scholarly journals A potential therapy of human umbilical cord mesenchymal stem cells for bone regeneration on osteoporotic mandibular bone

2018 ◽  
Vol 12 (03) ◽  
pp. 358-362
Author(s):  
Nike Hendrijantini ◽  
Tuti Kusumaningsih ◽  
Rostiny Rostiny ◽  
Pungky Mulawardhana ◽  
Coen Pramono Danudiningrat ◽  
...  

ABSTRACTObjective: The aim of this study is to prove that human umbilical cord mesenchymal stem cell (hUCMSC) therapy on mandibular osteoporotic model is able to increase transforming growth factor-beta-1 (TGF)-β1 expression, Runx2, and osteoblasts. Materials and Methods: This research is true experimental posttest control group design. Thirty female Wistar rats were divided into 6 groups randomly, which consisted of sham surgery for control (T1), ovariectomy as osteoporotic group (T2), osteoporotic group injected with gelatine for 4 weeks (T3), 8 weeks (T4) injected with hUCMSC-gelatine for 4 weeks (T5) and 8 weeks (T6). All mice were presented for immunohistochemistry examination for TGF-β1, Runx2, and histology for osteoblasts. Results: The lowest level of osteoblast was osteoporotic group injected with gelatine in 4 weeks compared to other groups. There were increases of TGF-β1, Runx2, and osteoblasts from osteoporotic group compared to osteoporotic post-hUCMSC-gelatine injection group. Conclusion: The hUCMSC has a high osteogenic effect and increases the osteoporotic mandibular bone regeneration on the animal model that is showed by the increase of the level of TGF-β1, Runx2, and osteoblasts.

2019 ◽  
Vol 10 (1) ◽  
pp. 72-80 ◽  
Author(s):  
Tayebeh Mahmoudi ◽  
Kamal Abdolmohammadi ◽  
Hamed Bashiri ◽  
Mehdi Mohammadi ◽  
Mohammad Jafar Rezaie ◽  
...  

Purpose: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder with few available treatments. Mesenchymal stem cell therapy (MSCT), an innovative approach, has high therapeutic potential when used to treat IPF. According to recent data, preconditioning of MSCs can improve their therapeutic effects. Our research focuses on investigating the anti-inflammatory and antifibrotic effects of H2 O2 -preconditioned MSCs (p-MSCs) on mice with bleomycin-induced pulmonary fibrosis (PF). Methods: Eight-week-old male C57BL/6 mice were induced with PF by intratracheal (IT) instillation of bleomycin (4 U/kg). Human umbilical cord vein-derived MSCs (hUCV-MSCs) were isolated and exposed to a sub-lethal concentration (15 μM for 24 h) of H2 O2 in vitro. One week following the injection of bleomycin, 2×105 MSCs or p-MSCs were injected (IT) into the experimental PF. The survival rate and weight of mice were recorded, and 14 days after MSCs injection, all mice were sacrificed. Lung tissue was removed from these mice to examine the myeloperoxidase (MPO) activity, histopathological changes (hematoxylin-eosin and Masson’s trichrome) and expression of transforming growth factor beta 1 (TGF-β1) and alpha-smooth muscle actin (α-SMA) through immunohistochemistry (IHC) staining. Results: Compared to the PF+MSC group, p-MSCs transplantation results in significantly decreased connective tissue (P<0.05) and collagen deposition. Additionally, it is determined that lung tissue in the PF+pMSC group has increased alveolar space (P<0.05) and diminished expression of TGF-β1 and α-SMA. Conclusion: The results demonstrate that MSCT using p-MSCs decreases inflammatory and fibrotic factors in bleomycin-induced PF, while also able to increase the therapeutic potency of MSCT in IPF


2020 ◽  
Vol 4 (1) ◽  
pp. 21-25
Author(s):  
Noor Alhuda K. Ibrahim ◽  
Wasnaa J. Mohammad ◽  
Sanan T. Abdawahab

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women of reproductive age. The aim of the study was to determine the level of apelin, insulin resistance (IR), transforming growth factor beta 1 (TGF-β1), and endoglin in women with polycystic ovary syndrome. Fifty PCOS patients and 40 non-PCOS infertile patients were recruited. The fasting serum levels of folliclestimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), prolactin, fasting blood glucose, insulin, and apelin at the early follicular phase were measured. Levels of apelin, LH, LH/FSH, T, and fasting insulin, as well as homeostatic model assessment of IR (HOMA-IR) in PCOS patients, were significantly higher than in the control group. Correlation analysis showed that apelin level was positively correlated with body mass index and HOMA-IR. Apelin levels and TGF-β1 were significantly increased in PCOS patients while show decrease levels of endoglin.


2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Zhen Yu ◽  
Ye Li ◽  
Yining Wang ◽  
Yuting Chen ◽  
Mengfan Wu ◽  
...  

Abstract Background: Transforming growth factor beta (TGF-β) can stimulate osteogenesis as a multifunctional protein. The present study was to explore if TGF-β can prevent denervation-induced reduction of bone formation. Materials & methods: The 6-week-old male mice were treated with recombinant human TGF-β1 (rhTGF-β1). Bone formation, endochondral bone growth rates, and gene expression of osteoblast markers were measured in the skeletal tissue by real-time PCR. Results: RhTGF-β1 treatment prevented the denervation-induced decrease in bone formation rates, endochondral growth, and expression of Cbfa1/Runx2 (runt-related transcription factor 2), Ostecalcin (OC), and ColIA1. TGF-β1 partially inhibited the denervation-induced ubiquitination of Cbfa1/Runx2 in mouse cancellous bones via ubiquitin-proteasome pathway. Conclusion: TGF-β prevents denervation-induced reduction of bone formation and promotes the bone regeneration through inhibiting ubiquitin-proteasome pathway at least partially.


Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1844
Author(s):  
Marta Rybska ◽  
Magdalena Woźna-Wysocka ◽  
Barbara Wąsowska ◽  
Marek Skrzypski ◽  
Magdalena Kubiak ◽  
...  

Cystic endometrial hyperplasia (CEH) and pyometra are the most frequently diagnosed uterine diseases affecting bitches of different ages. Transforming growth factor beta (TGF-β) has been classified in females as a potential regulator of many endometrial changes during the estrous cycle or may be involved in pathological disorders. The aim of this study was to determine the expression of TGF-β1, -β2 and -β3 in the endometrium of bitches suffering from CEH or a CEH–pyometra complex compared to clinically healthy females (control group; CG). A significantly increased level of TGF-β1 mRNA expression was observed in the endometrium with CEH–pyometra compared to CEH and CG. Protein production of TGF-β1 was identified only in the endometrium of bitches with CEH–pyometra. An increase in TGF-β3 mRNA expression was observed in all the studied groups compared to CG. The expression of TGF-β2 mRNA was significantly higher in CEH and lower in CEH–pyometra uteri. The results indicate the presence of TGF-β cytokines in canine endometrial tissues affected by proliferative and degenerative changes. However, among all TGF-β isoforms, TGF-β1 could potentially be a key factor involved in the regulation of the endometrium in bitches with CEH–pyometra complex.


2020 ◽  
Vol 8 (A) ◽  
pp. 297-301
Author(s):  
Hernita Taurustya ◽  
Mae Sri Hartati Wahyuningsih ◽  
Indwiani Astuti

BACKGROUND: Keloid is a benign fibroproliferative dermis tumor characterized by an increase in growth factors which induce fibroblast proliferation, excessive migration, and synthesis of collagen. Nerium indicum Mill. extract had been studied as a keloid therapy agent. 5α-oleandrin contained in N. indicum has antikeloid activity by inhibiting keloid fibroblast proliferation, fibroblast migration, collagen deposition, and transforming growth factor beta-1 (TGF-β1) synthesis. OBJECTIVE: This study aimed to determine the effect of administration of N. indicum extract on TGF-β1 and vascular endothelial growth factor (VEGF) expression in keloid fibroblast. METHODS: This research was a quasi-experimental research with a post-test only control group design. The research subjects were fibroblast cells passage IV-VII isolated from patients’ keloid tissue with explant techniques. Treatment groups received N. indicum extract with a serial concentration of 2 μg/ml, 1 μg/ml, and 0.5 μg/ml, and control group received medium only. The supernatant was obtained after 72 h incubation period. Examination of TGF-β1 and VEGF expressions was performed using ELISA procedure. RESULT: The expression of TGF-β1 in the treatment groups of the extract N. indicum (2 μg/ml, 1 μg/ml, and 0.5 μg/ml) was significantly lower than a control group of keloid fibroblasts (p < 0.05), according to increased concentration. VEGF expression in the treatment groups of N. indicum extract was lower compared to the control group of keloid fibroblasts. A significant decrease in keloid fibroblast VEGF levels occurred at extract concentrations of 2 μg/ml and 1 μg/ml (p < 0.05). CONCLUSION: N. indicum extract could decrease TGF-β1 and VEGF expressions compared to control medium in keloid fibroblast cultures.


2020 ◽  
Vol 49 (1) ◽  
pp. 79-87
Author(s):  
Hongwei Chen ◽  
Li Chen ◽  
Dongcheng Xie ◽  
Jianxing Niu

Background: Emerging evidence indicates a beneficial effect of mesenchymal stem cell (MSC) transplantation in subarachnoid hemorrhage (SAH). Chronic hydrocephalus is a common complication after SAH, which is associated with subarachnoid fibrosis promoted by transforming growth factor-β1 (TGF-β1). This study investigated the effect of human umbilical cord derived MSCs (hUC-MSCs) with TGF-β1 knockdown on chronic hydrocephalus after SAH. Methods: About 0.5 mL autologous blood was injected into the cerebellomedullaris cistern of 6-week SD rats to establish SAH model. hUC-MSCs or hUC-MSCs carrying TGF-β1 knockdown (1 × 105 cells) were intraventricularly transplanted at 1 day before surgery and at P10. Neurological behavior score and water maze test were performed to assess neurological functions. Hydrocephalus was evaluated by Nissl staining. Concentrations of proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. The levels of TGF-β1, p-Smad2/3, and Smad2/3 were measured using western blotting. Results: Intraventricular hUC-MSCs transplantation significantly attenuated SAH-induced chronic hydrocephalus, upregulation of inflammatory cytokines, and behavioral impairment. Knockdown of TGF-β1 in hUC-MSCs enhanced these effects. hUC-MSCs also reduced the upregulation of TGF-β1 levels and Smad2/3 phosphorylation after SAH, and this effect was also enhanced by TGF-β1 knockdown. Conclusion: Transplantation of hUC-MSCs exerts beneficial effect after SAH, possibly be through inhibiting TGF-β1/Smad2/3 signaling pathway. Knockdown of TGF-β1 in hUC-MSCs enhanced these effects.


2021 ◽  
Vol 11 (4) ◽  
pp. 731-735
Author(s):  
Yuchen Wang ◽  
Zhimin Huang

Gastric cancer (GC) is a common tumor with high incidence and poor prognosis. So far, the pathogenesis of GC has not been fully elucidated, which has brought great difficulty to the treatment. TGF-β regulates cell growth and differentiation. As a key member, TGF-β1 is abnormally expressed in various tumors, but its role on GC and related mechanisms have not been elucidated. Gastric cancer and adjacent tissues were collected to measure TGF-β1 level by real-time PCR. SGC-7901 cell was assigned into control group, mock group, and TGF-β1 siRNA group followed by analysis of TGF-β1 level by ELISA, cell proliferation by MTT assay, apoptosis by flow cytometry, cell migration by cell scratch test, cell invasion by Transwell chamber assay, and Bcl-2, Bax, and PTEN level by Western blot. TGF-β1 was significantly upregulated in GC tissues (P <0.05) and increased with TNM stage dependence. TGF-β1 siRNA transfection significantly decreased TGF-β1 mRNA level and secretion, inhibited cell proliferation, increased apoptosis rate, and attenuated cell migration and invasion along with downregulated Bcl-2 and elevated Bax and PTEN expression (P <0.05). Downregulation of TGF-β1 can promote gastric cancer cell apoptosis, inhibit proliferation, migration, and invasion by regulating PTEN.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Fei Wang ◽  
Xiao-Xia Su ◽  
Yu-Cheng Guo ◽  
Ang Li ◽  
Yin-Cheng Zhang ◽  
...  

In the preliminary study, we have found an excellent osteogenic property of nanohydroxyapatite/chitosan/poly(lactide-co-glycolide) (nHA/CS/PLGA) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUCMSCs)in vitroand subcutaneously in the nude mice. The aim of this study was to further evaluate the osteogenic capacity of nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice. Totally 108 nude mice were included and divided into 6 groups: PLGA scaffolds + hUCMSCs; nHA/PLGA scaffolds + hUCMSCs; CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds + hUCMSCs; nHA/CS/PLGA scaffolds without seeding; the control group (no scaffolds) (n=18). The scaffolds were implanted into the calvarial defects of nude mice. The amount of new bones was evaluated by fluorescence labeling, H&E staining, and Van Gieson staining at 4 and 8 weeks, respectively. The results demonstrated that the amount of new bones was significantly increased in the group of nHA/CS/PLGA scaffolds seeded with hUCMSCs (p<0.01). On the basis of previous studiesin vitroand in subcutaneous implantation of the nude mice, the results revealed that the nHA and CS also enhanced the bone regeneration by nHA/CS/PLGA scaffolds seeded with hUCMSCs in the calvarial defects of the nude mice at early stage.


2020 ◽  
Vol 22 (4) ◽  
pp. 159-166
Author(s):  
Armita Balash ◽  
Abbas Doosti

Background and aims: The role of Helicobacter pylori in the development of gastric ulcer and gastrointestinal cancer was identified in this study. More precisely, the study focused on the creation of a DNA vaccine based on the cagT gene of this bacterium and the investigation of its immunogenicity against H. pylori in infused BALB/c mice. Materials and Methods: To this end, the pcDNA3.1(+)-cagT was prepared and transformed into Escherichia coli. Then, animals were injected with recombinant pcDNA3.1(+)-cagT plasmid, pcDNA3.1(+)-cagT + nanoparticles, and pcDNA3.1(+). After the plasmid purification and confirmation of the transformation by digestion and polymerase chain reaction (PCR), chitosan nanoparticles were synthesized using the ionic gelation method. Next, the animals were classified into three groups each including 21 mice. The injectable solutions including pcDNA3.1(+)-cagT, pcDNA3.1(+)-cagT + nanoparticles, or empty pCDNA3.1 (as a control group) were injected into the quadriceps muscle of mice, separately. Finally, the blood and tissue samples of each mouse were collected 15, 30, and 45 days after the last injection, and the expression levels of transforming growth factor-beta (TGF-β1), interleukin-4 (IL-4), and interferon-gamma (IFNγ) were evaluated by real-time PCR. Results: The IFNγ and TGF-β1 expression increased in the infused mice (P<0.01) while the IL4 expression represented a significant decrease (P<0.01). Moreover, the IFNγ and IL4 expression level in pcDNA3.1(+)-cagT + nanoparticle significantly altered (P<0.01) compared to the pcDNA3.1(+)-cagT group although the TGF-β1 expression was not significantly different (P=0.075). Contrarily, the cagT gene expression in the tissue samples of both groups was significantly different 15, 30, and 45 days after the last injection (P<0.01). Eventually, the expression of the cagT gene in the infused mice by pcDNA3.1(+)-cagT and in the nanoparticle group was not significantly different 45 days after the last injection (P=0.105). Conclusion: In general, the decrease of IL-4 expression was observed in the injected mice by pcDNA3.1(+)-cagT and indicated that the immune system work by a Th1 pattern. The findings showed that a pcDNA3.1(+)-cagT construct combined with chitosan nanoparticles can increase the stimulation of the immune system in an animal model and thus it can be used as an appropriate method for controlling H. pylori infection.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Tuan Van Nguyen ◽  
Ky Duc Ngo ◽  
Minh Hoang Thi ◽  
Lan Thi Phuong Dam ◽  
Thuan Quang Huynh

Background: The transforming growth factor-beta 1 (TGF-β1) has been demonstrated as one of the main factors in the progression of fibrosis and sclerosis glomerular damages. Glomerulonephritis is one common cause of chronic kidney disease (CKD) with the promotion of inflammatory renal damage containing fibrosis and sclerosis glomerular. Objectives: This study aimed to evaluate the TGF-β1 level in CKD patients and compare it with the healthy control group. Methods: This cross-sectional case-control study was carried out on 212 subjects admitted to the Nghe An Friendship General Hospital in Vietnam from March 2018 to February 2020. The case group included 152 patients diagnosed with CKD caused by glomerulonephritis, and the control group included 60 healthy individuals. The TGF-β1 was determined in serum by ELISA method. Results: The serum TGF-β1 concentration of the healthy control group and CKD group was 13.45 ± 7.17 and 32.35 ± 11.74, respectively. The CKD group had a significantly higher TGF-β1 level than the control group (P < 0.05). The CKD group with the eGRP ≥ 60 mL/min/1.73 m2 group had a higher TGF-β1 level than the eGRP < 60 mL/min/1.73 m2 group, and the TGF-β1 level increased from stage 1 to stage 5 (P < 0.001). The TGF-β1 had a medium correlation to urea, creatinine, and hs-CRP. Conclusions: The concentration of TGF-β1 in the CKD group was higher than the control group so that it increased early from the first stage of the disease.


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