The Impact of Adhesion Molecules on the In Vitro Culture and Differentiation of Stem Cells

Abdal Dayem, Ahmed,Lee, Soobin,Y. Choi, Hye,Cho, Ssang-Goo WILEY 2018 BIOTECHNOLOGY JOURNAL Vol.13 No.2

Biologically synthesized silver nanoparticles induce neuronal differentiation of SH-SY5Y cells via modulation of reactive oxygen species, phosphatases, and kinase signaling pathways.

Dayem, Ahmed Abdal,Kim, BongWoo,Gurunathan, Sangiliyandi,Choi, Hye Yeon,Yang, Gwangmo,Saha, Subbroto Kumar,Han, Dawoon,Han, Jihae,Kim, Kyeongseok,Kim, Jin-Hoi,Cho, Ssang-Goo Wiley 2014 BIOTECHNOLOGY JOURNAL Vol.9 No.7

<P>Nano-scale materials are noted for unique properties, distinct from those of their bulk material equivalents. In this study, we prepared spherical silver nanoparticles (AgNPs) with an average size of about 30 nm and tested their potency to induce neuronal differentiation of SH-SY5Y cells. Human neuroblastoma SH-SY5Y cells are considered an ideal in vitro model for studying neurogenesis, as they can be maintained in an undifferentiated state or be induced to differentiate into neuron-like phenotypes in vitro by several differentiation-inducing agents. Treatment of SH-SY5Y cells by biologically synthesized AgNPs led to cell morphological changes and significant increase in neurite length and enhanced the expression of neuronal differentiation markers such as Map-2, β-tubulin III, synaptophysin, neurogenin-1, Gap-43, and Drd-2. Furthermore, we observed an increase in generation of intracellular reactive oxygen species (ROS), activation of several kinases such as ERK and AKT, and downregulation of expression of dual-specificity phosphatases (DUSPs) in AgNPs-exposed SH-SY5Y cells. Our results suggest that AgNPs modulate the intracellular signaling pathways, leading to neuronal differentiation, and could be applied as promising nanomaterials for stem cell research and therapy.</P>

Recent advances in organoid culture for insulin production and diabetes therapy: methods and challenges

( Ahmed Abdal Dayem ),( Soo Bin Lee ),( Kyeongseok Kim ),( Kyung Min Lim ),( Tak-il Jeon ),( Ssang-goo Cho ) 생화학분자생물학회(구 한국생화학분자생물학회) 2019 BMB Reports Vol.52 No.5

Breakthroughs in stem cell technology have contributed to disease modeling and drug screening via organoid technology. Organoid are defined as three-dimensional cellular aggregations derived from adult tissues or stem cells. They recapitulate the intricate pattern and functionality of the original tissue. Insulin is secreted mainly by the pancreatic β cells. Large-scale production of insulin-secreting β cells is crucial for diabetes therapy. Here, we provide a brief overview of organoids and focus on recent advances in protocols for the generation of pancreatic islet organoids from pancreatic tissue or pluripotent stem cells for insulin secretion. The feasibility and limitations of organoid cultures derived from stem cells for insulin production will be described. As the pancreas and gut share the same embryological origin and produce insulin, we will also discuss the possible application of gut organoids for diabetes therapy. Better understanding of the challenges associated with the current protocols for organoid culture facilitates development of scalable organoid cultures for applications in biomedicine. [BMB Reports 2019; 52(5): 295-303]

Methods for Enhanced Proliferation and Differentiation of Human Mesenchymal Stem Cells

Ahmed Abdal Dayem,Ssang-Goo Cho 한국수정란이식학회 2018 한국수정란이식학회 학술대회 Vol.2018 No.11

Stem cells have special properties, such as self-renewal, proliferation, and the multilineage differentiation. Generally, stem cells are categorized into embryonic stem cells (ESCs), adult stem cells (ASCs), and induced pluripotent stem cells (iPSCs). Mesenchymal stem cells (MSCs) are a type of ASCs with a multipotent property. MSCs are easily isolated from various tissues and organs in the human body and can differentiation into multiple lineages, such as bone, cartilage, fat, and muscles. Compared to ESCs and iPSCs, MSCs possess less proliferation and differentiation capacities, therefore, a much scientific concern is concerned toward promoting the proliferation and the differentiation potency of MSCs. There are various methods to achieve this goal such as the treatment of various types of small molecules or culturing on specific peptides. Producing of high-quality MSCs with enhanced proliferation and differentiation capacities will definitely be a useful tool for stem cell-mediated tissue regeneration and the further clinical application.

New therapeutic approach with extracellular vesicles from stem cells for interstitial cystitis/bladder pain syndrome

( Ahmed Abdal Dayem ),( Kwonwoo Song ),( Soobin Lee ),( Aram Kim ),( Ssang-goo Cho ) 생화학분자생물학회 2022 BMB Reports Vol.55 No.5

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a debilitating chronic disorder characterized by suprapubic pain and urinary symptoms such as urgency, nocturia, and frequency. The prevalence of IC/BPS is increasing as diagnostic criteria become more comprehensive. Conventional pharmacotherapy against IC/BPS has shown suboptimal effects, and consequently, patients with end-stage IC/BPS are subjected to surgery. The novel treatment strategies should have two main functions, anti-inflammatory action and the regeneration of glycosaminoglycan and urothelium layers. Stem cell therapy has been shown to have dual functions. Mesenchymal stem cells (MSCs) are a promising therapeutic option for IC/BPS, but they come with several shortcomings, such as immune activation and tumorigenicity. MSC-derived extracellular vesicles (MSC-EVs) hold numerous therapeutic cargos and are thus a viable cell-free therapeutic option. In this review, we provide a brief overview of IC/BPS pathophysiology and limitations of the MSC-based therapies. Then we provide a detailed explanation and discussion of therapeutic applications of EVs in IC/BPS as well as the possible mechanisms. We believe our review will give an insight into the strengths and drawbacks of EV-mediated IC/BPS therapy and will provide a basis for further development. [BMB Reports 2022; 55(5): 205-212]

Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

Kawser Hossain, Mohammed,Abdal Dayem, Ahmed,Han, Jihae,Kumar Saha, Subbroto,Yang, Gwang-Mo,Choi, Hye Yeon,Cho, Ssang-Goo MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.2

<P>Diabetes mellitus (DM) is a widespread metabolic disease with a progressive incidence of morbidity and mortality worldwide. Despite extensive research, treatment options for diabetic patients remains limited. Although significant challenges remain, induced pluripotent stem cells (iPSCs) have the capacity to differentiate into any cell type, including insulin-secreting pancreatic β cells, highlighting its potential as a treatment option for DM. Several iPSC lines have recently been derived from both diabetic and healthy donors. Using different reprogramming techniques, iPSCs were differentiated into insulin-secreting pancreatic βcells. Furthermore, diabetes patient-derived iPSCs (DiPSCs) are increasingly being used as a platform to perform cell-based drug screening in order to develop DiPSC-based cell therapies against DM. Toxicity and teratogenicity assays based on iPSC-derived cells can also provide additional information on safety before advancing drugs to clinical trials. In this review, we summarize recent advances in the development of techniques for differentiation of iPSCs or DiPSCs into insulin-secreting pancreatic β cells, their applications in drug screening, and their role in complementing and replacing animal testing in clinical use. Advances in iPSC technologies will provide new knowledge needed to develop patient-specific iPSC-based diabetic therapies.</P>

Hydrodynamic shear stress promotes epithelial-mesenchymal transition by downregulating ERK and GSK3β activities

Choi, Hye Yeon,Yang, Gwang-Mo,Dayem, Ahmed Abdal,Saha, Subbroto Kumar,Kim, Kyeongseok,Yoo, Youngbum,Hong, Kwonho,Kim, Jin-Hoi,Yee, Cassian,Lee, Kyung-Mi,Cho, Ssang-Goo BioMed Central 2019 Breast cancer research Vol.21 No.-

<P><B>Background</B></P><P>Epithelial-mesenchymal transition (EMT) occurs in the tumor microenvironment and presents an important mechanism of tumor cell intravasation, stemness acquisition, and metastasis. During metastasis, tumor cells enter the circulation to gain access to distant tissues, but how this fluid microenvironment influences cancer cell biology is poorly understood.</P><P><B>Methods and results</B></P><P>Here, we present both in vivo and in vitro evidence that EMT-like transition also occurs in circulating tumor cells (CTCs) as a result of hydrodynamic shear stress (+SS), which promotes conversion of CD24<SUP>middle</SUP>/CD44<SUP>high</SUP>/CD133<SUP>middle</SUP>/CXCR4<SUP>low</SUP>/ALDH1<SUP>low</SUP> primary patient epithelial tumor cells into specific high sphere-forming CD24<SUP>low</SUP>/CD44<SUP>low</SUP>/CD133<SUP>high</SUP>/CXCR4<SUP>high</SUP>/ALDH1<SUP>high</SUP> cancer stem-like cells (CSLCs) or tumor-initiating cells (TICs) with elevated tumor progression and metastasis capacity in vitro and in vivo. We demonstrate that conversion of CSLCs/TICs from epithelial tumor cells via +SS is dependent on reactive oxygen species (ROS)/nitric oxide (NO) generation, and suppression of extracellular signal-related kinase (ERK)/glycogen synthase kinase (GSK)3β, a mechanism similar to that operating in embryonic stem cells to prevent their differentiation while promoting self-renewal.</P><P><B>Conclusion</B></P><P>Fluid shear stress experienced during systemic circulation of human breast tumor cells can lead to specific acquisition of mesenchymal stem cell (MSC)-like potential that promotes EMT, mesenchymal-epithelial transition, and metastasis to distant organs. Our data revealed that biomechanical forces appeared to be important microenvironmental factors that not only drive hematopoietic development but also lead to acquisition of CSLCs/TIC potential in cancer metastasis. Our data highlight that +SS is a critical factor that promotes the conversion of CTCs into distinct TICs in blood circulation by endowing plasticity to these cells and by maintaining their self-renewal signaling pathways.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (10.1186/s13058-018-1071-2) contains supplementary material, which is available to authorized users.</P>

The effects of human milk proteins on the proliferation of normal, cancer and cancer stem like cells

Kang, Nam Mi,Cho, Ssang-Goo,Dayem, Ahmed Abdal,Lee, Joohyun,Bae, Seong Phil,Hahn, Won-Ho,Lee, Jeong-Sang The Korean Society of Analytical Sciences 2018 분석과학 Vol.31 No.6

Human breast milk (HBM) provides neonates with indispensable nutrition. The present study evaluated the anti-cancer activity of diluted and pasteurized early HBM (< 6 weeks' lactation) on human breast cancer cell lines. The cell lines MCF7 and MDA-MB231 were exposed to 1 % HBM from the 1st, 3rd, and 6th weeks of lactation and exhibited reduced proliferation rates. As controls, breast cell lines (293T and MCF-10A), breast cancer cell lines (MCF-7 and MDA-MB-231), and $CD133^{hi}CXCR4^{hi}ALDH1^{hi}$ patient-derived human cancer stem-like cells (KU-CSLCs) were treated with prominent milk proteins ${\beta}$-casein, ${\kappa}$-casein, and lactoferrin at varying doses (10, 50, and $100{\mu}g$) for 24 or 48 hrs. The impact of these proteins on cell proliferation was investigated. Breast cancer cell lines treated with ${\kappa}$-casein and lactoferrin exhibited significantly reduced viability, in both a dose- and time-dependent manner. Interestingly, ${\kappa}$-casein selectively impacted only cancer (but not normal breast) cell lines, particularly the more malignant cell line. However, ${\beta}$-casein-exposed human breast cancer cell lines exhibited a significantly higher proliferation rate. Thus, ${\kappa}$-casein and lactoferrin appear to exert selective anti-cancer activities. Further studies are warranted to determine the mechanisms underlying ${\kappa}$-casein- and lactoferrin-mediated cancer cell-selective cytotoxic effects.

Green synthesis of anisotropic silver nanoparticles and its potential cytotoxicity in human breast cancer cells (MCF-7)

Sangiliyandi Gurunathan,김진회,한재웅,Ahmed Abdal Dayem,Vasuki Eppakayala,박정현,조쌍구,이경진 한국공업화학회 2013 Journal of Industrial and Engineering Chemistry Vol.19 No.5

We described a green, cost effective and rapid method for synthesizing anisotropic AgNPs using a novel bacterium called Escherichia fergusoni. Furthermore, synthesized AgNPs were characterized by various analytical techniques. The present study demonstrates the efficiency of biologically synthesized AgNPs as a cytotoxic agent against MCF-7 cells and also this study investigates possible molecular mechanisms underlying the cytotoxic effects of AgNPs. AgNPs showed dose dependent cytotoxicity against MCF-7cells through activation of the lactate dehydrogenase (LDH), reactive oxygen species (ROS) generation and eventually leading to induction of apoptosis which was further confirmed through resulting nuclear fragmentation.

Antiviral Activity of 3,4'-Dihydroxyflavone on Influenza A Virus

Mohammed Kawser Hossain,최혜연,황재선,Ahmed Abdal Dayem,김정현,김영봉,부하령,조쌍구 한국미생물학회 2014 The journal of microbiology Vol.52 No.6

Influenza virus infection causes thousands of deaths and millionsof hospitalizations worldwide every year and the emergenceof resistance to anti-influenza drugs has promptedscientists to seek new natural antiviral materials. In this study,we screened 13 different flavonoids from various flavonoidgroups to identify the most potent antiviral flavonoid againsthuman influenza A/PR/8/34 (H1N1). The 3-hydroxyl groupflavonoids, including 3,2'-dihydroxyflavone (3,2'-DHF) and3,4 -dihydroxyflavone (3,4'-DHF), showed potent anti-influenzaactivity. They inhibited viral neuraminidase activityand viral adsorption onto cells. To confirm the anti-influenzaactivity of these flavonoids, we used an in vivo mousemodel. In mice infected with human influenza, oral administrationof 3,4'-DHF significantly decreased virus titers andpathological changes in the lung and reduced body weightloss and death. Our data suggest that 3-hydroxyl group flavonoids,particularly 3,4'-DHF, have potent antiviral activityagainst human influenza A/PR/8/34 (H1N1) in vitro and invivo. Further clinical studies are needed to investigate thetherapeutic and prophylactic potential of the 3-hydroxylgroup flavonoids in treating influenza pandemics.