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Spatial learning and memory of young and aging rats following injection with human Wharton’s jelly‐mesenchymal stem cells Berry Juliandi; Wildan Mubarok; Dian Anggraini; Arief Boediono; Mawar Subangkit; Indra Bachtiar; Harry Murti; Kelvin Yaprianto; Boenjamin Setiawan
Indonesian Journal of Biotechnology Vol 26, No 2 (2021)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijbiotech.64734

Abstract

Human Wharton’s jelly‐mesenchymal stem cells (hWJ‐MSC) are an emerging potential source of stem cells derived from the umbilical cord. Previous studies have shown their potential as treatment for traumatic brain injury and Parkinson’s disease. However, no study has yet investigated the effect of hWJ‐MSC injections in countering spatial learning and memory impairment in aging rats. The effect of hWJ‐MSC injection on young rats is also unknown. The objective of this research was to analyze the effect of an hWJ‐MSC injection on spatial learning, memory, density of putative neural progenitor cells (pNPC), and neuronal apoptosis in the dentate gyrus (DG) of young and aging rats. Injection of hWJ‐MSC did not change spatial learning and memory in young rats until two months post‐injection. This might be due to retained pNPC density and neuronal apoptosis in the DG of young rats after injection of hWJ‐MSC. In contrast, injection of hWJ‐MSC promoted both spatial learning and memory in aging rats, a finding that might be attributable to the increased pNPC density and attenuated neuronal apoptosis in DG of aging rats during the two months post‐injection. Our study suggests that a single injection of hWJ‐MSC might be sufficient to promote improvement in long‐term learning and memory in aging rats.
Penyuntikan Human Wharton’s Jelly Mesenchymal Stem Cells terhadap Perbaikan Fungsi Testis pada Tikus Tua Fisiologis (HUMAN WHARTON’S JELLY MESENCHYMAL STEM CELLS INJECTION AMELIORATE TESTICULAR FUNCTION ON PHYSIOLOGICAL AGING MALE RATS) Alif Iman Fitrianto; Adkhilni Utami; Wining Astini; Adisti Dwijayanti; Frans Dhyanagiri Suyatna; Kelvin Yaprianto; Indra Bachtiar; I Ketut Mudite Adnyane; Arief Boediono
Jurnal Veteriner Vol 19 No 3 (2018)
Publisher : Faculty of Veterinary Medicine, Udayana University and Published in collaboration with the Indonesia Veterinarian Association

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (182.764 KB)

Abstract

The most common therapy on men who suffered fertility decline due to aging was called “T Therapy”, but that’s therapy has long-term risks of sexual dysfunction, metabolic syndrome, prostate, and cardiovascular system. Stem cells are an alternative therapy can be used for ameliorate testicular fuction because of their ability to differentiate into various cell types. The aim of this study was to evaluate the injection of hWJ-MSC in physiologic aging male rats on testicular function. This study was used 3 young male rats (8-12 weeks) and 6 physiological aging male rats (22-24 months) which divided into 3 groups, (i) the young rats, (ii) physiological aging male rats, and (iii) physiological aging male rats that injected with hWJ-MSCs. The young rat group did not give any treatment, physiological aging male rats received NaCl (0.9%) 0.4 mL, and the treatment group received 1x106 cells/kg BW of hWJ-MSCs. The observations were performed on the macroscopical and histological analysis. The result indicates that the younger group had the lowest body weight (154.6 g) and the percentage of the testis weight on the body weight was highest (2.2%) compared to the other groups (P>0.05). The physiological aging rats group had the smallest tubule (9726.9 ìm2) with a largest interstitial area (1117.1 ìm2) compared the other groups (P>0.05). After injection of hWJ-MSC, the tubule area became wider followed by narrowing of the interstitial area (P>0.05). The difference in the body weights is due to the different age of the rat. Improvement of tubule area and interstitial area due to the ability of hWJ-MSCs to improve spermatogenic cells within the tubule. Injection of hWJ-MSCs has been shown to increase fertility in aging rats.
Perpanjangan Usia Tikus Tua Setelah Xenotransplantasi Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) Elpita Tarigan; Adisti Dwijayanti; Frans Dhyanagiri Suyatna; Indra Bachtiar; Sandy Qlintang; I Ketut Mudite Adnyane; Arief Boediono
Jurnal Veteriner Vol 21 No 4 (2020)
Publisher : Faculty of Veterinary Medicine, Udayana University and Published in collaboration with the Indonesia Veterinarian Association

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (218.261 KB) | DOI: 10.19087/jveteriner.2020.21.4.539

Abstract

Currently, mesenchymal stem cells (MSCs) for implementing regenerative medicine in aging become interest in medical research science, especially in degerative disease and other aging problems. This research was aimed to determine the effectiveness of hUC-MSCs on inhibiting the aging process through the lifetime of the rat and the effect of intravenous administration of hUC-MSCs in phisiologycally aging female rat on the blood analysis. This study was used 40 aged female rats with 29-30 months of age divided into four groups with 10 rats each. The control rat group was given physiological NaCl (0.9%) 0.5 mL, and the treated rat group was given hUC-MSCs 1x107 cells/kg body weight in 0.5 mL NaCl 0.9%, wasinjected intravenously in caudo lateralis tail vein with stratified frequency; one time injection (SC1), three times injections (SC3) and five times injections (SC5). Perifer blood was collected from retro-ortbital sinus vein 30 days before and after injection of hUC-MSCs for hematology and blood chemistry analysis. Based on the results were obtained, it indicated that hUC-MSCs increased the survival of aging rat werein treatment group, life span of rats was extended up to 40 months compared to the average life of control rat aged up to 34±2 months. The injection of hUC-MSCs 1x107 cells/kg of body weight with one, three andfive times injection were affected to blood profiles and blood chemistry with correlation were low. The conclusions are hUC-MSCs extend the lifespan of aging rat and were affect the blood in general but in normal range of aging rat, affect in ALT and creatinin as tissue repair and tolerated by aging rat.
Follicular Development of Aged Rats Ovarian Injected Human Umbilical Cord Mesenchymal Stem Cells Resti Rahma Dianti; Alif Iman Fitrianto; Adkhilni Utami; Wining Astini; Adisti Dwijayanti; Frans Dhyanagiri Suyatna; Kelvin Yaprianto; Indra Bachtiar; Aryani Sismin Satyaningtijas; Adi Winarto; Arief Boediono
Jurnal Riset Veteriner Indonesia (Journal of The Indonesian Veterinary Research) VOLUME 4 No. 1, JANUARY 2020
Publisher : Hasanuddin University

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20956/jrvi.v4i1.6889

Abstract

Female reproductive system showing the fastest signs of aging. The ovarian aging characterized by a decrease in follicular development. Stem cells are undifferentiated cells and can form a variety of different cells as the foundation of tissues and organs. Previous studies reported that Bone Marrow Mesenchymal Stem Cells (BM-MSCs) transplantation can restore follicular development in damaged ovarian rats. This study aimed to analyze the number of follicular development in aged rats and to analyze the capability of human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) to improving follicular development in aged rats. This study used 3 mature rats (4 months old), and 9 nine aged rats (22-24 months old), Spraque Dawley (SD) strain. They were divided into four groups. The first and the second group was mature rats and aged rats without injection. The third and the fourth group was aged rats injected hUC-MSCs dose 106 cells/kgBW and hUC-MSCs dose 107 cells/kgBW. The injection carried out 4 times at 3-month intervals. The parameters observed were follicular development and homing image of hUC-MSCs in ovarian tissue. The results showed that the number of follicular developments in aged rats 22-24 months decreased significantly compared to mature rats 4 months old. Injection of hUC-MSCs at dose 106 cells/kgBW and 107 cells/kgBW did not increase follicular development in aged rats. hUC-MSCs did not found in ovarian tissue. It could be concluded that aged rats 22-24 months old no longer productive indicated from the number of follicular developments and corpus luteum decreased. The injection of hUC-MSCs intravenously did not indicate an improvement of follicular development in aged rats 22-24 months old.
Induction of Matrix Metalloproteinases in Chondrocytes by Interleukin IL-1β as an Osteoarthritis Model Ervi Afifah; Tjandrawati Mozef; Ferry Sandra; Seila Arumwardana; Dwi Davidson Rihibiha; Hayatun Nufus; Rizal Rizal; Annisa Amalia; Indra Bachtiar; Harry Murti; Wahyu Widowati
Journal of Mathematical and Fundamental Sciences Vol. 51 No. 2 (2019)
Publisher : Institute for Research and Community Services (LPPM) ITB

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.5614/j.math.fund.sci.2019.51.2.1

Abstract

Osteoarthritis (OA) is a chronic disease of the joints and bones due to trauma or other joint-related diseases (secondary). Synovial inflammation commonly causes disturbance in joint homeostasis, which is associated with OA. Enzymes such as aggrecanase and metalloproteinase generate cartilage damage, mediated by tumor necrosis factor (TNF-α) and interleukin (IL)-1. Pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, are responsible for regulation of the extracellular matrix, cartilage degradation, and apoptosis of chondrocytes. This study aimed to observe the cell viability and expression level of matrix metalloproteinases (MMP-1 and MMP-3) and tissue inhibitor metalloproteinases (TIMP-1 and TIMP-2) in human chondrocyte cells (CHON-002) induced by IL-1β. CHON-002 was induced with IL-1β (0.1, 1 and 10 ng/mL) as an OA model. The viability of the cells was measured with a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxyme-thoxyphenyl)-2-(4-sulfophenyl)-2H-tetra zolium (MTS) assay, while expression of MMP-1, MMP-3, TIMP-1, and TIMP-2, was evaluated by RT-PCR. The viability of IL-1β-induced CHON-002 (CHON-002- IL-1β) cells at day 1 and 5 showed that treatment with up to 10 ng/mL of IL-1β was not toxic. Expression of TIMP-1 and TIMP-2 in CHON-002-IL-1β was lower compared to control, while that of MMP-1 and MMP-3 was higher compared to control. These results indicate that CHON-002 treated with 10 ng/mL IL-1β has expression patterns consistent with chondrocyte damage, so the CHON-002-IL-1β system may serve as a model for MMP induction in OA.
Effects of Conditioned Medium of Co-Culture IL-2 Induced NK Cells and Human Wharton’s Jelly Mesenchymal Stem Cells (hWJMSCs) on Apoptotic Gene Expression in a Breast Cancer Cell Line (MCF-7) Wahyu Widowati; Diana Krisanti Jasaputra; Philips Onggowidjaja; Sutiman Bambang Sumitro; Mochammad Aris Widodo; Ervi Afifah; Dwi Davidson Rihibiha; Rizal Rizal; Annisa Amalia; Hanna Sari Widya Kusuma; Harry Murti; Indra Bachtiar
Journal of Mathematical and Fundamental Sciences Vol. 51 No. 3 (2019)
Publisher : Institute for Research and Community Services (LPPM) ITB

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.5614/j.math.fund.sci.2019.51.3.1

Abstract

Breast cancer (BC) is the most prevalent type of cancer among women and one of the major causes of cancer mortality in women. Metastasis in breast cancer (BC) occurs due to immunosurveillance deficiency, including impairment of natural killer (NK) cell maturation. Conditioned medium (CM) from human Wharton's jelly mesenchymal stem cells (hWJMSC-CM) is known to possess anticancer activity. The CM of co-culture of human recombinant IL-2 treated NK cells and hWJMSCs is expected to boost anticancer activity toward BC cells which can be analyzed from the effect of CM towards secretion of effector molecules and expression of BC cell apoptosis-related genes, and cytotoxic granules in human recombinant IL-2 treated NK (IL-2 NK) and hWJMSCs (IL-2 hWJMSCs). TNF-α, IFN-γ, perforin, granzyme were measured by ELISA, while the inhibition of cell proliferation was measured by MTS assay and BC cell apoptosis by flow cytometry and apoptotic gene expression by RTPCR. CM from co-cultured hWJMSCs and IL-2 NK cells inhibited NK and BC cell proliferation, increased expression of Bax and p53 and decreased the number of Bcl-2 in BC cells. In conclusion, CM of co-culture IL-2 treated NK cells and hWJMSCs induce apoptosis in BC cells as indicated by increased Bax and p53 expression and decreased Bcl-2 expression. 
Edible Bird’s Nest Extract Reduced Expression of Senescence Markers in Bone Marrow Mesenchymal Stem Cells Lina Elfita; Ietje Wientarsih; Dondin Sajuthi; Indra Bachtiar; Huda Shalahudin Darusman
Jurnal Sains Farmasi & Klinis Vol 8, No 1 (2021): J Sains Farm Klin 8(1), April 2021
Publisher : Fakultas Farmasi Universitas Andalas

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (1568.937 KB) | DOI: 10.25077/jsfk.8.1.19-26.2021

Abstract

Edible bird’s nest (EBN) is often consumed as a health food due to its suggested health benefits, including anti-aging effects, however the mechanism is still unknown. This study investigated the effect of EBN extract using long term expansion bone marrow-derived mesenchymal stem cells (BMMSCs) as an aging model. Passage 5 (P5) and passage 8 (P8) BMMSCs were treated with EBN extract, and their proliferation, senescence-associated β-galactosidase (SA-β-Gal) activity, and expression of p16INK4a were analyzed. Treatment of BMMSCs with EBN extract decreased population doubling time (PDT) in P5 but not in P8 BMMSCs. In P5 BMMSCs, 200 ppm EBN extract increased BMMSCs proliferation, with PDT reduced by 27.6%. However, 200 ppm EBN extracts did not affect P8 BMMSCs proliferation, although it increased BMMSCs viability. Treatment of P5 and P8 BMMSCs with 200 ppm EBN extract decreased SA-β-Gal activity by 54.8% and 47.1% of the control, respectively (P<0.05). Levels of p16INK4a expression were 5.4-fold lower in P5 BMMSCs treated with 200 ppm EBN extract compared to control (P<0.05). Similarly, treatment of P8 BMMSCs with 200 ppm EBN extract reduced p16INK4a mRNA level by 7.9-fold compared to the control (P<0.05). In order to investigate the pathway of EBN extract inhibition, we further analyzed IL-6 and NF-κB1 expression. Treatment of P5 and P8 BMMSCs with 200 ppm EBN extract reduced IL-6 mRNA levels by 7.9-fold and 2.1-fold of control, respectively (P<0.05). We found that 200 ppm EBN extract reduced NF-κB1 mRNA level approximately 2.4-fold both in P5 and P8 BMMSCs (P<0.05). Thus, EBN extract reduces markers of senescence, indicated by decreased SA-β-Gal activity and p16INK4a mRNA level, and this correlated with reduced messenger RNA levels of the pro-inflammatory factor IL-6 and the transcription factor NF-κB1.
Co-Authors A.S. Satyaningtijas Adi Winarto Adisti Dwijayanti Adkhilni Utami Adkhilni Utami Alif Iman Fitrianto Alif Iman Fitrianto Annisa Amalia Annisa Amalia Arief Boediono Berry Juliandi Boenjamin Setiawan Dian Anggraini Diana Krisanti Jasaputra Dondin Sajuthi Dwi Davidson Rihibiha Dwi Davidson Rihibiha Elpita Tarigan Ervi Afifah Ervi Afifah Ferry Sandra Frans Dhyanagiri Suyatna Frans Dhyanagiri Suyatna Frans Dhyanagiri Suyatna Hanna Sari Widya Kusuma Harry Murti Harry Murti Harry Murti Hayatun Nufus Huda Shalahudin Darusman IETJE WIENTARSIH Kelvin Yaprianto Kelvin Yaprianto Kelvin Yaprianto Ketut Adnyane Mudite Lina Elfita Mochammad Aris Widodo Philips Onggowidjaja Resti Rahma Dianti Rizal Rizal Rizal Rizal Sandy Qlintang Seila Arumwardana Subangkit, Mawar Sutiman Bambang Sumitro Tjandrawati Mozef Wahyu Widowati Wahyu Widowati Wildan Mubarok Wining Astini Wining Astini