scholarly journals Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model

2021 ◽  
Vol 40 (1) ◽  
pp. 29
Author(s):  
Nur Anna C Sa’dyah ◽  
Agung Putra ◽  
Bayu Tirta Dirja ◽  
Nurul Hidayah ◽  
Salma Yasmine Azzahara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Significant Difference ◽  
T1 And T2

Introduction<br />Liver fibrosis (LF) results from the unregulated chronic wound healing process in liver tissue. Transforming growth factor-beta (TGF-β) is the major contributing cytokine of LF promotion through activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts (MFs) and increased extracellular matrix (ECM) deposition such as collagen leading to scar tissue development. Mesenchymal stem cells (MSCs) have an immunomodulatory capability that could be used as a new treatment for repairing and regenerating LF through suppression of TGF-β. This study aimed to examine the role of MSCs in liver fibrosis animal models through suppression of TGF-β levels without scar formation particularly in the proliferation phase.<br /><br />Methods<br />In this study, a completely randomized design was used with sample size of 24. Male Sprague Dawley rats were injected intraperitoneally (IP) with carbon tetrachloride (CCl4), twice weekly, for eight weeks to induce LF. Rats were randomly assigned to four groups: negative control, CCl4 group, and CCL4 + MSC-treated groups T1 and T2, at doses of 1 x 106 and 2x106 cells, respectively. TGF-β levels were analyzed by enzyme-linked immunosorbent assay (ELISA). One-way ANOVA and a least significant difference (LSD) was used to analyse the data. <br /><br />Results<br />The TGF levels of LF rat models decreased on day 7 after MSC administration. The levels of TGF-β in both MSC groups T1 and T2 decreased significantly compared with the control group (p&lt;0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1.<br /><br />Conclusion<br />MSCs can suppress TGF levels in liver fibrosis induced rats.

scholarly journals Application of pomegranate (Punica granatum Linn.) fruit extract for accelerating post-tooth extraction wound healing

2018 ◽  
Vol 51 (4) ◽  
pp. 189
Author(s):  
Intan Nirwana
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Treatment Group ◽  
Tooth Extraction ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Punica Granatum ◽  
Control Group ◽  
Wound Healing Process ◽  
Significant Difference

Background: Trauma occurring during tooth extraction can cause complications such as bleeding, infection, fracture and dry socket and constitutes an inflammatory response trigger. Pomegranate (Punica granatum Linn.) extract, which contains large amounts of punicallagin and ellagic acid, possesses various qualities, including; anti-inflammatory, anti-bacterial and anti-oxidant. Pomegranate extract can inhibit proinflammatory cytokine production, while also suppressing inflammation response thereby accelerating wound healing. Purpose: This study aimed to analyze the effect of pomegranate extract application to the tooth extraction wounds of Cavia cobaya (C. cobaya) on the expression of fibroblast growth factor-2 (FGF-2) and transforming growth factor β (TGF-β) on the fourth day of the wound-healing process. Methods: This study used 12 C. cobaya, divided into two groups, namely; control and treatment. The subjects were anesthetized, before their lower left central incisor was extracted and the entire socket filled with CMC-Na 3% in members of the control group and pomegranate extract in those of the treatment group. The twelve C. cobaya were sacrificed on day 4, their lower jaw subsequently being removed and decalcified for approximately 30 days. The mandibula tissue was stained using a immunohistochemical technique. FGF-2 and TGF-β were used to evaluate the healing process in the extracted tooth socket. Differences in the expression of FGF-2 and TGF-β were evaluated statistically by means of a t-test. Results: This study indicated a significant difference between the control and the treatment groups (p<0.05). The treatment group members whose sockets were filled with pomegranate extract showed high FGF-2 and TGF-β expression. Conclusion: This study confirmed that the administration of pomegranate extract to post-extraction tooth wounds of C. cobaya increases the expression of FGF-2 and TGF-β on day 4, thereby accelerating the wound healing process.

scholarly journals Mesenchymal Stem Cells Suppress Tgf-β Release to Decrease Α- Sma Expression in Ameliorating Ccl4-Induced Liver Fibrosis

2020 ◽  
Author(s):  
Agung Putra ◽  
Ken Wirastuti ◽  
Nur Anna Chalimah Sadyah ◽  
Setyo Trisnadi ◽  
Adi Muradi Muhar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Enzyme Linked Immunosorbent Assay ◽  
Sham Control ◽  
Immunohistochemistry Staining ◽  
Male Wistar Rats

Abstract Background: Liver fibrosis (LF) is the excessive deposition of extracellular matrix (ECM),produced by overactivated hepatic stellate cells, following prolonged transforming growth factor-β (TGF-b) stimulation.The ability of mesenchymal stem cells (MSCs) to improveLF has been reported. However, the mechanismsof MSCs to ameliorate LF through suppressing TGF-β and α-smooth muscle actin (a-SMA) remain unclear.In this study, we investigated the ability of MSCs to ameliorate LF by suppressing TGF-band a-SMA expression.Methods: Twenty-four,male, Wistar rats were injected intraperitoneal (IP) by with carbon tetrachloride (CCL4),twice weekly, for eight weeks, to induce LF. Rats were randomly assigned to four groups: Sham, Control, and MSC-treated groups, at doses of 1´106 (T1) and 2´106 (T2) cells. TGF-blevels were analyzed by enzyme-linked immunosorbent assay (ELISA),whereas a-SMA expression was determined by immunohistochemistry staining.Results: This study showed that TGF-bconcentrations significantly decreased in all treatment groupsat day 3 and 14. The T2 group showed lower TGF-blevels than that in the T1 group. This finding was in line with the observed decreasesina-SMA expression andnumber of colagen.Conclusions: MSCs treatmentamelioratedLF by suppressing TGF-b production,leading to decreaseda-SMA expressionin a CCL4-induced LF animal model.

scholarly journals Three-dimensional Differentiated Human Mesenchymal Stem Cells Exhibit Robust Antifibrotic Potential and Ameliorates Mouse Liver Fibrosis

2021 ◽  
Vol 30 ◽  
pp. 096368972098752
Author(s):  
Ja Sung Choi ◽  
Young-Jin Park ◽  
Sung-Whan Kim
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Liver Fibrosis ◽  
Culture System ◽  
Three Dimensional ◽  
3D Culture ◽  
Enzyme Linked Immunosorbent Assay ◽  
Therapeutic Mechanism ◽  
3D Culture System

Recently, three-dimensional (3D)-cultured adipose mesenchymal stem cells (ASCs) have provided an effective therapy for liver fibrosis. This study aimed to enhance the potential of human ASCs for antifibrosis or hepatocyte regeneration using a 3D culture system and investigate their therapeutic mechanism in experimental liver fibrosis. ASC-3Dc were generated in a 3D culture system and stimulated with four growth factors, namely epidermal growth factor, insulin-like growth factor (IGF)-1, fibroblast growth factor-2, and vascular endothelial growth factor-A. The expression levels of antifibrotic or hepatic regeneration factors were then measured using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The therapeutic effects of ASC-3Dc were determined using a liver fibrosis model induced by thioacetamide. Histological analysis was performed to elucidate the therapeutic mechanism. ASC-3Dc exhibited high levels of hepatocyte growth factor (HGF), IGF-1, stromal cell-derived factor (SDF)-1 genes, and protein expression. In addition, injecting ASC-3Dc significantly prevented hepatic fibrosis and improved liver function in vivo. Moreover, high numbers of ki-67-expressing hepatocytes were detected in the ASC-3Dc-injected livers. Albumin-expressing ASC-3Dc engrafted in fibrotic livers augmented HGF expression. Thus, short-term 3D-cultured ASCs may be a novel alternative to the conventional treatment for liver damage in clinical settings.

scholarly journals Synthesis of embryonic tendon-like tissue by human marrow stromal/mesenchymal stem cells requires a three-dimensional environment and transforming growth factor β3

2010 ◽  
Vol 29 (8) ◽  
pp. 668-677 ◽  
Author(s):  
Zoher Kapacee ◽  
Ching-Yan Chloé Yeung ◽  
Yinhui Lu ◽  
David Crabtree ◽  
David F. Holmes ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Three Dimensional ◽  
Embryonic Tendon

scholarly journals Transforming growth factor beta induced, a new player in the therapeutic effect of mesenchymal stem cells

2018 ◽  
Vol 26 ◽  
pp. S38-S39
Author(s):  
M. Ruiz ◽  
K. Toupet ◽  
G. Fonteneau ◽  
M. Maumus ◽  
C. Jorgensen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Therapeutic Effect ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Growth Factor Beta

scholarly journals Mesenchymal Stem Cells and Transforming Growth Factor-β3 (TGF-β3) to Enhance the Regenerative Ability of an Albumin Scaffold in Full Thickness Wound Healing

2018 ◽  
Vol 9 (4) ◽  
pp. 65 ◽  
Author(s):  
Dale Feldman ◽  
John McCauley
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Surgical Treatment ◽  
Growth Factor ◽  
Healing Rate ◽  
Pressure Ulcers ◽  
Transforming Growth Factor ◽  
Bed Rest ◽  
Full Thickness ◽  
Non Surgical Treatment

Pressure ulcers are one of the most common forms of skin injury, particularly in the spinal cord injured (SCI). Pressure ulcers are difficult to heal in this population requiring at least six months of bed rest. Surgical treatment (grafting) is the fastest recovery time, but it still requires six weeks of bed rest plus significant additional costs and a high recurrence rate. A significant clinical benefit would be obtained by speeding the healing rate of a non-surgical treatment to close to that of surgical treatment (approximately doubling of healing rate). Current non-surgical treatment is mostly inactive wound coverings. The goal of this project was to look at the feasibility of doubling the healing rate of a full-thickness defect using combinations of three treatments, for the first time, each shown to increase healing rate: application of transforming growth factor-β3 (TGF-β3), an albumin based scaffold, and mesenchymal stem cells (MSCs). At one week following surgery, the combined treatment showed the greatest increase in healing rate, particularly for the epithelialization rate. Although the target level of a 100% increase in healing rate over the control was not quite achieved, it is anticipated that the goal would be met with further optimization of the treatment.

scholarly journals Comparison of biotechnological culture of hypoxia-conditioned rat mesenchymal stem cells with conventional in vitro culture of normoxia-conditioned rat mesenchymal stem cells for testicular failure therapy with low libido in rats

2019 ◽  
Vol 12 (6) ◽  
pp. 916-924 ◽  
Author(s):  
Erma Safitri ◽  
Mas'ud Hariadi
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Functional Outcome ◽  
Leydig Cells ◽  
Control Group ◽  
Spermatogenic Cells ◽  
Hematopoietic Stem ◽  
T1 And T2 ◽  
Testicular Failure

Aim: Biotechnological culture of hypoxia-conditioned (CH) rat mesenchymal stem cells (rMSC-CH) for testicular failure therapy with low libido improves the functional outcome of the testicle for producing spermatogenic cells and repairs Leydig cells in rats (Rattus norvegicus). Materials and Methods: In the first group (T1), rats with testicular failure and low libido were injected with normoxia-conditioned (CN) rMSCs (21% oxygen); in the second group (T2), rats with testicular failure and low libido were injected with rMSC-CH (1% oxygen); in the negative control group (T–), rats with normal testis were injected with 0.1 mL phosphate-buffered saline (PBS); and in the sham group (TS), rats with testicular failure and low libido were injected with 0.1 mL of PBS. Results: Vascular endothelial growth factor expression, as the homing signal, in the groups T2, T–, T1, and TS was 2.00±0.5%, 2.95±0.4%, 0.33±0.48%, and 0±0%, respectively. The number of cluster of differentiation (CD)34+ and CD45+ cells in the groups T– and TS was <20%, whereas that in T1 and T2 groups was >30% and >80%, respectively, showing the mobilization of hematopoietic stem cells (HSCs). The number of spermatogenic cells (spermatogonia, primary spermatocytes, secondary spermatocytes, and spermatid) decreased significantly (p<0.05) in TS compared with that in T–, T1, and T2, whereas that in T2 did not show a significant (p>0.05) decrease compared to that in T–. The improvement in libido, based on the number of Leydig cells producing the hormone testosterone for libido expression, did not increase in T1, whereas T2 was able to maintain the number of Leydig cells significantly compared to that between TS and T1. Conclusion: rMSC-CH culture for testicular failure with low libido showed improvement in the functional outcome of the testicle and in repairing Leydig cells.

scholarly journals Clinical efficacy on glycemic control and safety of mesenchymal stem cells in patients with diabetes mellitus: Systematic review and meta-analysis of RCT data

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247662
Author(s):  
Jingjing He ◽  
Desheng Kong ◽  
Zhifen Yang ◽  
Ruiyun Guo ◽  
Asiamah Ernest Amponsah ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Random Effects ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Control Group ◽  
Efficacy And Safety ◽  
Significant Difference

Background Diabetes mellitus as a chronic metabolic disease is threatening human health seriously. Although numerous clinical trials have been registered for the treatment of diabetes with stem cells, no articles have been published to summarize the efficacy and safety of mesenchymal stem cells (MSCs) in randomized controlled trials (RCTs). Methods and findings The aim of this study was to systematically review the evidence from RCTs and, where possible, conduct meta-analyses to provide a reliable numerical summary and the most comprehensive assessment of therapeutic efficacy and safety with MSCs in diabetes. PubMed, Web of Science, Ovid, the Cochrane Library and CNKI were searched. The retrieval time was from establishment of these databases to January 4, 2020. Seven RCTs were eligible for analysis, including 413 participants. Meta-analysis results showed that there were no significant differences in the reduction of fasting plasma glucose (FPG) compared to the baseline [mean difference (MD) = -1.05, 95% confidence interval (CI) (-2.26,0.16), P<0.01, I2 = 94%] and the control group [MD = -0.62, 95%CI (-1.46,0.23), P<0.01, I2 = 87%]. The MSCs treatment group showed a significant decrease in hemoglobin (Hb) A1c [random-effects, MD = -1.32, 95%CI (-2.06, -0.57), P<0.01, I2 = 90%] after treatment. Additionally, HbA1c reduced more significantly in MSC treatment group than in control group [random-effects, MD = -0.87, 95%CI (-1.53, -0.22), P<0.01, I2 = 82%] at the end of follow-up. However, as for fasting C-peptide levels, the estimated pooled MD showed that there was no significant increase [MD = -0.07, 95%CI (-0.30, 0.16), P<0.01, I2 = 94%] in MSCs treatment group compared with that in control group. Notably, there was no significant difference in the incidence of adverse events between MSCs treatment group and control group [relative risk (RR) = 0.98, 95%CI (0.72, 1.32), P = 0.02, I2 = 70%]. The most commonly observed adverse reaction in the MSC treatment group was hypoglycemia (29.95%). Conclusions This meta-analysis revealed MSCs therapy may be an effective and safe intervention in subjects with diabetes. However, due to the limited studies, a number of high-quality as well as large-scale RCTs should be performed to confirm these conclusions.

Sign in / Sign up

Export Citation Format

Share Document