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Arai, Yoshie,Park, Sunghyun,Choi, Bogyu,Ko, Kyoung-Won,Choi, Won Chul,Lee, Joong-Myung,Han, Dong-Wook,Park, Hun-Kuk,Han, Inbo,Lee, Jong Hun,Lee, Soo-Hong MDPI 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.6
<P>Human adipose-derived stem cells (hASCs) have a capacity to undergo adipogenic, chondrogenic, and osteogenic differentiation. Recently, hASCs were applied to various fields including cell therapy for tissue regeneration. However, it is hard to predict the direction of differentiation of hASCs in real-time. Matrix metalloproteinases (MMPs) are one family of proteolytic enzymes that plays a pivotal role in regulating the biology of stem cells. MMPs secreted by hASCs are expected to show different expression patterns depending on the differentiation state of hASCs because biological functions exhibit different patterns during the differentiation of stem cells. Here, we investigated proteolytic enzyme activity, especially MMP-2 activity, in hASCs during their differentiation. The activities of proteolytic enzymes and MMP-2 were higher during chondrogenic differentiation than during adipogenic and osteogenic differentiation. During chondrogenic differentiation, mRNA expression of MMP-2 and the level of the active form of MMP-2 were increased, which also correlated with Col II. It is concluded that proteolytic enzyme activity and the level of the active form of MMP-2 were increased during chondrogenic differentiation, which was accelerated in the presence of Col II protein. According to our findings, MMP-2 could be a candidate maker for real-time detection of chondrogenic differentiation of hASCs.</P>
Arai Yoshie,Lee Soo-Hong 한국조직공학과 재생의학회 2023 조직공학과 재생의학 Vol.20 No.3
BACKGROUND: Matrix metalloproteinases (MMPs) are proteins involved in the repair and remodeling the extracellular matrix (ECM). MMP13 is essential for bone development and healing through the remodeling of type I collagen (COL1), the main component of the ECM in bone tissue. Mesenchymal stem cells (MSCs)-based cell therapy has been considered a promising approach for bone regeneration because of their osteogenic properties. However, the approaches using MSC to completely regenerate bone tissue have been limited. To overcome the limitation, genetic engineering of MSC could be a strategy for promoting regeneration efficacy. METHODS: We performed in vitro and in vivo experiments using MMP13-overexpressing MSCs in the presence of COL1. To examine MMP13-overexpressing MSCs in vivo, we prepared a fibrin/COL1-based hydrogel to encapsulate MSCs and subcutaneously implanted gel-encapsulated MSCs in nude mice. We found that the osteogenic marker genes, ALP and RUNX2, were upregulated in MMP13-overexpressing MSCs through p38 phosphorylation. In addition, MMP13 overexpression in MSCs stimulated the expression of integrin a3, which is upstream receptor of p38, and substantially increased osteogenic differentiation potential of MSCs. Bone tissue formation in MMP13-overexpressing MSCs was significantly higher than that in control MSCs. Taken together, our findings demonstrate that MMP13 is not only an essential factor for bone development and bone healing but also has a pivotal role in promoting osteogenic differentiation of MSCs to induce bone formation. CONCLUSION: MSCs Genetically engineered to overexpress MMP13, which have a powerful potential to differentiate into the osteogenic cells, might be beneficial in bone disease therapy.
Surface-Modified Gold Nanorods for Specific Cell Targeting
Chan-Ung Wang,Yoshie Arai,Insun Kim,장원희,이승현,Jason H. Hafner,정은희,Deokho Jung,권영은 한국물리학회 2012 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.60 No.10
Gold nanoparticles (GNPs) have unique properties that make them highly attractive materials for developing functional reagents for various biomedical applications including photothermal therapy, targeted drug delivery, and molecular imaging. For <I>in vivo</I> applications, GNPs need to be prepared with very little or negligible cytotoxicitiy. Most GNPs are, however, prepared using growth-directing surfactants, such as cetyl trimethylammonium bromide (CTAB), which are known to have considerable cytotoxicity. In this paper, we describe an approach to remove CTAB to a non-toxic concentration. We optimized the conditions for surface modification with methoxypolyethylene glycol thiol (mPEG) which replaced CTAB and formed a protective layer on the surface of GNPs. The cytotoxicity of pristine and surface-modified gold nanorods (GNRs) was measured in human cell lines derived from hepatic carcinoma, embryonic kidney, umbilical vein endothelia, and thyroid papillary carcinoma. Cytotoxicity assays revealed that treating cells with GNRs do not significantly affect cell viability except for thyroid papillary carcinoma cells. Thyroid cancer cells are more susceptible to residual CTAB, so that CTAB has to be further removed by dialysis in order to use GNRs for thyroid cell targeting. PEGylated GNRs are further modified to present monoclonal antibodies that recognize a specific surface marker, Na-I symporter, for thyroid cells. Antibody-conjugated GNRs specifically targeted human thyroid cells <I>in vitro</I>.
Bose, Rajendran JC,Arai, Yoshie,Ahn, Jong Chan,Park, Hansoo,Lee, Soo-Hong Dove Medical Press 2015 INTERNATIONAL JOURNAL OF NANOMEDICINE Vol.10 No.-
<P>Nanoparticles have been widely used for nonviral gene delivery. Recently, cationic hybrid nanoparticles consisting of two different materials were suggested as a promising delivery vehicle. In this study, nanospheres with a poly(<SMALL>D</SMALL>,<SMALL>L</SMALL>-lactic-<I>co</I>-glycolic acid) (PLGA) core and cationic lipid shell were prepared, and the effect of cationic lipid concentrations on the properties of lipid polymer hybrid nanocarriers investigated. Lipid–polymer hybrid nanospheres (LPHNSs) were fabricated by the emulsion-solvent evaporation method using different concentrations of cationic lipids and characterized for size, surface charge, stability, plasmid DNA-binding capacity, cytotoxicity, and transfection efficiency. All LPHNSs had narrow size distribution with positive surface charges (ζ-potential 52–60 mV), and showed excellent plasmid DNA-binding capacity. In vitro cytotoxicity measurements with HEK293T, HeLa, HaCaT, and HepG2 cells also showed that LPHNSs exhibited less cytotoxicity than conventional transfection agents, such as Lipofectamine and polyethyleneimine–PLGA. As cationic lipid concentrations increased, the particle size of LPHNSs decreased while their ζ-potential increased. In addition, the in vitro transfection efficiency of LPHNSs increased as lipid concentration increased.</P>
Drug repositioning of tauroursodeoxycholic acid for bone tissue regeneration
이수홍,차병현,김병주,( Arai Yoshie ),김병수,한인보 한국공업화학회 2016 한국공업화학회 연구논문 초록집 Vol.2016 No.0
Bone tissue engineering from bone morphogenetic protein (BMP) and stem cells has been developed with various strategies for enhancement of therapeutic effect. Our recent study found that chemical chaperone tauroursodeoxycholic acid (TUDCA) significantly reduces adipogenesis of mesenchymal stem cells (MSCs). In present study, we examine whether TUDCA as an alternative drug of BMP is able to activate bone tissue regeneration by reducing adipose tissue. It was observed that TUDCA treatment was able to promote in vivo bone tissue regeneration at calvarial defect model and spinal fusion model. In addition, TUDCA treatment significantly decreases apoptosis and inflammatory response in vivo as well as in vitro. The results indicate that TUDCA plays a critical role in not only enhancing in vivo bone regeneration also reducing adipose tissue at implantation site, therefore, would be a potential alternative drug for bone tissue regeneration in pharmacologic and therapeutic applications.
Nityanand Prakash,Jiseong Kim,Jieun Jeon,김시연,Yoshie Arai,Alvin Bacero Bello,박한수,이수홍 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00
The use of mesenchymal stem cells (MSCs) for clinical purposes has skyrocketed in the past decade. Their multilineage differentiation potentials and immunomodulatory properties have facilitated the discovery of therapies for various illnesses. MSCs can be isolated from infant and adult tissue sources, which means they are easily available. However, this raises concerns because of the heterogeneity among the various MSC sources, which limits their effective use. Variabilities arise from donor- and tissue-specific differences, such as age, sex, and tissue source. Moreover, adult-sourced MSCs have limited proliferation potentials, which hinders their long-term therapeutic efficacy. These limitations of adult MSCs have prompted researchers to develop a new method for generating MSCs. Pluripotent stem cells (PSCs), such as embryonic stem cells and induced PSCs (iPSCs), can differentiate into various types of cells. Herein, a thorough review of the characteristics, functions, and clinical importance of MSCs is presented. The existing sources of MSCs, including adult- and infant-based sources, are compared. The most recent techniques for deriving MSCs from iPSCs, with a focus on biomaterial-assisted methods in both two- and threedimensional culture systems, are listed and elaborated. Finally, several opportunities to develop improved methods for efficiently producing MSCs with the aim of advancing their various clinical applications are described.