scholarly journals Hepatoprotective effect of bone marrow-derived mesenchymal stromal cells in CCl4-induced liver cirrhosis

3 Biotech ◽  
2021 ◽  
Vol 11 (2) ◽  
Author(s):  
Ashwini P. Aithal ◽  
Laxminarayana K. Bairy ◽  
Raviraja N. Seetharam ◽  
Naveen Kumar
Keyword(s):  
Bone Marrow ◽  
Liver Cirrhosis ◽  
Portal Vein ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Disease Model ◽  
Hepatoprotective Effect ◽  
Control Group ◽  
Multipotent Stem Cells ◽  
Tail Vein

AbstractBone marrow mesenchymal stromal cells (BM-MSCs) are multipotent stem cells which are ideal candidates for use in regenerative medicine. The objectives of this study were to evaluate the hepatoprotective effect of BM-MSC and its combination treatment with silymarin in carbon tetrachloride (CCl4)-induced liver cirrhosis animal model and to investigate whether tail vein or portal vein infusion was the ideal route for BM-MSC transplantation. 36 female Wistar rats were randomly divided into six groups (n = 6): Group 1 (normal control), Group 2 (received only CCl4, disease model), Group 3 (CCl4 + BM-MSCs through tail vein), Group 4 (CCl4 + BM-MSCs through portal vein), Group 5 (CCl4 + silymarin), Group 6 (CCl4 + BM-MSCs + silymarin). On the 21st day after treatment, blood samples were collected for biochemical estimations. After the experiment, the rats were sacrificed. Liver was dissected out and processed for histopathology and scanning electron microscopy studies. Liver enzyme and marker analysis, histopathological studies indicated that the combination of BM-MSCs and silymarin was effective in treating liver cirrhosis. Transplanted BM-MSCs in combination with silymarin ameliorated the liver tissue damage through their immunoregulatory activities. Among the two routes, the intravenous administration of cells through the tail vein was found to be more effective and safe.

scholarly journals Repeated Autologous Bone Marrow Transfusion through Portal Vein for Treating Decompensated Liver Cirrhosis after Splenectomy

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Weiwei Zhang ◽  
Mujian Teng ◽  
Baochi Liu ◽  
Qiling Liu ◽  
Xin Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Liver Cirrhosis ◽  
Liver Function ◽  
Portal Vein ◽  
Liver Stiffness ◽  
Autologous Bone Marrow ◽  
Control Group ◽  
Decompensated Liver Cirrhosis ◽  
Autologous Bone ◽  
The Impact

Objective. This study is aimed at examining the impact of repeated intraportal autologous bone marrow transfusion (ABMT) in patients with decompensated liver cirrhosis after splenectomy. Methods. A total of 25 patients with decompensated liver cirrhosis undergoing splenectomy were divided into ABMT and control groups. The portal vein was cannulated intraoperatively using Celsite Implantofix through the right gastroomental vein. Both groups were given a routine medical treatment. Then, 18 mL of autologous bone marrow was transfused through the port in the patients of the ABMT group 1 week, 1 month, and 3 months after laminectomy, while nothing was given to the control group. All patients were monitored for adverse events. Liver function tests, including serum albumin (ALB), alanine aminotransferase (ALT), total bilirubin (TB), prothrombin activity (PTA), cholinesterase (CHE), α-fetoprotein (AFP), and liver stiffness measurement (LSM), were conducted before surgery and 1, 3, and 6 months after surgery. Results. Significant improvements in ALB, ALT, and CHE levels and decreased LSM were observed in the ABMT group compared with those in the control group (P<0.05). TB and PTA improved in both groups but with no significant differences between the groups. No significant changes were observed in AFP in the control group, but it decreased in the ABMT group. No major adverse effects were noted during the follow-up period in the patients of either group. Conclusions. Repeated intraportal ABMT was clinically safe, and liver function of patients significantly improved. Therefore, this therapy has the potential to treat patients with decompensated liver cirrhosis after splenectomy. This trial was registered with the identification number of ChiCTR-ONC-17012592.

scholarly journals Molecular Imaging for Comparison of Different Growth Factors on Bone Marrow-Derived Mesenchymal Stromal Cells’ Survival and ProliferationIn Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Hongyu Qiao ◽  
Ran Zhang ◽  
Lina Gao ◽  
Yanjie Guo ◽  
Jinda Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Bioluminescence Imaging ◽  
Firefly Luciferase ◽  
Control Group ◽  
Induced Apoptosis

Introduction. Bone marrow-derived mesenchymal stromal cells (BMSCs) have emerged as promising cell candidates but with poor survival after transplantation. This study was designed to investigate the efficacy of VEGF, bFGF, and IGF-1 on BMSCs’ viability and proliferation bothin vivoandin vitrousing bioluminescence imaging (BLI).Methods. BMSCs were isolated fromβ-actin-Fluc+transgenic FVB mice, which constitutively express firefly luciferase. Apoptosis was induced by hypoxia preconditioning for up to 24 h followed by flow cytometry and TUNEL assay. 106BMSCs with/without growth factors were injected subcutaneously into wild type FVB mice’s backs. Survival of BMSCs was longitudinally monitored using bioluminescence imaging (BLI) for 5 weeks. Protein expression of Akt, p-Akt, PARP, and caspase-3 was detected by Western blot.Results. Hypoxia-induced apoptosis was significantly attenuated by bFGF and IGF-1 compared with VEGF and control groupin vitro(P<0.05). When combined with matrigel, IGF-1 showed the most beneficial effects in protecting BMSCs from apoptosisin vivo.The phosphorylation of Akt had a higher ratio in the cells from IGF-1 group.Conclusion. IGF-1 could protect BMSCs from hypoxia-induced apoptosis through activation of p-Akt/Akt pathway.

Chd1 Regulates Primitive State of Bone Marrow Mesenchymal Stromal Cells without Affecting Hematopoietic Support; An Insight on the Dissociation Between Primitive State and Niche Function

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1587-1587
Author(s):  
Il-Hoan Oh ◽  
Hyun-Kyung Choi
Keyword(s):  
Bone Marrow ◽  
Chromatin Remodeling ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Conflicts Of Interest ◽  
Expression Level ◽  
Control Group ◽  
Open Chromatin ◽  
Hematopoietic Stem ◽  
Primitive State

Abstract Mesenchymal stromal cells (MSCs) are characterized by heterogeneity in the proliferation/self-renewal potentials and hematopoietic supporting activity among subpopulations. Numerous studies have suggested that a primitive state of MSC subpopulation are correlated to its niche function to support hematopoietic stem cells (HSCs), but the mechanisms regulating primitive state of MSCs remains poorly understood. In the present study, we examined the role of a chromatin remodeling enzyme, chd1 in the maintenance of open chromatin and undifferentiated state of MSCs. We analyzed for expression in MSCs, the expression level of chd1 progressively decreased during in-vitro subculture (from 7 to 18 passages) in a manner proportional to the passage numbers. Moreover, chd1 expression was down regulated in the MSCs during their differentiation into adipogenic or osteogenic lineages, compared to proliferative state, indicating the correlations between MSC proliferation potentials and expression level of chd1. Next, we transduced human bone marrow-derived MSCs with shRNAs against chd1 and found that chd1 knock down MSCs (chd1-KD) exhibit significant loss of colony forming activity (CFU-F), decrease of cell proliferation and loss of multi-lineage differentiation towards osteogenic or adipogenic lineages. Moreover, chd1-KD MSCs exhibited lower level expression of pluripotency-related genes, oct-4, sox-2 and nanog, with concomitant increase of H3K9me3 on the promoters and decreased chromatin accessibility in the oct-4 promoter, suggesting that chd1 regulate open chromatin and multi-lineage potential of MSCs. However, KD of chd1 in MSCs did not affect the HSC-supporting activity of MSCs; human cord blood-derived CD34+ cells co-cultured on chd1-KD MSCs exhibited rather higher maintenance of primitive phenotype (CD34+90+) and higher repopulating activity in NOD/SCID-ɤC KO mice compared to those co-cultured on control group MSCs. Together, these results show that, while primitive state of MSCs are regulated by chromatin remodeling complex,chd1, the hematopoietic niche activity of MSCs is not directly influenced by the primitive state of MSCs, raising a questions on the prevailing notion that undifferentiated MSCs can better support hematopoietic function. Disclosures No relevant conflicts of interest to declare.

Mesenchymal Stromal Cells Accelerate Hematopoietic Reconstitution and Mediate An IL6-Dependent Regeneration of the Intestinal Epithelium of Lethally Irradiated Mice.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3846-3846
Author(s):  
Moira Francois ◽  
Elena Birman ◽  
Daniel L. Coutu ◽  
Kathy-Ann Forner ◽  
Jacques Galipeau
Keyword(s):  
Bone Marrow ◽  
Radiation Exposure ◽  
Mesenchymal Stromal Cells ◽  
Intestinal Epithelium ◽  
Stromal Cells ◽  
Conflicts Of Interest ◽  
Control Group ◽  
Hematopoietic Reconstitution ◽  
Radiation Induced ◽  
Epithelium Regeneration

Abstract Abstract 3846 Apoptosis of radiation-sensitive stem cells in the bone marrow and the gut are the main complications arising from radiation exposure, whether therapeutic or accidental. Bone marrow-derived mesenchymal stromal cells (MSC) were shown to exert regenerative properties through the secretion of factors which act in a paracrine manner. In this study, we demonstrated that a single intra-peritoneal injection of C57Bl/6 MSC rescued lethally irradiated Balb/c mice. Histological analysis and Ki67 immunostaining of jejunum sections collected 48 hours and 5 days post MSC injection indicated that MSC protected the gastro-intestinal epithelium from severe radiation-induced damages and prompted the regeneration of the gut by stimulating proliferation of the crypt stem cell pool. Using interleukin-6 null MSC, we demonstrated that IL-6 derived from the MSC played a role accelerating gastro-intestinal epithelium regeneration. We also observed that MSC injection prevented severe anemia and restored granulocyte and platelet counts to normal values faster than the control group. Accelerated regeneration of the bone marrow and extra-medullar hematopoiesis in the spleen of MSC transplanted mice corroborated this observation. Our results suggest that IL-6 derived from MSC or used on its own may be exploited to alleviate radiation induced injuries to patients undergoing radiotherapy or subject to accidental radiation exposure Disclosures: No relevant conflicts of interest to declare.

scholarly journals Analysis of Expansion Mesenchymal Stromal Cells in patients with low risk myelodysplastic syndrome

JBMTCT ◽  
2020 ◽  
Vol 1 (1) ◽  
pp. 8-14
Author(s):  
Fernando Barroso Duarte ◽  
Romélia Pinheiro Gonçalves Lemes ◽  
João Paulo Vasconcelos ◽  
Francisco Dário Rocha ◽  
Ilana Zalcberg ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
P53 Protein ◽  
P53 Gene ◽  
Low Risk ◽  
University Hospital ◽  
Control Group ◽  
Cross Sectional ◽  
Significance Level

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal hematopoiet­ic disorders characterized by ineffective hematopoiesis, cytopenias and dysplasia and one or more lineages. The stratification of MDS is made based on the percentage of bone marrow blasts, number of cytopenias and karyotype at diagnosis. Somatic mutations in the p53 tu­mor suppressor gene are found in approximately 50% of all human tumors, making it the most commonly mutated gene. The expression of p53 protein and the study of mutations is especially needed in the prognosis of MDS. In this context, the study aims to evaluate the expansion of mesenchymal stromal cells (MSCs) and the expression of p53 protein in pa­tients with SMD, low risk, according to the International Prognostic System (IPSS), in order to demonstrate the importance of these evaluations also diagnostics. This is a cross-sectional analytical study with review 3 adult patients of both sexes, the diagnosis of low-risk MDS receiving outpatient treatment at the University Hospital Walter Cantídio (HUWC). MSCs were characterized by immunophenotyping and screening of mutation of the p53 gene by Real Time PCR System (Applied Biosystems). For data analysis, the statistical software was used GraphPadPrism 5.0. Statistical differences between groups were checked by Student t or Mann-Whitney’s test significance level was p < 0.05 for all analyzes. The results showed a smaller expansion of MSCs in the bone marrow of patients with MDS compared with a control group. A survey of mutation of the p53 gene was negative in all patients. The results demonstrate an impairment in the growth of MSCs in patients with MDS, collaborating with the hypothesis that medullary microenvironment in MDS may be compromised contributing greater understanding of disease mechanisms. However studies with larger sample should be conducted in order to establish the best results.

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 Bone Marrow Mesenchymal Stromal Cells: Identification, Classification, and Differentiation

2022 ◽  
Vol 9 ◽  
Author(s):  
Qianmin Gao ◽  
Lipeng Wang ◽  
Sicheng Wang ◽  
Biaotong Huang ◽  
Yingying Jing ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Lineage Tracing ◽  
Multipotent Stem Cells ◽  
Pathological Conditions ◽  
Adipocyte Progenitors ◽  
Bone Marrow Mesenchymal Cells ◽  
Hematopoietic Niche

Bone marrow mesenchymal stromal cells (BMSCs), identified as pericytes comprising the hematopoietic niche, are a group of heterogeneous cells composed of multipotent stem cells, including osteochondral and adipocyte progenitors. Nevertheless, the identification and classification are still controversial, which limits their application. In recent years, by lineage tracing and single-cell sequencing, several new subgroups of BMSCs and their roles in normal physiological and pathological conditions have been clarified. Key regulators and mechanisms controlling the fate of BMSCs are being revealed. Cross-talk among subgroups of bone marrow mesenchymal cells has been demonstrated. In this review, we focus on recent advances in the identification and classification of BMSCs, which provides important implications for clinical applications.

Mechanisms of action and osteogenic activity of bone marrow mesenchymal stromal cells are donor dependent

2014 ◽  
Author(s):  
Julie Leotot ◽  
Angelique Lebouvier ◽  
Philippe Hernigou ◽  
Helene Rouard ◽  
Nathalie Chevallier
Keyword(s):  
Bone Marrow ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Mechanisms Of Action ◽  
Osteogenic Activity
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