Fig 5 - uploaded by Soheir Mahmoud Mahfouz
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Photomicrographs of liver tissue from CCl4 rat group stained with Hematoxylin and Eosin (200×) (A, B) showing nodular appearance of the liver due to fibrous septation. (C) (200×) and (D) (1,000×) showing foci of hepatocyte dysplasia.
Source publication
Human umbilical cord blood (UCB) cells have many advantages as grafts for cell transplantation. Here, we transplant
UCB cells into injured liver fibrosis, investigated the hepatic potential of UCB cells both in vitro and in vivo. a CCl4
rat model with liver fibrosis was prepared. Human (UCB) CD34＋ stem cell was separated with MACS (magnetic cell
so...
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Citations
... The cell pellet was resuspended in 300 μL PBS-EDTA buffer and the isolated BM-MSCs were cultured in 25-mL culture flasks in minimal essential medium (MEM) supplemented with 15% fetal bovine serum (FBS) and incubated for 2 h at 37°C with 5% humidified CO 2 . Lastly, a culture of adherent MSCs was maintained in MEM augmented with 30% FBS, 0.5% penicillin and streptomycin at 37°C with 5% CO 2 and air [12]. Cultured MSCs were recognized by their morphology and fluorescence activated cell sorting (FACS) using the surface markers CD29 + and CD44 + , which are specific to MSCs. ...
Background/aims:
The most appropriate route for bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation in the management of liver fibrosis remains controversial. This study investigated the therapeutic efficacy of intravenous and intrasplenic BM-MSC transplantation on carbon tetrachloride (CCl4)-induced rat liver fibrosis.
Methods:
Fifty rats were divided into 5 groups (n = 10 rats per group): healthy control group, CCl4 group, CCl4/ recovery group, CCl4/BM-MSC intravenous group, and CCl4/BM-MSC intrasplenic group. BM-MSCs were isolated, labeled with green fluorescent protein (GFP), and injected into fibrotic rats either intravenously or intrasplenically. Gene expression of interleukins (IL-1β and IL-6), interferon (INF)-γ, hepatic growth factor, and the hepatocyte-specific marker cytokeratin 18 was estimated by quantitative real-time reverse transcription-polymerase chain reaction. Vascular endothelial growth factor and connective tissue growth factor was detected by western blot analysis and enzyme-linked immunosorbent assay, respectively. At 2 weeks after intravenous and intrasplenic BM-MSC injections, GFP-positive cells were detected in liver tissue.
Results:
Both routes achieved a similar enhancement of liver function, which was confirmed by histopathological examination. The intravenous route was more effective than the intrasplenic route in reducing gene expression levels of IL-1β, IL-6, and INF-γ. However, fibrotic changes were still observed in the recovery group.
Conclusion:
Intravenous BM-MSC injection was an efficient and appropriate route for BM-MSC transplantation for the management of liver fibrosis.
... Currently, orthotopic liver transplantation is a gold therapeutic standard for liver fibrosis as it is a life-prolonging treatment [2]. In recent years, mesenchymal stem cell (MSC)-based therapy for liver fibrosis has gained increased interest due to proliferative ability of MSCs in vitro, and abundance of MSC source origins, which include adipose tissue [3][4][5], bone marrow [6,7] , and umbilical cord blood [8,9]. Moreover, the paracrine effects and differentiation capacity of MSCs are beneficial [10]. ...
... Growth factors contained in PRP have been proven to elevate the healing and anti-inflammation processes [39]. PRP supplemented in culture medium was shown to accelerate the proliferation, mobility, and immune-modulating capability of hADSCs [2,4,8,27]. PRP has also been widely used as an alternative for FBS in various areas, such as cosmetics industry or osteoarthritis therapies [7,30]. ...
Background: Transplantation of adipose-derived stem cells (ADSCs) is a potential therapy for a variety of liver diseases. Previous studies have shown that ADSC-based therapy is promising for liver fibrosis treatment. Recently, many publications have suggested that pretreating ADSCs with growth factors before transplantation can elevate the effectiveness of the therapy. Therefore, we hypothesize that human ADSCs (hADSCs) pretreated with platelet-rich plasma (PRP) and hepatocyte growth factor (HGF), compared to ADSCs alone, would accelerate the treatment effects on liver fibrosis in mice. Methods: The hADSCs were cultured solely with conventional media, or with HGF (human recombinant; 20 ng/ml), or with HGF and PRP (from healthy human blood, 10%), concomitantly added to the medium for 7 days before transplantation. Eight-week-old male mice were treated with CCl4 (1 ml/kg) for 11 weeks to induce liver fibrosis. The mice were then subsequently divided into: 1) Placebo group (PBS injection); 2) ADSCs/HGF+PRP (5x105HGF and PRP pre-treated cells/mice); 3) ADSCs/HGF (5x105HGF pre-treated cells/mice) and 4) ADSCs (5x105non-pretreated cells/mice). Results: Seven days post-transplantation, the alanine transaminase (ALT) level in the placebo was notably elevated (143.10±14.96 IU/L), compared to ALT levels of ADSCs-, ADSCs/HGF+PR-, and ADSCs/HGF-transplanted mice, which showed an improvement (67.94±18.57 IU/L, 49.44±7.56 IU/L, and 57.93±5.75 IU/L, respectively). The procollagen-α1 and alpha-smooth muscle actin (α-SMA) mRNA levels were significantly down-regulated in the ADSCs-transplanted group compared to those of the placebo. Importantly, these levels were lower in ADSCs/HGF+PR (procollagen-α1: 75.64±45.89; α-SMA: 36.17±36.09) than those of ADSCs/HGF (procollagen-α1: 212.8±84.35; α-SMA: 52.41±7.93) and ADSCs only (procollagen-α1: 310.50 ± 55.36; α-SMA: 184.70±14.06). Stem cell transplantation also improved histological index, reducing inflammation and collagen/necrotic structure accumulation. However, there were no statistical differences between three ADSCs treatment groups after 14 days after transplantation. Conclusion: Pre-treatment with PRP and HGF for 7 days enhanced the efficacy of ADSCs in alleviating liver fibrosis in vivo.
... In recent years, many studies have been conducted using MSCs for the treatment of cirrhosis. The sources of MSCs are diverse, such as cord blood (Abdel Aziz et al., 2010;Choudhery et al., 2013), bone marrow (Abdel Aziz et al., 2007;Yuan et al., 2014;Zhao et al., 2005), and adipose tissue (Choudhery et al., 2013;Seki et al., 2013;Zhang et al., 2014). Although these studies have shown that MSCs are a promising therapeutic choice for liver fibrosis (Berardis et al., 2015), the origin of MSCs from different sources may be problematic, with the varying safety and effectiveness of the cells (Reinisch et al., 2015). ...
Background: The application of mesenchymal stem cell (MSC) therapy in liver fibrosis treatment has been increasingly investigated in recent years. MSCs obtained from a variety of sources (e.g. bone marrow, umbilical cord blood and adipose tissue) have been studied and have achieved remarkable results. In this study, we compared the effects of adipose-derived mesenchymal stem cells (AD-MSC) transplantation with bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation in a mouse model of liver fibrosis, induced by carbon tetrachloride (CCl4).
Methods: Eight-week old mice were treated with CCl4 for 11 weeks to induce liver fibrosis then 5x105 cells were transplanted into mice via the tail vein.
Results: After 21 days of transplantation, the results showed that the stem cell treated groups ameliorated better than the placebo group. MSC treated groups showed reduced AST and ALT levels, down-regulated expression of extracellular matrix (ECM) genes, and improved liver histopathology. Both sources of MSCs (bone marrow and adipose tissue) were effective in the mouse model of liver fibrosis.
Conclusion: Our results also indicated that AD-MSC transplantation in mice accelerated liver regeneration better than BM-MSC transplantation.
... Isolated MSCs were cultured on 25 ml culture flasks in minimal essential medium (MEM) supplemented with 15% fetal bovine serum (FBS) and incubated for 2 hours at 37°C and 5% CO 2 . Adherent MSCs were cultured in MEM supplemented with 30% FBS, 0.5% penicillin, streptomycin and at 37°C in 5% CO 2 in air [13]. Cultured MSCs were confirmed by morphology ( Figure 1) and Florescent Analysis Cell Sorting (FACS) by detection of CD29 + and CD44 + specific to MSCs ( Figure 2). ...
Background and objective:
Human umbilical cord blood (UCB) cells and bone marrow mesenchymal stem cells (BM-MSCs) have numerous advantages as grafts for cell transplantation. We hypothesized differing impacts of human UCB cells and rat BM-MSCs on reversal of hepatic injury and revival of liver function in carbon tetrachloride (CCl4)-induced liver fibrosis.
Methods:
Forty rats were divided into 4 groups; control group, CCl4 group, CCl4/CD34(+) group and CCl4/BM-MSCs group. Blood samples were driven from rats at 4, 8 and 12 weeks to measure serum concentration of albumin and alanine aminotransferase (ALT). Quantitative expression of collagen Iα, TGF-β, α-SMA, albumin, MMP-2, MMP-9 and TNF-α were assessed by polymerase chain reaction. Histopathological examination of the liver tissue was performed. GFP labeled cells were detected in groups injected with stem cells.
Results:
Regarding liver function, CD34(+) were more efficient than BM-MSCs in elevating albumin (P<0.05) and reducing ALT (P<0.05) concentrations. Concerning gene expression, CD34(+) were more effective than BM-MSCs in reducing gene expressions of collagen Iα (P<0.01), TGF-β1 (P<0.01) and α-SMA (P<0.01). Both CD34(+) and BM-MSCs have the same efficacy in reducing TNF-α (P<0.001 and P<0.01, respectively). Furthermore, CD34(+) were more valuable than BM-MSCs in increasing gene expression of albumin (P<0.05) and MMP-9 (P<0.01).
Conclusion:
Taken together; human UCB CD34(+) stem cells were more efficient in improvement of experimental liver injury than BM-MSCs. This study highlighted an important role of human UCB CD34(+) stem cells in liver fibrosis therapy.
... The results of the current study showed that administration of stem cells reduced gene expression of MMP-2 and MMP-9 with higher expression in CCl 4 /CD34 + group. This is consistent with the finding of Abdel Aziz et al., 2010, who's found enhanced MMP-2 gene expression in liver tissues in the group that received human CD34 + stem cells. Also, Li et al., 2013, observed that combined treatment liver fibrosis with taurine, epigallocatechin gallate and genistein resulted in marked increase in the expression of MMP-2 in the HSC cells. ...
Human umbilical cord blood (UCB) cells and rat bone marrow mesenchymal stem cells (BM-MSCs) have many advantages as grafts for cell transplantation. The aim of this study was to investigate the impact of UCB cells and BM-MSCs on reversal of hepatic injury and revival of hepatic function in a rat model of carbon tetrachloride (CCl 4)-induced liver fibrosis.
Potassium bromate (KBrO 3) is used in many countries in cosmetic and food industries. In this research, we study the possible renoprotective effect of curcumin (CUR) and bone marrow meschenymal stem cells (BM-MSCs) on the actions of KBrO 3 in female rats. Thirty two female rats were categorized into four group, the first work as control, the second was exposed to KBrO 3 (100 mg/kg/day for 28 days in drinking water), the third and fourth where exposed to KBrO 3 like group 2 and co-treated with either CUR (100mg/kg, ip) twice a week or BM-MSCs (2x10 6 , ip for each rat) once a week for 4 weeks, respectively. Kidney function and oxidative stress parameters were measured calorimetrically in plasma. Expression of caspase-3 in kidney by real time PCR was measured by the comparative Ct (2-ΔΔCt) method. Apoptosis in kidney was evaluated by TUNNEL assay. The results indicated that treatment with KBrO3 caused nephrotoxicity, as evident by the measured renal structural and functional indices and oxidative stress markers in plasma. CUR and BM-MSCs co-treatment significantly abated most of the indices and biomarkers of the renal toxicity caused by KBrO3, suggesting their beneficial effects with the priority of CUR due to their antioxidant effect.
Purpose
Praziquantel (PZQ) is the conventional antibilharzial agent. Nevertheless, no antibilharzial prophylactic agents or 100% curable therapy approved and no reported data about use of human CD34⁺ Umbilical Cord Blood Stem Cells (CD34⁺UCBSCs) or Wharton Jelly Mesenchymal Stem Cells (WJMSCs) in prevention and/or complete eradication of acute S.mansoni granulomas in liver. We aimed to study possible prophylactic vs therapeutic role of human CD34⁺UCBSCs and WJMSCs in acute hepatic bilharzial granulomas in pre vs post-infected mice.
Methods
Seventy mice were divided into 7 groups (10 mice each): Normal, S.mansoni-infected, post-infected PZQ-treated, CD34⁺UCBSCs pre and post-infected, WJMSCs pre and post-infected. Serological, parasitological, histopathological evaluation using OCT4 & TGFB immunohistochemistry and quantitative image analysis assessment of TGFB-stained fibrogenesis in liver granulomas performed.
Results
Histopathologically, surprisingly and significantly, the prophylactic pre-infection stem cells (CD34⁺UCBSCs and WJMSCs) & similarly the post-infection CD34⁺UCBSCs treatment revealed eradication/reversal of the entire granulomas and no fibrosis. Moreover, post-infection PZQ treatment showed fewer and significantly smaller granulomas than post-infection WJMSCs treatment. Nevertheless, post-infection WJMSCs exhibited non-significant less TGFB-stained fibrogenesis.
Conclusion
CD34⁺UCBSCs exerted the best prophylactic and therapeutic roles in prevention and complete cure of acute hepatic S.mansoni granulomas over WJMSCs and PZQ. In contrast, only pre-infection WJMSCs exhibited similar preventive (prophylactic) effect. On the contrary, post-infection WJMSCs were the worst (incompletely reversed granulomas). Post-infection Praziquantel was overall better therapeutically than WJMSCs in this regard. Accordingly, when it comes to WJMSCs application, WJMSCs are better used as a pre-infection prophylactic and preventive tool rather than a post-infection therapy. Further studies are needed.
Stem cell-based therapy has received attention as a possible alternative to organ transplantation. The aim of this study was to assess the safety and efficacy of autologous transplantation of bone marrow (BM)-derived stromal cells in post-HCV liver cirrhosis patients.
10 × 10(6) of isolated human bone marrow (HBM)-stromal cells in 10 mL normal saline were injected in the spleen of 20 patients with end-stage liver cirrhosis guided by the ultrasonography, and then patients were followed up on monthly basis for six months.
A statistically significant decrease was detected in the total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) (p-value<0.01), prothrombin time (PT), and international normalized ratio (INR) levels (p-value<0.05), while a statistically significant increase in the albumin and PC (p-value<0.05) after follow-up.
This study suggested the safety, feasibility, and efficacy of the intrasplenic injection of autologous BM stromal cells in improving liver function in Egyptian patients with cirrhosis.
