scholarly journals Positively Correlated CD47 Activation and Autophagy in Umbilical Cord Blood-Derived Mesenchymal Stem Cells during Senescence

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Gee-Hye Kim ◽  
Yun Kyung Bae ◽  
Ji Hye Kwon ◽  
Miyeon Kim ◽  
Soo Jin Choi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cell Therapy ◽  
Critical Role ◽  
Therapeutic Effects ◽  
Stem Cell Maintenance ◽  
Selection Of

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro ( p < 0.01 ), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.

scholarly journals CD90- (Thy-1-) High Selection Enhances Reprogramming Capacity of Murine Adipose-Derived Mesenchymal Stem Cells

2013 ◽  
Vol 35 ◽  
pp. 573-579 ◽  
Author(s):  
Koichi Kawamoto ◽  
Masamitsu Konno ◽  
Hiroaki Nagano ◽  
Shimpei Nishikawa ◽  
Yoshito Tomimaru ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Tolerance Induction ◽  
Cell Types ◽  
Effective Strategy ◽  
Cell Sorter ◽  
High Selection ◽  
Selection Of

Background. Mesenchymal stem cells (MSCs), including adipose tissue-derived mesenchymal stem cells (ADSC), are multipotent and can differentiate into various cell types possessing unique immunomodulatory features. Several clinical trials have demonstrated the safety and possible efficacy of MSCs in organ transplantation. Thus, stem cell therapy is promising for tolerance induction. In this study, we assessed the reprogramming capacity of murine ADSCs and found that CD90 (Thy-1), originally discovered as a thymocyte antigen, could be a useful marker for cell therapy.Method. Murine ADSCs were isolated from B6 mice, sorted using a FACSAria cell sorter by selection ofCD90HiorCD90Lo, and then transduced with four standard factors (4F; Oct4, Sox2, Klf4, and c-Myc).Results. Unsorted,CD90Hi-sorted, andCD90Lo-sorted murine ADSCs were reprogrammed using standard 4F transduction.CD90HiADSCs showed increased numbers of alkaline phosphatase-positive colonies compared withCD90LoADSCs. The relative reprogramming efficiencies of unsorted,CD90Hi-sorted, andCD90Lo-sorted ADSCs were 100%, 116.5%, and 74.7%, respectively.CD90Hicells were more responsive to reprogramming.Conclusion.CD90HiADSCs had greater reprogramming capacity thanCD90LoADSCs, suggesting that ADSCs have heterogeneous subpopulations. Thus,CD90Hiselection presents an effective strategy to isolate a highly suppressive subpopulation for stem cell-based tolerance induction therapy.

scholarly journals Fetal liver mesenchymal stem cells restore ovarian function in premature ovarian insufficiency by targeting MT1

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Boxian Huang ◽  
Chunfeng Qian ◽  
Chenyue Ding ◽  
Qingxia Meng ◽  
Qinyan Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Ovarian Function ◽  
Ovarian Insufficiency ◽  
Apoptotic Genes

Abstract Background With the development of regenerative medicine and tissue engineering technology, almost all stem cell therapy is efficacious for the treatment of premature ovarian failure (POF) or premature ovarian insufficiency (POI) animal models, whereas little stem cell therapy has been practiced in clinical settings. The underlying molecular mechanism and safety of stem cell treatment in POI are not fully understood. In this study, we explored whether fetal mesenchymal stem cells (fMSCs) from the liver restore ovarian function and whether melatonin membrane receptor 1 (MT1) acts as a regulator for treating POI disease. Methods We designed an in vivo model (chemotherapy-induced ovary damage) and an in vitro model (human ovarian granulosa cells (hGCs)) to understand the efficacy and molecular cues of fMSC treatment of POI. Follicle development was observed by H&E staining. The concentration of sex hormones in serum (E2, AMH, and FSH) and the concentration of oxidative and antioxidative metabolites and the enzymes MDA, SOD, CAT, LDH, GR, and GPx were measured by ELISA. Flow cytometry (FACS) was employed to detect the percentages of ROS and proliferation rates. mRNA and protein expression of antiapoptotic genes (SURVIVIN and BCL2), apoptotic genes (CASPASE-3 and CASPASE-9), and MT1 and its downstream genes (JNK1, PCNA, AMPK) were tested by qPCR and western blotting. MT1 siRNA and related antagonists were used to assess the mechanism. Results fMSC treatment prevented cyclophosphamide (CTX)-induced follicle loss and recovered sex hormone levels. Additionally, fMSCs significantly decreased oxidative damage, increased oxidative protection, improved antiapoptotic effects, and inhibited apoptotic genes in vivo and in vitro. Furthermore, fMSCs also upregulated MT1, JNK1, PCNA, and AMPK at the mRNA and protein levels. With MT1 knockdown or antagonist treatment in normal hGCs, the protein expression of JNK1, PCNA, and AMPK and the percentage of proliferation were impaired. Conclusions fMSCs might play a crucial role in mediating follicular development in the POI mouse model and stimulating the activity of POI hGCs by targeting MT1.

scholarly journals Instant stem cell therapy: Characterization and concentration of human mesenchymal stem cells in vitro

2008 ◽  
Vol 16 ◽  
pp. 47-55 ◽  
Author(s):  
P Kasten ◽  
◽  
I Beyen ◽  
M Egermann ◽  
AJ Suda ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Human Mesenchymal Stem Cells

scholarly journals Enhanced therapeutic effects of umbilical cord mesenchymal stem cells after prolonged treatment for HBV- related liver failure and liver cirrhosis

2020 ◽  
Author(s):  
Yifan Jia ◽  
Xin Shu ◽  
Xiaoan Yang ◽  
Haixia sun ◽  
Huijuan Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Stem Cell ◽  
Cell Therapy ◽  
Liver Failure ◽  
Stem Cell Therapy ◽  
Prolonged Treatment ◽  
Therapeutic Effects ◽  
Failure Group

Abstract Background: This study aimed to investigate the therapeutic effect of umbilical cord mesenchymal stem cells (UCMSCs) on HBV-related liver failure and liver cirrhosis and to compare the different efficacies of UCMSCs after different treatment courses.Methods: This was an observational study that retrospectively considered a three-year period during which 513 patients who received stem cell infusion met the criteria of hepatic failure and liver cirrhosis were identified from databases of the Third Affiliated Hospital of Sun Yat-sen University. Eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the times of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and group D received less than 4 weeks. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and MELD scores were recorded and compared among different groups.Results: A total of 64 patients met the criteria of liver failure, and 59 patients met the criteria of liver cirrhosis. After UCMSC treatments, the levels of ALT, AST, and TBIL at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the PTA and MELD scores only gradually improved in the liver failure group. Four weeks after UCMSC treatment, patients with prolonged treatment with UCMSCs had higher TBIL decline levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there was no statistically significant difference in the levels of change for ALT, AST, TBIL, PTA value and the MELD score between patients with liver failure with prolonged treatment with UCMSCs and patients with liver cirrhosis with prolonged treatment with UCMSCs at all observation weeks. However, the median decline and cumulative decline in the TBIL level of patients with liver failure with a standard 4-week treatment course were higher than those of patients with liver cirrhosis with a standard 4-week treatment course.Conclusion: Peripheral infusion of UCMSCs showed good therapeutic effects for HBV-related liver failure and liver cirrhosis. Prolonging the treatment course can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.

scholarly journals Stem Cell Therapy for Spinal Cord Injury

2021 ◽  
Vol 30 ◽  
pp. 096368972198926
Author(s):  
Liyi Huang ◽  
Chenying Fu ◽  
Feng Xiong ◽  
Chengqi He ◽  
Quan Wei
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Combined Treatment ◽  
Therapeutic Effects ◽  
Cord Injury

Traumatic spinal cord injury (SCI) results in direct and indirect damage to neural tissues, which results in motor and sensory dysfunction, dystonia, and pathological reflex that ultimately lead to paraplegia or tetraplegia. A loss of cells, axon regeneration failure, and time-sensitive pathophysiology make tissue repair difficult. Despite various medical developments, there are currently no effective regenerative treatments. Stem cell therapy is a promising treatment for SCI due to its multiple targets and reactivity benefits. The present review focuses on SCI stem cell therapy, including bone marrow mesenchymal stem cells, umbilical mesenchymal stem cells, adipose-derived mesenchymal stem cells, neural stem cells, neural progenitor cells, embryonic stem cells, induced pluripotent stem cells, and extracellular vesicles. Each cell type targets certain features of SCI pathology and shows therapeutic effects via cell replacement, nutritional support, scaffolds, and immunomodulation mechanisms. However, many preclinical studies and a growing number of clinical trials found that single-cell treatments had only limited benefits for SCI. SCI damage is multifaceted, and there is a growing consensus that a combined treatment is needed.

scholarly journals Enhanced therapeutic effects of umbilical cord mesenchymal stem cells after prolonged treatment for HBV-related liver failure and liver cirrhosis

2020 ◽  
Author(s):  
Yifan Jia ◽  
Xin Shu ◽  
Xiaoan Yang ◽  
Haixia sun ◽  
Huijuan Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Stem Cell ◽  
Cell Therapy ◽  
Liver Failure ◽  
Stem Cell Therapy ◽  
Prolonged Treatment ◽  
Therapeutic Effects ◽  
Failure Group

Abstract Background: This study aimed to investigate the therapeutic effect of umbilical cord mesenchymal stem cells (UCMSCs) on HBV-related liver failure and liver cirrhosis and to compare the different efficacies of UCMSCs after different treatment courses. Methods: This was an observational study that retrospectively considered a three-year period during which 513 patients who received stem cell infusion met the criteria of hepatic failure and liver cirrhosis were identified from databases of the Third Affiliated Hospital of Sun Yat-sen University. Eligible patients were categorized into the liver failure group and liver cirrhosis group. The two groups were divided into different subgroups according to the times of stem cell therapy. In the liver failure group, group A received more than 4 weeks and group B received less than 4 weeks. In the liver cirrhosis group, patients who received more than 4 weeks of stem cell therapy belonged to group C, and group D received less than 4 weeks. The patients were followed up for 24 weeks. The demographics, clinical characteristics, biochemical factors, and MELD scores were recorded and compared among different groups. Results: A total of 64 patients met the criteria of liver failure, and 59 patients met the criteria of liver cirrhosis. After UCMSC treatments, the levels of ALT, AST, and TBIL at all postbaseline time points were significantly lower than those at baseline in the liver failure group and liver cirrhosis group; the PTA and MELD scores only gradually improved in the liver failure group. Four weeks after UCMSC treatment, patients with prolonged treatment with UCMSCs had higher TBIL decline levels than patients who terminated treatment with UCMSCs. After more than 4 weeks of UCMSC treatment, there was no statistically significant difference in the levels of change for ALT, AST, TBIL, PTA value and the MELD score between patients with liver failure with prolonged treatment with UCMSCs and patients with liver cirrhosis with prolonged treatment with UCMSCs at all observation weeks. However, the median decline and cumulative decline in the TBIL level of patients with liver failure with a standard 4-week treatment course were higher than those of patients with liver cirrhosis with a standard 4-week treatment course. Conclusion: Peripheral infusion of UCMSCs showed good therapeutic effects for HBV-related liver failure and liver cirrhosis. Prolonging the treatment course can increase the curative effect of UCMSCs for end-stage liver disease, especially for patients with cirrhosis.

scholarly journals Nitric oxide modulation in neuroinflammation and the role of mesenchymal stem cells

2021 ◽  
pp. 153537022199705
Author(s):  
Pan M Liy ◽  
Nur Nabilah A. Puzi ◽  
Shinsmon Jose ◽  
Sharmili Vidyadaran
Keyword(s):  
Nitric Oxide ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Neuronal Damage ◽  
Mesenchymal Stem Cell Therapy

Nitric oxide is a versatile mediator formed by enzymes called nitric oxide synthases. It has numerous homeostatic functions and important roles in inflammation. Within the inflamed brain, microglia and astrocytes produce large amounts of nitric oxide during inflammation. Excessive nitric oxide causes neuronal toxicity and death and mesenchymal stem cells can be used as an approach to limit the neuronal damage caused by neuroinflammation. Mesenchymal stem cell therapy ameliorates inflammation and neuronal damage in disease models of Alzheimer’s disease, Parkinson’s disease, and other neuroinflammatory disorders. Interestingly, we have reported that in vitro, mesenchymal stem cells themselves contribute to a rise in nitric oxide levels through microglial cues. This may be an undesirable effect and highlights a possible need to explore acellular approaches for mesenchymal stem cell therapy in the central nervous system.

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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