scholarly journals Effects of bone marrow-derived mesenchymal stem cells transplanted via the portal vein or tail vein on liver injury in rats with liver cirrhosis

2015 ◽  
Vol 9 (4) ◽  
pp. 1292-1298 ◽  
Author(s):  
YING-MING SONG ◽  
CHANG-HONG LIAN ◽  
CHENG-SONG WU ◽  
AI-FANG JI ◽  
JUAN-JUAN XIANG ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Liver Injury ◽  
Portal Vein ◽  
Tail Vein

scholarly journals ID: 1035 Transplantation of umbilical cord blood-derived mesenchymal stem cells to treat liver cirrhosis in mice: a comparison of tail and portal vein injection

2017 ◽  
Vol 4 (S) ◽  
pp. 111
Author(s):  
Trinh Van Le ◽  
Nam Hai Nguyen ◽  
Huy Quang Do ◽  
Nhung Hai Truong
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Portal Vein ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Umbilical Cord Blood ◽  
Tail Vein ◽  
Positive Effects ◽  
Liver Histopathology

Background: Up to date, there have been some studies indicating positive effects of stem cells on treating the liver cirrhosis. In this study, we compared the effectiveness of two methods in which mesenchymal stem cells harvested from umbilical cord blood (UCB-MSCs) were transfused either via portal or tail veins to the mouse models of liver cirrhosis.  Methods: Liver cirrhosis was induced by CCl4 (1 ml/kg) on male Swiss mice within 11 weeks, followed by administration of 106 UCB-MSCs via the portal or tail vein. After 21 days, blood samples were collected for measuring transaminase, bilirubin and albumin activities. The expression of fibrosis-associated genes, specifically procollagen – alpha 1 and integrin – beta1, were assessed using qRT-PCR. The histopathology was also evaluated using hematoxylin/eosin, Masson trichrome staining and immunohistochemistry with collagen type 1 and alpha-SMA antibody.  Results: UCB-MSCs transplantation significantly improved post-21 days of treatment in the liver fibrosis mice as compared with placebo group. Notably, UCB-MSCs transferred through portal veins revealed a more positive effect than via tail veins as indicated by the improvement in the biochemical indexes, fibrosis-related genes expression, and liver histopathology.  Conclusion: The UCB-MSCs therapy proved to be a promising method for treating the liver cirrhosis. The method of delivering stem cells through portal vein was more effective than through tail vein

scholarly journals Transplantation of umbilical cord blood-derived mesenchymal stem cells to treat liver cirrhosis in mice: a comparison of tail and portal vein injection

2017 ◽  
Vol 4 (2) ◽  
pp. 201
Author(s):  
Trinh Van Le ◽  
Nam Hai Nguyen ◽  
Huy Quang Do ◽  
Huy Minh Le ◽  
Nhung Hai Truong
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Portal Vein ◽  
Cord Blood ◽  
Peer Review ◽  
Umbilical Cord Blood ◽  
Tail Vein ◽  
Integrin Beta1 ◽  
Peer Reviewers

Introduction: To date, there have been many studies indicating the positive effects of stem cells on treating liver cirrhosis. In this study, we used umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) for treatment in a mouse model of liver cirrhosis. Specifically, we determined and compared the effectiveness of two methods of MSC injection (tail vein versus portal vein). Methods: Liver cirrhosis in male Swiss mice (of age approximately 11 weeks or under) was induced by administration of carbon tetrachloride (CCl4; 1 ml/kg). One million UCB-MSCs were then transplanted into cirrhotic mice via the portal vein or tail vein. After 21 days, blood samples were collected for measurement of transaminase, bilirubin and albumin. The expression of fibrosis-associated genes, specifically procollagen – alpha 1 and integrin – beta1, were assessed using quantitative RT-PCR. The histopathology of the specimens was also evaluated using hematoxylin/eosin, Masson trichrome staining, and immunohistochemistry using collagen type 1 and alpha-SMA antibodies. Results: After 21 days, cirrhotic mice treated with UCB-MSCs showed recovery of bilirubin index, increase of liver albumin synthesis, inhibition of fibrosis-related gene expression (e.g. procollagen – alpha 1 and integrin – beta1), and remodeling of liver histology. From comparison of the different routes of transplantation, UCB-portal route was significantly more effective than UCB-tail route at reducing aspartate transaminase (AST) activity and bilirubin index (P<0.05), and inhibiting procollagen – alpha 1 and integrin – beta1 expression (P<0.05). UCB-MSCs from both transfusion routes showed accelerated improvement of liver histopathology. Conclusion: Therapeutic strategies using UCB-MSCs have proven to be promising for the treatment of liver cirrhosis. Injection of UCB-MSC via portal vein was more effective than tail vein for cirrhosis treatment.   Peer Review Details Peer review method: Single-Blind (Peer-reviewers: 02) Peer-review policy Plagiarism software screening?: Yes Date of Original Submission: 17 August 2017 Date accepted: 30 August 2017 Peer reviewers approved by: Dr. Lili Hami Editor who approved publication: Dr. Phuc Van Pham  

Bone marrow-derived mesenchymal stem cells ameliorate liver injury in a rat model of sepsis by activating Nrf2 signaling

2018 ◽  
Vol 151 (3) ◽  
pp. 249-262 ◽  
Author(s):  
Sally A. Selim ◽  
Samia A. Abd El-Baset ◽  
Asmaa A. A. Kattaia ◽  
Eman M. Askar ◽  
Eman Abd Elkader
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Injury ◽  
Rat Model

Molecular and Cellular Functions Distinguish Superior Therapeutic Efficiency of Bone Marrow CD45 Cells Over Mesenchymal Stem Cells in Liver Cirrhosis

Stem Cells ◽  
2015 ◽  
Vol 34 (1) ◽  
pp. 135-147 ◽  
Author(s):  
Prakash Baligar ◽  
Snehasish Mukherjee ◽  
Veena Kochat ◽  
Archana Rastogi ◽  
Asok Mukhopadhyay
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Cellular Functions ◽  
Therapeutic Efficiency

scholarly journals Bone Marrow-Derived Mesenchymal Stem Cells Overexpressing Akt1 Protect Against ConA-Induced Liver Injury in Mice

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5805-5805
Author(s):  
Lukun Zhou ◽  
Shuang Liu ◽  
Chuanyi M. Lu ◽  
Jianfeng Yao ◽  
Yuyan Shen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Liver Injury ◽  
Lethal Dose ◽  
Mouse Bone Marrow ◽  
Hematopoietic Stem ◽  
Ifn Γ

Abstract Liver injury associated with veno-occlusive disease and graft-versus-host disease (GVHD) is a frequent and severe complication of hematopoietic stem cell transplantation, and remains an important cause of transplant-related mortality. Bone marrow derived mesenchymal stem cells (MSCs) have been evaluated for the prevention and treatment of refractory GVHD. However, poor cell viability has limited the therapeutic capacity of mesenchymal stromal cell therapy in vivo. In this study, we genetically engineered C57BL/6 mouse bone marrow MSCs using ex vivo retroviral transduction to overexpress Akt1, a serine threonine kinase and pro-survival signal protein, and tested the hypothesis that Akt1-expressing MSCs (Akt1-MSCs) are more resistant to apoptosis and can ameliorate acute liver injury induced by concanavalin A (ConA) in BALB/c mice. Cell proliferation and apoptosis analyses showed that, under both regular culture and high concentration IFN-γ (100 ng/mL) stimulation conditions, Akt1-GFP-MSCs had proliferation and survival (anti-apoptotic) advantages with down-regulated apoptosis pathways, compared to control GFP-MSCs. Twenty-four hours after receiving lethal dose of ConA (40 mg/kg, intravenous) (N=10 each group), no mouse survived, with or without 1x106 Akt1-MSCs or GFP-MSCs administration (intravenous); however, 3 and 1 survived in the 5×106 Akt1-MSCs group and 5×106 GFP-MSCs groups, respectively. In subsequent sub-lethal dose ConA (20 mg/kg) experiments, compared to GFP-MSCs, mice received Akt1-MSCs administration had significantly lower serum AST, ALT, TNF-α and IFN-γ levels and less histopathological abnormalities. In addition, Akt1-MSCs treated mice had significantly higher serum concentrations of IL-10, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). In vivo imaging showed that, hepatic fluorescence signal in sub-lethal ConA+Akt1-MSCs group was significantly stronger than ConA+GFP-MSCs group on day 0, and persisted up to 14 days, whereas the signal in ConA+GFP-MSCs, Akt1-MSCs and GFP-MSCs groups was negligible on both day 7 and day 14. Thus, bone marrow derived MSCs genetically enhanced with Akt1 had survival advantage in vitro and in vivo, and have the potential to be a potent therapy for prevention and amelioration of GVHD-associated liver impairment. Further translational pre-clinical studies are ongoing to further determine the efficacy, dosage and timing of administration of Akt1-MSCs in animal models. Disclosures No relevant conflicts of interest to declare.

scholarly journals Bone Marrow-Derived Mesenchymal Stem Cells Modified with Akt1 Ameliorates Acute Liver GVHD

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Lukun Zhou ◽  
Shuang Liu ◽  
Zhao Wang ◽  
Jianfeng Yao ◽  
Wenbin Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Injury ◽  
Therapeutic Effects ◽  
Hematopoietic Stem ◽  
Ifn Γ ◽  
Immunomodulatory Function

Abstract Background Liver injury associated with acute graft-versus-host disease (aGVHD) is a frequent and severe complication of hematopoietic stem cell transplantation and remains a major cause of transplant-related mortality. Bone marrow-derived mesenchymal stem cells (BM-MSCs) has been proposed as a potential therapeutic approach for aGVHD. However, the therapeutic effects are not always achieved. In this study, we genetically engineered C57BL/6 mouse BM-MSCs with AKT1 gene and tested whether AKT1-MSCs was superior to control MSCs (Null-MSCs) for cell therapy of liver aGVHD. Results In vitro apoptosis analyses showed that, under both routine culture condition and high concentration interferon-γ (IFN-γ) (100ng/mL) stimulation condition, AKT1-MSCs had a survival (anti-apoptotic) advantage compared to Null-MSCs. In vivo imaging showed that AKT1-MSCs had better homing capacity and longer persistence in injured liver compared to Null-MSCs. Most importantly, AKT1-MSCs demonstrated an enhanced immunomodulatory function by releasing more immunosuppressive cytokines, such as IL-10. Adoptive transfer of AKT1-MSCs mitigated the histopathological abnormalities of concanavalin A(ConA)-induced liver injury along with significantly lowered serum levels of ALT and AST. The attenuation of liver injury correlated with the decrease of TNF-α and IFN-γ both in liver tissue and in the serum. Conclusions In summary, BM-MSCs genetically modified with AKT1 has a survival advantage and an enhanced immunomodulatory function both in vitro and in vivo and thus demonstrates the therapeutic potential for prevention and amelioration of liver GVHD and other immunity-associated liver injuries.

Gene Modified Human Mesenchymal Stem Cells Expressing Osteoprotegerin Inhibit Osteoclast Activation and Increase Trabecular Bone Area in a Xenogeneic Murine Model of Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 505-505
Author(s):  
Neil Rabin ◽  
Chara Kyriakou ◽  
Reuben Benjamin ◽  
Arnold Pizzey ◽  
Orla Gallagher ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Trabecular Bone ◽  
Bone Disease ◽  
Lumbar Vertebrae ◽  
Bone Area ◽  
Tail Vein ◽  
Trabecular Bone Area

Abstract Bone disease in multiple myeloma (MM) results from increased osteoclast (OCL) numbers and activity, which is associated with an increase in RANK Ligand and reduction in osteoprotegerin (OPG). Systemic administration of recombinant OPG reduces MM bone disease, but the short half life of OPG limits its usefulness. Gene modified mesenchymal stem cells (MSCs) offer a potential means of delivering stable expression of OPG in vivo to reduce OCL activation and bone destruction. Bone marrow derived human MSCs were transduced with a self-inactivating bicistronic lentiviral vector containing human OPG and GFP (MSCOPG). Control vector was identical except the OPG was cloned in reverse orientation (MSCGPO). Efficient transduction was demonstrated by high GFP expression (96% MSCOPG, 92% (MSCGPO). Stable transgene expression of human OPG (hOPG) occurred for beyond 20 passages in vitro, and hOPG was detected in vivo after tail vein administration of MSCOPG (2ng/mL hOPG detected in mouse serum 1 week after tail vein administration of 3 x 106 MSCOPG). Immunophenotype and differentiation potential of MSCs were maintained following transduction. A xenogeneic model of MM was developed. 1 x 107 KMS-12-BM cells injected tail vein into b2 m NOD/SCID mice leads to tumour infiltration in the bone marrow at 6 weeks, with varied tumour take between the bones examined. Using histomorphometric analysis trabecular bone area (TBA) was assessed as the proportion of trabecular bone in 0.5625 mm2 of marrow space 0.2 mm from growth plate. OCL were recorded as the proportion lining the endocortical surface (%OcPm). Reduction of trabecular bone in the tibia is related to the amount of tumour (KMS-12-BM tibia with >70% tumour mean TBA 0.7+/− 0.2 vs. KMS-12-BM tibia with <70% tumour mean 5.1+/− 0.8, p<0.01, which is similar to non diseased animals). All subsequent analysis were carried out on tibia with >70% tumour. There was no change in trabecular bone in the lumbar vertebrae. OCL were increased in the tibia and lumbar vertebrae of tumour bearing mice (PBS group mean %OcPm 0.9+/− 0.3 and 1.1+/− 0.4 vs. KMS-12-BM group mean 7.2+/− 3.2 and 7.5 +/− 2.2 in tibia and lumbar vertebrae respectively, p=0.01 in both groups). We hypothesised that MSCs expressing OPG will prevent the increase in OCL and subsequent loss of trabecular bone. Infusion of unmanipulated MSC or MSCGPO had no effect on %OcPm or TBA in diseased animals. 1 x106 MSCOPG or MSCGPO were injected by tail vein 2, 3 and 4 weeks after KMS-12-BM injection. Another group received KMS-12-BM alone. All mice were culled at 6 weeks. Trabecular bone was increased in the tibia of tumour bearing mice treated with MSCOPG (mean TBA 1.4 +/− 0.5) compared to control animals receiving MSCGPO or tumour alone (mean TBA 0.6 +/− 0.2), p=0.03, with a trend showing a reduction of OCL in the tibia of the MSCOPG group (mean %OcPm 2.6+/− 1.0) vs. control group (mean %OcPm 4.2+/− 1.5, NS). Importantly in the lumbar vertebrae, OCL were reduced in the MSCOPG group (mean %OcPm 1.9 +/− 0.4) compared to control animals (mean %OcPm 3.5+/− 0.5), p<0.01. Conclusion: MSCs gene modified with OPG are able to increase TBA in the tibia and reverse OCL activation in a xenogeneic model of MM. Gene modified MSCs may have future potential in treating MM induced bone disease.

Resveratrol pretreatment enhanced homing of SDF-1α-preconditioned bone marrow-derived mesenchymal stem cells in a rat model of liver cirrhosis

2017 ◽  
Vol 119 (3) ◽  
pp. 2939-2950 ◽  
Author(s):  
Mehrdad Hajinejad ◽  
Parichehr Pasbakhsh ◽  
Ameneh Omidi ◽  
Keywan Mortezaee ◽  
Saied Nekoonam ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Liver Cirrhosis ◽  
Rat Model
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