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Agung Putra
Faculty of Medicine Universitas Islam Sultan Agung, Semarang
Agriculture, Biological Sciences & Forestry Biochemistry, Genetics & Molecular Biology Chemistry Computer Science & IT Decision Sciences, Operations Research & Management Dentistry Earth & Planetary Sciences Economics, Econometrics & Finance Education Health Professions Immunology & microbiology Materials Science & Nanotechnology Medicine & Pharmacology Neuroscience Nursing Physics Public Health Social Sciences Other

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Journal : Universa Medicina

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Hypoxia enhances self-renewal properties and markers of mesenchymal stem cells Yustianingsih, Vivi; Sumarawati, Titiek; Putra, Agung
Universa Medicina Vol 38, No 3 (2019)
Publisher : Faculty of Medicine, Trisakti University

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (668.593 KB) | DOI: 10.18051/UnivMed.2019.v38.164-171

Abstract

BackgroundMesenchymal stem cells (MSCs) are multipotent stromal cells that express CD73, CD90, and CD105 surface markers, but not CD14, CD45, CD34, CD11b, and HLA-DR. MSCs under hypoxic conditions have the essential role of maintaining the stemness capacity by releasing several growth factors into their medium, known as hypoxia conditioned medium (HCM). This study was performed to compare the effect of percentage of HCM to normoxic medium (NM) in increasing MSC proliferation marked by proliferation rate and surface marker expression.MethodsThis study was of post-test only control group design using human umbilical cord-MSCs (hUC-MSCs) as subjects. The HCM treatment group was obtained by culturing MSCs under 5% O2, whereas the NM control group was grown under 20% O2. The hUC-MSCs were divided into 4 groups with different dose ratios of HCM to NM (25%:75%; 50%:50%; 75%:25% for P1, P2 and P3, respectively and 100% of NM for the controls). All of these groups were maintained at 37oC and the data was collected after 72 hours incubation. MSC marker expression of CD73, CD90 and CD105 was analyzed using flow cytometry and MSC proliferation by trypan blue assay. ResultThere were significant differences in MSC marker expression of CD73, CD90 and CD105 and proliferation at all dose ratios of HCM to NM (p<0.05).ConclusionLow oxygen concentration promotes MSC proliferation and stemness thus it might be beneficial for maintaining the MSC physiologic niche in-vitro.
Hypoxia-preconditioned mesenchymal stem cells attenuate peritoneal adhesion through TGF-β inhibition Trisnadi, Setyo; Muhar, Adi Muradi; Putra, Agung; Kustiyah, Azizah Retno
Universa Medicina Vol 39, No 2 (2020)
Publisher : Faculty of Medicine, Trisakti University

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1708.691 KB) | DOI: 10.18051/UnivMed.2020.v39.97-104

Abstract

BackgroundPeritoneal adhesions (PAs) are generally described as fibrous bands between intra-abdominal organs following an abdominal surgical operation. The definitive treatments of PAs are currently ineffective yet. Hypoxia-mesenchymal stem cells (H-MSCs) have a higher capability to survive at the site of injury than normoxia-MSCs (N-MSCs) to repair injured tissue without fibrosis. This study aimed to analyze the effect of H-MSCs in controlling formation of PAs by reducing TGF-β level in a rat model. Methods A study of post-test only control group design was conducted, involving eighteen PA rat models weighing 250 ± 25 g that were randomly assigned into 3 groups, comprising control group (C), and groups T1 and T2 receiving H-MSC treatment at doses of 3 x 106 and 1.5 x 106, respectively. To induce H-MSCs, MSCs were incubated in hypoxic conditions at 5% O2 and 37oC for 24 hours. Expression level of TGF-β was analyzed by enzyme-linked immunosorbent assay (ELISA) at 450 nm and adhesion formation was described macroscopically. The Kruskal-Wallis variance analysis was used to analyze significant differences among the groups.ResultsThe results of this study showed that H-MSCs in group T1 inhibited TGF-β expression significantly on day 8 (p<0.001) and day 14 (p<0.05). Moreover, there was almost no adhesion apparent following H-MSC administration in group T1. ConclusionsBased on this study, we conclude that H-MSCs may attenuate PA formation following inhibition of TGF-β expression in the PA rat model.
Suppression of transforming growth factor-β by mesenchymal stem-cells accelerates liver regeneration in liver fibrosis animal model Sa’dyah, Nur Anna C; Putra, Agung; Dirja, Bayu Tirta; Hidayah, Nurul; Yasmine Azzahara, Salma; Candra Satria Irawan, Risky
Universa Medicina Vol. 40 No. 1 (2021)
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2021.v40.29-35

Abstract

IntroductionLiver 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.MethodsIn 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. ResultsThe 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<0.05). The TGF-β suppression capability of T2 was optimal and more significant than that of T1.ConclusionMSCs can suppress TGF levels in liver fibrosis induced rats.
Hypoxia-preconditioned mesenchymal stem cells attenuate proinflammatory cytokines in collagen loss animal model Fristiani, Yeni; Putra, Agung; Sumarawati, Titiek; Setiawan, Eko; Ibrahim, Sugeng; Pramukarso, Dodik Tugasworo Pramukarso
Universa Medicina Vol. 44 No. 2 (2025)
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2025.v44.131-140

Abstract

Background Repeated ultraviolet-B (UVB) exposure induces significant collagen degradation, primarily through overproduction of reactive oxygen species, which subsequently drives an inflammatory cascade. Hypoxia-preconditioned mesenchymal stem cells (H-MSCs) constitute a promising therapeutic approach to counteract collagen loss by modulating inflammatory pathways. This study aimed to evaluate the potential of H-MSCs in regulating NF-κB p65 and IL-1β expression in a collagen loss rat model, highlighting their therapeutic efficacy. Methods Twenty-five healthy male Wistar rats were randomly assigned to five groups: K1 (healthy controls), K2 (collagen loss), K3 (collagen loss + hyaluronic acid), K4 (collagen loss + 2.5 × 10⁵ H-MSCs), and K5 (collagen loss + 5 × 10⁵ H-MSCs). Collagen loss was induced by UVB radiation (peak wavelength: 302 nm) for 2 weeks. mRNA expression of NF-κB p65 was quantified by qRT-PCR, while IL-1β levels were assessed using ELISA. The rats were maintained for 14 days before being sacrificed, to allow the H-MSCs to exert their therapeutic effects. Data analysis was by One-way ANOVA with Tukey’s post-hoc test. Results The administration of H-MSCs significantly reduced IL-1β levels in groups K4 (633.14±63.76 pg/mL) and K5 (520.80±123.82 pg/mL) compared to group K2 (931.93±205.80 pg/mL) (p<0.05), with group K5 showing the most substantial reduction. Moreover, H-MSC injection in groups K4 and K5 effectively reduced NF-κB p65 expression levels (1.13±0.50 a.u. and 0.72±0.22 a.u., respectively), compared to group K2 (2.47±0.50 a.u.) (p<0.05), with group K5 providing optimum inhibition. Conclusion This study demonstrated that H-MSCs effectively attenuate UVB-induced inflammation and modulate key inflammatory pathways.
Secretome hypoxia-mesenchymal stem cells decrease tumor necrosis factor-α and interleukin-18 in kidney of type 2 diabetes mellitus model rats Irawan, Risky Chandra Satria; Putra, Agung; Setyo, Trisnadi; Ghaisani, Shabrina Syifa; Hidayah, Nurul
Universa Medicina Vol. 42 No. 3 (2023)
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2023.v42.320-328

Abstract

Background Type 2 diabetes mellitus (T2DM) is a chronic disease that affects millions of people worldwide and associated with an increased risk of kidney damage caused by prolonged inflammation. Secretome hypoxia- mesenchymal stem cells (SH-MSCs) have been investigated as a potential therapy for kidney inflammation in T2DM, due to their immunomodulatory properties and ability to promote tissue repair. In this study, we investigated the effects of SH-MSCs on tumor necrosis α (TNF-á) and interleukin-18 (IL-18) in the kidney of the T2DM model rats. MethodsA post-test-only control group involving 24 male Wistar rats. The rats were treated with a high-fat diet (HFD) for 4 weeks and streptozotocin-nicotinamide with sucrose solution for 5 days to induce T2DM animal models. Rats were randomly divided into four groups: healthy, control, and groups treated with SH-MSCs T1 and T2, with doses of 250 µL and 500 µL, respectively. TNF-α and IL-18 gene expression was measured by real time polymerase chain reaction (RT-PCR). One Way ANOVA and post-hoc LSD tests were used to determine the significant difference against all groups based on their quantitative measurement. ResultsAdministration of the SH-MSCs at a dose of 500µL (T2) was able to significantly reduce TNF-α and IL-18 gene expression when compared to control (T2DM rat without treatment) (p<0.05), but not significantly when compared to healthy and SH-MSC at a dose of 250µL (T1) group (p>0.05). ConclusionThis study demonstrated that the SH-MSCs decreased the levels of proinflammatory cytokines TNF-α and IL-18 gene expression in the kidney of T2DM model rats.
Hypoxic mesenchymal stem cell-derived secretome and alkaline water synergistically reduce apoptosis and insulin resistance in type 2 diabetes mellitus rat model Mawarini, Melisa Septi; Setiawan, Eko; Putra, Agung
Universa Medicina Vol. 44 No. 3 (2025)
Publisher : Faculty of Medicine, Universitas Trisakti

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.18051/UnivMed.2025.v44.310-317

Abstract

BACKGROUNDType 2 Diabetes Mellitus (T2DM) is characterized by chronic inflammation and insulin resistance. These factors contribute to pancreatic β-cell apoptosis, reducing insulin production and impairing glucose homeostasis. This study aims to evaluate the protective effects of hypoxic mesenchymal stem cell-derived secretome (HMSCS) and alkaline water on inflammation, apoptosis, and insulin resistance in a T2DM rat model. METHODSAn experimental study was conducted involving 24 male Wistar T2DM model rats (aged 6-8 weeks, 200-250g). They were randomized into four groups: T2DM rats only as negative control (K-), T2DM rats with metformin as positive control (K+), HMSCS treatment (P1), and HMSCS plus alkaline water group (P2). Caspase-3 expression was measured to assess apoptosis levels using RT-PCR, while homeostatic model assessment for insulin resistance (HOMA-IR) was measured using ELISA. One way ANOVA followed by a post hoc LSD test were used to analyse the data. RESULTSThe P1 group (3.03 ± 1.26 a.u) and P2 group (2.93 ± 0.52 a.u.) had significantly lower caspase-3 expression compared to K- group (6.66 ± 2.76 a.u.) (p<0.05), but were not significantly different from K+ group (3.83 ± 1.61 a.u.) (p>0.05). Additionally, P2 group (6.76 ± 0.96) had a significantly lower HOMA-IR than K- group (18.92 ± 2.63) and K+ group (10.85 ± 1.39) (p<0.05), and similarly the P1 (7.71 ± 0.53) group also showed significant difference from K- and K+ groups (p<0.05). CONCLUSIONHigher doses of HMSCS and alkaline water are associated with reduced pancreatic β-cell apoptosis and improved insulin sensitivity, highlighting its potential as a novel therapeutic approach for T2DM.
Co-Authors Agus Widyatmoko, Agus Alif, Iffan Amalina, Nur D. Amalina, Nur Dina Amin, Mustafa M. Andavania, Sheila Jessica Andreas, Yana Antari, Arini Dewi Azizah Retno Kustiyah Cahyani, Dini Cahyani, Elvana Cahyono, Erwin Budi Candra Satria Irawan, Risky Catharina Suharti Chodidjah Chodidjah Chodijah , Chodijah Darlan, Dewi M. Daulay, Rini S. Delfitri Munir Dewi, Alisia Martha Dirja, Bayu T. Dirja, Bayu Tirta Djannah, Durrotul Edi Dharmana Eko Setiawan Eko Setiawan Erna Mutiara Evita Mayasari Fahreza, Rakha Fatmawati, Dian Fikriya Novita Sari Firman Alamsyah Fristiani, Yeni Ghaisani, Shabrina Syifa Ginting, Andi R. Hadi Sarosa Haitamy, Mohammad Nurrizki Handoyo, Frigi Eko Hariani, Nova Putri Hasanal, Ihdina Hanifa Hasannuri, Tarrayuana Rhamadia Heri Nugroho HS, Zakariya Husain, Sofian A. Hutabarat, Nenny Lynda Caroline Hutagalung, Ananta Ibrahim, Sugeng Ignatius Riwanto, Ignatius Intan, Yulice Soraya Nur Irawan Mangunatmadja Irawan, Risky Chandra Irawan, Risky Chandra Satria Isfandiari, Adelia Bayu Iskandar Japardi Jessika, Cleveria Khan, Ahmed Faheem Kuntardjo, Novalia Lusiana Lusiana Mardiana, Ana Maryanti Maryanti Mawarini, Melisa Septi Minidian Fasitasari Muchaeroni, Isa Anshori Muhar, Adi Muradi Noka, Isara Abda Nugraha, Dendi Krisna Nur Anna Chalimah Sadyah NURUL HIDAYAH Pasongka, Zenitalia Pramukarso, Dodik Tugasworo Pramukarso Prasetio, Ardi Prasetyowati Subchan, Prasetyowati Prawitasari, Salindri Purwaningsih, Hesti Rahardja, Carolina Kiwik Rarastoeti Pratiwi Rozi, Muhammad F. Rusda, Muhammad Sa’dyah, Nur Anna C Sari, Shintia Devi Arum Selamat Budijitno Setiawan , Eko Setyo Trisnadi Setyo, Trisnadi Shafia, Arina Sisca Silvana, Sisca Sitompul, Faya Nuralda Sri Priyantini Sri Priyantini Mulyani Sri Sofyani, Sri Subchan, Prastyowati Sulistami, Siska Marlina Sulistyo, Sona Sunarto, Hadi Sutrisman, Intan Permatasari Suwandi Ng Syamsunarno, Mas Rizky Syamsunarno, Mas Rizky A.A Taskworo, Dodik Taufiq R Nasihun, Taufiq R Titiek Sumarawati Tjipta, Arya Trisnasi, Setyo Utami, Wulan Dyah Yasmine Azzahara, Salma Yayun Siti Rochmah Yustianingsih, Vivi