|
1
|
AlJunaydil NA, Lambarte RNA, Sumague TS, Alghamdi OG, Niazy AA. Lovastatin and Resveratrol Synergistically Improve Wound Healing and Inhibit Bacterial Growth. Int J Mol Sci 2025; 26:851. [PMID: 39859566 PMCID: PMC11766293 DOI: 10.3390/ijms26020851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 01/14/2025] [Accepted: 01/16/2025] [Indexed: 01/27/2025] Open
Abstract
Wound healing is a complex physiological process, with scarring and infection caused by Staphylococcus aureus and Pseudomonas aeruginosa being the most common complications. The reutilization of known medications has received increased attention for their role in cell function as small molecules. Examples of these include lovastatin, a cholesterol-lowering agent, and resveratrol, which have multiple biological properties. Both molecules have been reported to improve wound healing and possess antibacterial properties, with conflicting results. The wound-healing capabilities of human mesenchymal stem cells were evaluated after exposure to lovastatin, resveratrol, and their combination through scratch test, migrations assay, and qPCR. Protein docking was performed to assess the lovastatin/resveratrol combination as potential wound-healing targets. AlamarBlue assay was used to determine cell viability. Additionally, the impact of lovastatin and resveratrol combination to inhibit the growth of S. aureus and P. aeruginosa was tested using broth microdilution test and checkerboard assay to determine synergism. The combination of lovastatin 0.1 μM and resveratrol 0.1 μM synergistically improved wound healing and demonstrated an additive effect against S. aureus and P. aeruginosa, presenting potential antibacterial applications.
Collapse
Affiliation(s)
- Norah A. AlJunaydil
- Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh 11451, Saudi Arabia; (N.A.A.); (O.G.A.)
| | - Rhodanne Nicole A. Lambarte
- Molecular and Cell Biology Laboratory, Prince Naif bin Abdulaziz Health Research Center, College of Dentistry, King Saud University Medical City, King Saud University, Riyadh 11545, Saudi Arabia; (R.N.A.L.); (T.S.S.)
| | - Terrence S. Sumague
- Molecular and Cell Biology Laboratory, Prince Naif bin Abdulaziz Health Research Center, College of Dentistry, King Saud University Medical City, King Saud University, Riyadh 11545, Saudi Arabia; (R.N.A.L.); (T.S.S.)
| | - Osama G. Alghamdi
- Department of Oral and Maxillofacial Surgery, College of Dentistry, King Saud University, Riyadh 11451, Saudi Arabia; (N.A.A.); (O.G.A.)
| | - Abdurahman A. Niazy
- Molecular and Cell Biology Laboratory, Prince Naif bin Abdulaziz Health Research Center, College of Dentistry, King Saud University Medical City, King Saud University, Riyadh 11545, Saudi Arabia; (R.N.A.L.); (T.S.S.)
- Department of Oral Medicine and Diagnostic Sciences, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia
| |
Collapse
|
|
2
|
Romão CM, de Lara Janz F, Ruiz JLM, Lopes MAB, Cristante AF, de Barros Filho TEP, Levy D, Bydlowski SP. Expression of ABCB1, ABCC1, and LRP in Mesenchymal Stem Cells from Human Amniotic Fluid and Bone Marrow in Culture-Effects of In Vitro Osteogenic and Adipogenic Differentiation. Int J Mol Sci 2025; 26:510. [PMID: 39859227 PMCID: PMC11765172 DOI: 10.3390/ijms26020510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 12/27/2024] [Accepted: 01/06/2025] [Indexed: 01/27/2025] Open
Abstract
Mesenchymal stem cells (MSCs) are multipotent cells with the potential to differentiate into various lineages. They have also the potential to protect themselves against harmful stimuli to maintain their functional integrity. Drug resistance-related transporters such as ABCB1 (P-glycoprotein; P-gp), ABCC1 (MRP1; multidrug resistance-related Protein 1), and LRP (lung resistance protein) may protect MSCs against toxic substances such as chemotherapeutic agents. This study evaluated ABCB1, ABCC1, and LRP before and after the differentiation of MSCs derived from human amniotic fluid (AF) and bone marrow (BM). P-gp expression in both AFMSCs and BMMSCs was analyzed by immunocytochemistry, and pump function was analyzed by cell viability assay with doxorubicin (DOX) and Rhodamine 123 (Rh 123) dye exclusion. ABCB1, ABCC1, and LRP gene expression was determined by RT-PCR both before and after osteogenic and adipogenic differentiation. The MES-SA/DX5 cell line was used as a model of resistance to DOX and the overexpression of P-gp. Both AFMSCs and BMMSCs displayed a high P-gp expression, although lower than MES-SA/DX5 control cells. It was shown that both, undifferentiated AFMSCs and BMMSCs, have high cell viability in response to DOX, similar to the MES-SA/DX5 lineage. ABCB1 was less expressed in BM than in AFMSCs in undifferentiated samples, while no differences were observed in the expression of ABCC1 and LRP. AFMSCs showed an increase in ABCB1 after osteogenic differentiation, whereas BMMSCs exhibited lower ABCB1 and ABCC1 expression after osteogenic and adipogenic differentiation. The findings suggest that ABCB1, ABCC1, and LRP gene expression in AFMSCs and BMMSCs is influenced by differentiation processes and further support the concept that these transporters modulate MSC differentiation in a cell source-dependent way.
Collapse
Affiliation(s)
- Carolina Martinez Romão
- Lipids, Oxidation, and Cell Biology Group, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo 05403-900, Brazil; (C.M.R.); (D.L.)
- Hospital Sírio-Libanês, São Paulo 01308-050, Brazil
| | - Felipe de Lara Janz
- General Biology Department, State University of Ponta Grossa (UEPG), Ponta Grossa 84010-330, Brazil;
| | - Jorge Luis Maria Ruiz
- Latin American Institute of Life and Natural Sciences, Federal University for Latin American Integration (UNILA), Foz do Iguaçu 85870-650, Brazil;
| | - Marco Antônio Borges Lopes
- Laboratory of Obstetric Physiology, Department of Obstetrics and Gynecology, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 01246-903, Brazil;
| | - Alexandre Fogaça Cristante
- Department of Orthopedics and Traumatology, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05402-000, Brazil; (A.F.C.); (T.E.P.d.B.F.)
| | - Tarcísio Eloy Pessoa de Barros Filho
- Department of Orthopedics and Traumatology, Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo 05402-000, Brazil; (A.F.C.); (T.E.P.d.B.F.)
| | - Débora Levy
- Lipids, Oxidation, and Cell Biology Group, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo 05403-900, Brazil; (C.M.R.); (D.L.)
| | - Sérgio Paulo Bydlowski
- Lipids, Oxidation, and Cell Biology Group, Laboratory of Immunology (LIM19), Heart Institute (InCor), Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo (HCFMUSP), São Paulo 05403-900, Brazil; (C.M.R.); (D.L.)
- National Institute of Science and Technology in Regenerative Medicine (INCT-Regenera), CNPq, Rio de Janeiro 21941-902, Brazil
| |
Collapse
|
|
3
|
Li S, Wang J, Jiang B, Jiang J, Luo L, Zheng B, Si W. Mesenchymal stem cells derived from different perinatal tissues donated by same donors manifest variant performance on the acute liver failure model in mouse. Stem Cell Res Ther 2022; 13:231. [PMID: 35659084 PMCID: PMC9166497 DOI: 10.1186/s13287-022-02909-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2022] [Accepted: 04/16/2022] [Indexed: 01/30/2023] Open
Abstract
Background Mesenchymal stem cells (MSCs) derived from different tissues have variant biological characteristics, which may induce different performances in the treatment of diseases. At present, it is difficult to know which type of MSC is most suitable for acute liver failure (ALF), and there is no parallel study to compare MSCs from different tissues of the same donor. Methods In this study, we derived MSCs from three different perinatal tissues of the same donor: cord lining (CL), cord–placenta junction (CPJ) and fetal placenta (FP), respectively, for compared gene expression profiles by transcriptome sequencing, and ability of proliferation and immune regulation in vitro. In addition, the therapeutic effects (e.g., survival rate, histological evaluation, biochemical analysis) of CL-MSCs, FP-MSCs and CPJ-MSCs on ALF mouse model were compared. Results The transcriptome analysis showed that FP-MSCs have significantly high expression of chemokines compared to CPJ-MSCs and CL-MSCs, similar to the q-PCR result. Of note, we found that CPJ-MSCs and FP-MSCs could improve the survival rate of mice with ALF induced by carbon tetrachloride, but CL-MSCs had no difference with Sham group. Moreover, we also found that biomarkers of ALF (e.g., MDA, SOD and GSH-px) significantly improved post-CPJ-MSCs and FP-MSCs treatment, but not CL-MSCs and Sham group. However, CL-MSCs treatment leads to inflammatory reaction in the early stage (day 3) of ALF treatment but not found with other groups. Conclusions It is important to select the MSCs derived from different tissues with variant performance for therapeutic purpose, and the CPJ-MSCs and FP-MSCs cells can significantly improve the syndrome of ALF which is highly recommended for a potential therapeutic options for ALF. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-022-02909-w.
Collapse
Affiliation(s)
- Shanshan Li
- School of Medicine, Yunnan University, Kunming, 650000, Yunnan, China.,State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650000, China
| | - Junfeng Wang
- Department of Hepatic and Bile Duct Surgery, The First People's Hospital of Yunnan Province, Kunming, 650000, China
| | - Bin Jiang
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650000, China
| | - Jiang Jiang
- Department of Obstetrics, The First People's Hospital of Yunnan Province, Kunming, 650000, China
| | - Lilin Luo
- Department of Pathology, The First People's Hospital of Yunnan Province, Kunming, 650000, China
| | - Bingrong Zheng
- School of Medicine, Yunnan University, Kunming, 650000, Yunnan, China.
| | - Wei Si
- State Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, 650000, China.
| |
Collapse
|
|
4
|
Gorabi AM, Kiaie N, Pirro M, Bianconi V, Jamialahmadi T, Sahebkar A. Effects of statins on the biological features of mesenchymal stem cells and therapeutic implications. Heart Fail Rev 2021; 26:1259-1272. [PMID: 32008148 DOI: 10.1007/s10741-020-09929-9] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Statins are well-known lipid-lowering drugs. The pleiotropic effects of statins have brought about some beneficial effects on improving the therapeutic outcomes of cell therapy and tissue engineering approaches. In this review, the impact of statins on mesenchymal stem cell behaviors including differentiation, apoptosis, proliferation, migration, and angiogenesis, as well as molecular pathways which are responsible for such phenomena, are discussed. A better understanding of pathways and mechanisms of statin-mediated effects on mesenchymal stem cells will pave the way for the expansion of statin applications. Furthermore, since designing a suitable carrier for statins is required to maintain a sufficient dose of active statins at the desired site of the body, different systems for local delivery of statins are also reviewed.
Collapse
Affiliation(s)
- Armita Mahdavi Gorabi
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Nasim Kiaie
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Matteo Pirro
- Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy
| | - Vanessa Bianconi
- Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy
| | - Tannaz Jamialahmadi
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Halal Research Center of IRI, FDA, Tehran, Iran.
- Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
5
|
Gan Z, Song Y, Zhang H, Ye Y, Chu H. WITHDRAWN: MiR-363-3p attenuates simvastatin-induced osteogenic differentiation of periodontal ligament stem cells by targeting KLF2. Tissue Cell 2021. [DOI: 10.1016/j.tice.2021.101629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
|
|
6
|
Senel U, Coskun OS, Tuysuz EC, Sahin M, Bayrak OF, Cakmak B, Tanriverdi HI, Kuskucu A. Smooth muscle cell differentiation from rabbit amniotic cells. Exp Mol Pathol 2018; 105:395-403. [PMID: 30414978 DOI: 10.1016/j.yexmp.2018.11.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Revised: 07/14/2018] [Accepted: 11/06/2018] [Indexed: 11/25/2022]
Abstract
Amniotic fluid (AF) is the liquid layer that provides mechanical support and allows movement of the fetus during embryogenesis. Mesenchymal stem cells (MSCs), which have differentiation capacity, are also found in AF-derived cells at a low ratio. Smooth muscle cells (SMCs) play an important role in organ function and are frequently used in tissue engineering. We examined the differentiation of AF-derived MSCs (AMSCs) into SMCs. AMSCs were sorted from cultured amniotic cells and differentiated into SMCs using differentiation agents, including platelet-derived growth factor BB (PDGF-BB) and tumor growth factor β (TGF-β). Characterization of differentiated SMCs was confirmed morphologically, molecularly (via quantitative polymerase chain reaction [qPCR] and immunocytochemistry [ICC]), and functionally (using a contractile assay and fluo-4 calcium signaling assay). Poly(lactide-co-glycolide) (PLGA) scaffolds were fabricated, and the attachment capacity of AMSCs was assessed via scanning electron microscopy. AMSCs were successfully differentiated into SMCs. Our results indicate that AMSCs change their morphology and exhibit increased expression of ACTA2 and MYH11, which was confirmed via qPCR and ICC. Furthermore, functional experiments revealed that differentiated SMCs had both contraction ability and increased Ca2 concentration in the cytoplasm. Finally, PLGA scaffolds were prepared and AMSCs were successfully planted onto the scaffolds. The AMSCs fully differentiated into functional SMCs, and the PLGA polymer is a suitable scaffold material for AMSCs. With further clinical trials, AF-derived MSC-based SMC engineering may become a highly efficient treatment option.
Collapse
Affiliation(s)
- Ufuk Senel
- Department of Pediatric Surgery, Faculty of Medicine, Gaziosmanpasa University, 60100 Tokat, Turkey
| | - Ozlem Silan Coskun
- Department of Medical Genetics, Yeditepe University Medical School, 34755 Istanbul, Turkey; Department of Biotechnology, Institute of Science, Yeditepe University, 34755 Istanbul, Turkey
| | - Emre Can Tuysuz
- Department of Medical Genetics, Yeditepe University Medical School, 34755 Istanbul, Turkey; Department of Biotechnology, Institute of Science, Yeditepe University, 34755 Istanbul, Turkey
| | - Mesut Sahin
- Department of Nanoscience and Nanoengineering, Institute of Science Ataturk University, 25240 Erzurum, Turkey
| | - Omer Faruk Bayrak
- Department of Medical Genetics, Yeditepe University Medical School, 34755 Istanbul, Turkey
| | - Bulent Cakmak
- Department of Obstetrics and Gynecology, Faculty of Medicine, Gaziosmanpasa University, 60100 Tokat, Turkey
| | - Halil Ibrahim Tanriverdi
- Department of Pediatric Surgery, Faculty of Medicine, Gaziosmanpasa University, 60100 Tokat, Turkey
| | - Aysegul Kuskucu
- Department of Medical Genetics, Yeditepe University Medical School, 34755 Istanbul, Turkey.
| |
Collapse
|
|
7
|
Wang J, Wang F, Wang Z, Li S, Chen L, Liu C, Sun D. Protective effect of GDNF-engineered amniotic fluid-derived stem cells on the renal ischaemia reperfusion injury in vitro. Cell Prolif 2017; 51:e12400. [PMID: 29114949 DOI: 10.1111/cpr.12400] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2017] [Accepted: 09/25/2017] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVES Amniotic fluid-derived stem cells (AFSCs) possessing multilineage differentiation potential are proposed as a novel and accessible source for cell-based therapy and tissue regeneration. Glial-derived neurotrophic factor (GDNF) has been hypothesized to promote the therapeutic effect of AFSCs on markedly ameliorating renal dysfunction. The aim of this study was to investigate whether AFSCs equipped with GDNF (GDNF-AFSCs) had capabilities of attenuating mouse renal tubular epithelial cells (mRTECs) apoptosis and evaluate its potential mechanisms. MATERIALS AND METHODS A hypoxia-reoxygenation (H/R) model of the mRTECs was established. Injured mRTECs were co-cultured with GDNF-AFSCs in a transwell system. The mRNA expressions of hepatocytes growth factor (HGF) and fibroblast growth factor (bFGF) were detected by qRT-PCR. Changes of intracelluar reactive oxygen species (ROS) and the level of superoxide dismutase (SOD) and malondialdehyde (MDA) were examined. The expressions of nitrotyrosine, Gp91-phox, Bax, and Bcl-2 were determined by Western blotting. Cell apoptosis was assayed by flow cytometry, and caspase-3 activity was monitored by caspase-3 activity assay kit. RESULTS Our study revealed that expression of growth factors was increased and oxidative stress was dramatically counteracted in GDNF-AFSCs-treated group. Furthermore, apoptosis induced by H/R injury was inhibited in mRTECs by GDNF-AFSCs. CONCLUSIONS These data indicated that GDNF-AFSCs are beneficial to repairing damaged mRTECs significantly in vitro, which suggests GDNF-AFSCs provide new hopes of innovative interventions in different kidney disease.
Collapse
Affiliation(s)
- Jia Wang
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Fengzhen Wang
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.,Department of Pharmaceutics, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Zhuojun Wang
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Shulin Li
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Lu Chen
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Caixia Liu
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
| | - Dong Sun
- Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.,Department of Internal Medicine and Diagnostics, Xuzhou Medical University, Xuzhou, China
| |
Collapse
|
|
8
|
Osteogenic Differentiation of Human Amniotic Fluid Mesenchymal Stem Cells Is Determined by Epigenetic Changes. Stem Cells Int 2016; 2016:6465307. [PMID: 27818691 PMCID: PMC5080506 DOI: 10.1155/2016/6465307] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Accepted: 09/19/2016] [Indexed: 12/30/2022] Open
Abstract
Osteogenic differentiation of human amniotic fluid derived mesenchymal stem cells (AF-MSCs) has been widely studied in vitro and in vivo as a potential tool for regenerative medicine and tissue engineering. While most of the studies analyze changes in transcriptional profile during differentiation to date there is not much information regarding epigenetic changes in AF-MSCs during differentiation. The aim of our study was to evaluate epigenetic changes during osteogenic differentiation of AF-MS cells. Isolated AF-MSCs were characterized morphologically and osteogenic differentiation was confirmed by cell staining and determining expression of alkaline phosphatase and osteopontin by RT-qPCR. Variation in gene expression levels of pluripotency markers and specific microRNAs were also evaluated. Analysis of epigenetic changes revealed that levels of chromatin modifying enzymes such as Polycomb repressive complex 2 (PRC2) proteins (EZH2 and SUZ12), DNMT1, HDAC1, and HDAC2 were reduced after osteogenic differentiation of AF-MSCs. We demonstrated that the level of specific histone markers keeping active state of chromatin (H3K4me3, H3K9Ac, and others) increased and markers of repressed state of chromatin (H3K27me3) decreased. Our results show that osteogenic differentiation of AF-MSCs is conducted by various epigenetic alterations resulting in global chromatin remodeling and provide insights for further epigenetic investigations in human AF-MSCs.
Collapse
|
|
9
|
Zhang W, Wang S, Yin H, Chen E, Xue D, Zheng Q, Gao X, Pan Z. Dihydromyricetin enhances the osteogenic differentiation of human bone marrow mesenchymal stem cells in vitro partially via the activation of Wnt/β-catenin signaling pathway. Fundam Clin Pharmacol 2016; 30:596-606. [PMID: 27469984 DOI: 10.1111/fcp.12225] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2016] [Revised: 07/06/2016] [Accepted: 07/26/2016] [Indexed: 01/06/2023]
Abstract
Substantial evidence has demonstrated that the decreased osteogenic differentiation of bone mesenchymal stem cells (BMSCs) is closely related to bone metabolic diseases. Thus, it is very important to develop several potentially useful therapeutic agents to enhance BMSC osteogenesis. Flavonoids show promise in enhancing bone mass. Dihydromyricetin (DMY), a type of flavonoid, has not yet been investigated regarding its effects on BMSC osteogenesis. To investigate the effects of DMY on osteogenesis, human BMSCs were induced with or without DMY. We found that DMY (0.1-50 μm) exhibited no cytotoxic effect on proliferation, but increased alkaline phosphatase activity, osteoblast-specific gene expression, and mineral deposition. It also enhanced active β-catenin expression and reduced dickkopf-1(DKK1) and sclerostin expression. The Wnt/β-catenin signaling pathway inhibitor (DKK1 and β-catenin-specific siRNA) decreased the enhanced bone mineral formation caused by DMY. Taken together, these findings reveal that DMY enhances osteogenic differentiation of human BMSCs partly through Wnt/β-catenin in vitro.
Collapse
Affiliation(s)
- Wei Zhang
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Shengdong Wang
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Houfa Yin
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Erman Chen
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Deting Xue
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Qiang Zheng
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Xiang Gao
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| | - Zhijun Pan
- Department of Orthopedics, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China
| |
Collapse
|
|
10
|
Simvastatin Protects Osteoblasts from the Deleterious Effects of the Liquid Milieu of Multiple Myeloma. W INDIAN MED J 2015; 64:263-5. [PMID: 26426180 DOI: 10.7727/wimj.2014.227] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2014] [Accepted: 10/29/2014] [Indexed: 01/16/2023]
Abstract
Lytic bone lesions are the main clinical manifestation of multiple myeloma. The intense variety in this cell microenvironment, composed mainly of fibroblasts, osteoblasts, osteoclasts, immune cells and mesenchymal cells, is influenced by the massive presence of neoplastic plasma cells. Studies with statins have reported their action in stimulating the formation and reducing bone resorption. The aim of this study was to verify the in vitro response of human osteoblasts exposed to the supernatant (liquid milieu) of multiple myeloma. The data obtained indicate that simvastatin has positive effects on the growth of osteoblasts and protection against the anti-proliferative effects of multiple myeloma supernatant.
Collapse
|
|
11
|
Pipino C, Pandolfi A. Osteogenic differentiation of amniotic fluid mesenchymal stromal cells and their bone regeneration potential. World J Stem Cells 2015; 7:681-690. [PMID: 26029340 PMCID: PMC4444609 DOI: 10.4252/wjsc.v7.i4.681] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2014] [Revised: 01/16/2015] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
In orthopedics, tissue engineering approach using stem cells is a valid line of treatment for patients with bone defects. In this context, mesenchymal stromal cells of various origins have been extensively studied and continue to be a matter of debate. Although mesenchymal stromal cells from bone marrow are already clinically applied, recent evidence suggests that one may use mesenchymal stromal cells from extra-embryonic tissues, such as amniotic fluid, as an innovative and advantageous resource for bone regeneration. The use of cells from amniotic fluid does not raise ethical problems and provides a sufficient number of cells without invasive procedures. Furthermore, they do not develop into teratomas when transplanted, a consequence observed with pluripotent stem cells. In addition, their multipotent differentiation ability, low immunogenicity, and anti-inflammatory properties make them ideal candidates for bone regenerative medicine. We here present an overview of the features of amniotic fluid mesenchymal stromal cells and their potential in the osteogenic differentiation process. We have examined the papers actually available on this regard, with particular interest in the strategies applied to improve in vitro osteogenesis. Importantly, a detailed understanding of the behavior of amniotic fluid mesenchymal stromal cells and their osteogenic ability is desirable considering a feasible application in bone regenerative medicine.
Collapse
|
|
12
|
Cunha JD, Maselli LMF, Stern ACB, Spada C, Bydlowski SP. Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs. World J Virol 2015; 4:56-77. [PMID: 25964872 PMCID: PMC4419122 DOI: 10.5501/wjv.v4.i2.56] [Citation(s) in RCA: 94] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2014] [Revised: 01/15/2015] [Accepted: 03/09/2015] [Indexed: 02/05/2023] Open
Abstract
For human immunodeficiency virus (HIV)-infected patients, the 1990s were marked by the introduction of highly active antiretroviral therapy (HAART) representing a new perspective of life for these patients. The use of HAART was shown to effectively suppress the replication of HIV-1 and dramatically reduce mortality and morbidity, which led to a better and longer quality of life for HIV-1-infected patients. Apart from the substantial benefits that result from the use of various HAART regimens, laboratory and clinical experience has shown that HAART can induce severe and considerable adverse effects related to metabolic complications of lipid metabolism, characterized by signs of lipodystrophy, insulin resistance, central adiposity, dyslipidemia, increased risk of cardiovascular disease and even an increased risk of atherosclerosis. New drugs are being studied, new therapeutic strategies are being implemented, and the use of statins, fibrates, and inhibitors of intestinal cholesterol absorption have been effective alternatives. Changes in diet and lifestyle have also shown satisfactory results.
Collapse
|
|
13
|
El Omar R, Beroud J, Stoltz JF, Menu P, Velot E, Decot V. Umbilical cord mesenchymal stem cells: the new gold standard for mesenchymal stem cell-based therapies? TISSUE ENGINEERING PART B-REVIEWS 2014; 20:523-44. [PMID: 24552279 DOI: 10.1089/ten.teb.2013.0664] [Citation(s) in RCA: 223] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Due to their self-renewal capacity, multilineage differentiation potential, paracrine effects, and immunosuppressive properties, mesenchymal stromal cells (MSCs) are an attractive and promising tool for regenerative medicine. MSCs can be isolated from various tissues but despite their common immunophenotypic characteristics and functional properties, source-dependent differences in MSCs properties have recently emerged and lead to different clinical applications. Considered for a long time as a medical waste, umbilical cord appears these days as a promising source of MSCs. Several reports have shown that umbilical cord-derived MSCs are more primitive, proliferative, and immunosuppressive than their adult counterparts. In this review, we aim at synthesizing the differences between umbilical cord MSCs and MSCs from other sources (bone marrow, adipose tissue, periodontal ligament, dental pulp,…) with regard to their proliferation capacity, proteic and transcriptomic profiles, and their secretome involved in their regenerative, homing, and immunomodulatory capacities. Although umbilical cord MSCs are until now not particularly used as an MSC source in clinical practice, accumulating evidence shows that they may have a therapeutic advantage to treat several diseases, especially autoimmune and neurodegenerative diseases.
Collapse
Affiliation(s)
- Reine El Omar
- 1 CNRS UMR UL 7365 , Bâtiment Biopôle, Faculté de médecine, Vandœuvre-lès-Nancy, France
| | | | | | | | | | | |
Collapse
|
|
14
|
Machado WM, Prestes AP, Costa TP, Mendes RT, Olchanheski LR, Sordi R, Otuki MF, Fávero GM, Vellosa JCR, Santos FA, Fernandes D. The effect of simvastatin on systemic inflammation and endothelial dysfunction induced by periodontitis. J Periodontal Res 2013; 49:634-41. [DOI: 10.1111/jre.12145] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/30/2013] [Indexed: 12/18/2022]
Affiliation(s)
- W. M. Machado
- Department of Pharmaceutical Sciences; Universidade Estadual de Ponta Grossa; Ponta Grossa PR Brazil
| | - A. P. Prestes
- Department of Pharmaceutical Sciences; Universidade Estadual de Ponta Grossa; Ponta Grossa PR Brazil
| | - T. P. Costa
- Department of Pharmaceutical Sciences; Universidade Estadual de Ponta Grossa; Ponta Grossa PR Brazil
| | - R. T. Mendes
- Department of Dentistry; Universidade Estadual de Ponta Grossa; Ponta Grossa PR Brazil
| | - L. R. Olchanheski
- Department of Pharmaceutical Sciences; Universidade Estadual de Ponta Grossa; Ponta Grossa PR Brazil
| | - R. Sordi
- Department of Pharmacology; Universidade Federal de Santa Catarina; Florianópolis SC Brazil
| | - M. F. Otuki
- Department of Pharmaceutical Sciences; Universidade Estadual de Ponta Grossa; Ponta Grossa PR Brazil
| | - G. M. Fávero
- Department of General Biology; Universidade Estadual de Ponta Grossa; Ponta Grossa PR Brazil
| | - J. C. R. Vellosa
- Department of Clinical and Toxicological Analysis; Universidade Estadual de Ponta Grossa; Ponta Grossa PR Brazil
| | - F. A. Santos
- Department of Dentistry; Universidade Estadual de Ponta Grossa; Ponta Grossa PR Brazil
| | - D. Fernandes
- Department of Pharmaceutical Sciences; Universidade Estadual de Ponta Grossa; Ponta Grossa PR Brazil
| |
Collapse
|