promoted cell autophagy to increased TMZ-resistance in GBM cells, which were reversed by co-treating cells with the autophagy inhibitor 3-methyladenine (3-MA). Consistently, upregulation of PD-L1 also increased TMZ-resistance in TS-GBM cells, and silencing of PD-L1 sensitized TR-GBM cells to TMZ. In addition, PD-L1-ex activated AMPK/ULK1 pathway to induce autophagy in TMZ treated GBM cells, and the inhibitors for AMPK (compound C) and ULK1 (SBI-0206965) promoted cell apoptosis in GBM cells co-treated with PD-L1-ex and high-dose TMZ. Finally, we evidenced that PD-L1-ex promoted tumor growth and Ki67 protein expressions to increase TMZ-resistance in GBM in vivo. Collectively, we concluded that GSCs-derived PD-L1-ex activated AMPK1/ULK1 signaling cascade mediated autophagy to increase TMZ-resistance in GBM, and this study provided potential strategies to improve the therapeutic efficacy of TMZ in GBM.

Autologous transplantation of mesenchymal stem cells into the portal vein of the miniature pig; a preliminary experiment for NOTES approach

2019 ◽  
Vol 98 (9) ◽  
pp. 350-355
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Therapy ◽  
Portal Vein ◽  
Liver Parenchyma ◽  
Miniature Pig ◽  
Hepatic Diseases ◽  
Study Results

Introduction: There is evidence that mesenchymal stem cells (MSCs) could trans-differentiate into the liver cells in vitro and in vivo and thus may be used as an unfailing source for stem cell therapy of liver disease. Combination of MSCs (with or without their differentiation in vitro) and minimally invasive procedures as laparoscopy or Natural Orifice Transluminal Endoscopic Surgery (NOTES) represents a chance for many patients waiting for liver transplantation in vain. Methods: Over 30 millions of autologous MSCs at passage 3 were transplanted via the portal vein in an eight months old miniature pig. The deposition of transplanted cells in liver parenchyma was evaluated histologically and the trans-differential potential of CM-DiI labeled cells was assessed by expression of pig albumin using immunofluorescence. Results: Three weeks after transplantation we detected the labeled cells (solitary, small clusters) in all 10 samples (2 samples from each lobe) but no diffuse distribution in the samples. The localization of CM-DiI+ cells was predominantly observed around the portal triads. We also detected the localization of albumin signal in CM-DiI labeled cells. Conclusion: The study results showed that the autologous MSCs (without additional hepatic differentiation in vitro) transplantation through the portal vein led to successful infiltration of intact miniature pig liver parenchyma with detectable in vivo trans-differentiation. NOTES as well as other newly developed surgical approaches in combination with cell therapy seem to be very promising for the treatment of hepatic diseases in near future.

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