Bone Marrow Mesenchymal Stem Cells Exhibit a Transdifferentiation and Therapeutic Effects in a Murine Model of Orthotopic Hepatocellular Carcinoma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5133-5133
Author(s):  
Jun Ren ◽  
Hanfang Jiang ◽  
Lijun Di ◽  
Guohong Song
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Murine Model ◽  
Therapeutic Potential ◽  
Therapeutic Effects ◽  
Tumor Diameter ◽  
Hepatic Differentiation ◽  
Marrow Mesenchymal Stem Cells

Abstract Background and Aim: Bone marrow stem cells can differentiate into mature hepatocytes in vitro and in vivo. Moreover, recent study shown bone marrow mesenchymal stem cells (MSCs) are the most potent component in hepatic differentiation, suggesting that the transplantation of MSCs is a promising treatment for liver disease. However, little information is available about the therapeutic potential of MSCs transplantation in cases of hepatic cell carcinoma (HCC). Here, we transplanted bone marrow-derived MSCs to testify their effects in a murine model of orthotopic HCC. Methods:MSCs were obtained from tow male strains of β-galactosidase (β-gal) transgenic mouse(Rosa 26) and BALB/c mouse. MSCs were injected into tumor in BALB/c femal murine models of orthotopic HCC. Tumor growths were assessed by MRI on 7 days and survival rates were observed. When mouse was dying, the liver was removed from each treated mouse and evaluated by x-gal staining, and immunohistochemisty as well. Results: MSCs transplantation increased the survival of hepatocellular carcinoma-bearing mice(25.5±4.5days verus 21.3±1.7days, p=0.025) and decreased tumor diameter slightly (7.7±2.9mm versus 9.4±2.8mm, p=0.284). MSCs transplanted directly into the tumor and/ or normal hepatic parenchyma in the same liver lobe localized mainly at the border between the tumor cells and normal liver parenchyma, induced a large area of coagulative necrosis in the tumor bed. Some engrafted MSCs were positive for albumin. There are in the carcinoma bearing BALB/c mice with MSCs implanted, whether MSCs from BALB/c mice or from Rosa 26 transgenic mice. Conclusion: Our results suggest that the therapeutical effects of MSCs might be mediated not only by their differentiation into hepatocyte, but also mainly by they possess intrinsic antineoplastic properties.

scholarly journals Therapeutic effects of bone marrow mesenchymal stem cells‐derived exosomes on osteoarthritis

2021 ◽  
Vol 25 (19) ◽  
pp. 9281-9294
Author(s):  
Yi Jin ◽  
Min Xu ◽  
Hai Zhu ◽  
Chen Dong ◽  
Juan Ji ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Effects ◽  
Marrow Mesenchymal Stem Cells

scholarly journals Optimal H2O2 preconditioning to improve bone marrow mesenchymal stem cells’ engraftment in wound healing

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ling Guo ◽  
Juan Du ◽  
Dan-feng Yuan ◽  
Ya Zhang ◽  
Shu Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Therapeutic Potential ◽  
Optimal Protocol ◽  
Marrow Mesenchymal Stem Cells ◽  
Gsk 3Β ◽  
Migration Capacity

Abstract Background The transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising therapeutic strategy for wound healing. However, the poor migration capacity and low survival rate of transplanted BMSCs in wounds weaken their potential application. Objective To identify the optimal protocol for BMSCs preconditioned with H2O2 and improve the therapeutic efficacy using H2O2-preconditioned BMSCs in wound healing. Methods Mouse BMSCs were exposed to various concentrations of H2O2, and the key cellular functional properties were assessed to determine the optimal precondition with H2O2. The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds to evaluate their healing capacity and tissue engraftment. Results Treatment BMSCs with 50 μM H2O2 for 12 h could significantly enhance their proliferation, migration, and survival by maximizing the upregulation of cyclin D1, SDF-1, and its receptors CXCR4/7 expressions, and activating the PI3K/Akt/mTOR pathway, but inhibiting the expression of p16 and GSK-3β. Meanwhile, oxidative stress-induced BMSC apoptosis was also significantly attenuated by the same protocol pretreatment with a decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. Moreover, after the identification of the optimal protocol of H2O2 precondition in vitro, the migration and tissue engraftment of transfused BMSCs with H2O2 preconditioning were dramatically increased into the wound site as compared to the un-preconditioned BMSCs. The increased microvessel density and the speedy closure of the wounds were observed after the transfusion of H2O2-preconditioned BMSCs. Conclusions The findings suggested that 50 μM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSCs, which gives a considerable insight that this protocol may be served as a promising candidate for improving the therapeutic potential of BMSCs for wound healing.

scholarly journals Infusion of Bone Marrow Mesenchymal Stem Cells Attenuates Experimental Severe Acute Pancreatitis in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hang Zhao ◽  
Zhiying He ◽  
Dandan Huang ◽  
Jun Gao ◽  
Yanfang Gong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Pancreatitis ◽  
Mesenchymal Stem Cells ◽  
Survival Rate ◽  
Severe Acute Pancreatitis ◽  
Control Group ◽  
Therapeutic Effects ◽  
Isolation And Characterization ◽  
Marrow Mesenchymal Stem Cells

Background & Aims. Severe acute pancreatitis (SAP) remains a high-mortality disease. Bone marrow (BM) mesenchymal stem cells (MSCs) have been demonstrated to have plasticity of transdifferentiation and to have immunomodulatory functions. In the present study, we assessed the roles of MSCs in SAP and the therapeutic effects of MSC on SAP after transplantation.Methods. A pancreatitis rat model was induced by the injection of taurocholic acid (TCA) into the pancreatic duct. After isolation and characterization of MSC from BM, MSC transplantation was conducted 24 hrs after SAP induction by tail vein injection. The survival rate was observed and MSCs were traced after transplantation. The expression of TNF-αand IL-1βmRNA in the transplantation group was also analyzed.Results. The survival rate of the transplantation group was significantly higher compared to the control group (p<0.05). Infused MSCs were detected in the pancreas and BM 3 days after transplantation. The expression of TNF-αand IL-1βmRNA in the transplantation group was significantly lower than in the control group in both the pancreas and the lungs (p<0.05).Conclusions. MSC transplantation could improve the prognosis of SAP rats. Engrafted MSCs have the capacity of homing, migration, and planting during the treatment of SAP.

scholarly journals Promotion of Hepatic Differentiation of Bone Marrow Mesenchymal Stem Cells on Decellularized Cell-Deposited Extracellular Matrix

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Hongliang He ◽  
Xiaozhen Liu ◽  
Liang Peng ◽  
Zhiliang Gao ◽  
Yun Ye ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Extracellular Matrix ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Type I Collagen ◽  
Type Iii Collagen ◽  
Type I ◽  
Hepatic Differentiation ◽  
Marrow Mesenchymal Stem Cells

Interactions between stem cells and extracellular matrix (ECM) are requisite for inducing lineage-specific differentiation and maintaining biological functions of mesenchymal stem cells by providing a composite set of chemical and structural signals. Here we investigated if cell-deposited ECM mimickedin vivoliver's stem cell microenvironment and facilitated hepatogenic maturation. Decellularization process preserved the fibrillar microstructure and a mix of matrix proteins in cell-deposited ECM, such as type I collagen, type III collagen, fibronectin, and laminin that were identical to those found in native liver. Compared with the cells on tissue culture polystyrene (TCPS), bone marrow mesenchymal stem cells (BM-MSCs) cultured on cell-deposited ECM showed a spindle-like shape, a robust proliferative capacity, and a suppressed level of intracellular reactive oxygen species, accompanied with upregulation of two superoxide dismutases. Hepatocyte-like cells differentiated from BM-MSCs on ECM were determined with a more intensive staining of glycogen storage, an elevated level of urea biosynthesis, and higher expressions of hepatocyte-specific genes in contrast to those on TCPS. These results demonstrate that cell-deposited ECM can be an effective method to facilitate hepatic maturation of BM-MSCs and promote stem-cell-based liver regenerative medicine.

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