CHA Bio and Diostech Co.

Seoul, South Korea

CHA Bio and Diostech Co.

Seoul, South Korea
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Kim J.,CHA Bio and Diostech Co. | Jeon Y.-J.,Chonbuk National University | Kim H.E.,CHA Medical University | Shin J.M.,CHA Bio and Diostech Co. | And 3 more authors.
Biomaterials | Year: 2013

Vasculopathy due to ischemia in damaged tissues is a major cause of morbidity and mortality. To treat these conditions, endothelial progenitor cells (EPCs) from various sources, such as umbilical cord or peripheral blood, have been the focus of the regenerative medicine field due to their proliferative and vasculogenic activities. However, the fundamental, molecular-level differences between EPCs obtained from different cellular sources have rarely been studied. In this study, we established endothelial progenitor cells derived from cord blood- and peripheral blood (CB- and PB-EPCs) and investigated their fundamental differences at the cellular and molecular levels through a combination of stem cell biology techniques and proteomic analysis. Our results suggest that specifically up-regulated factors such as STMIN 1, CFL 1, PARK 7, NME 1, GLO 1, HSP 27 and PRDX 2 in CB-EPCs as key elements that could be functionally active in ischemic regions. We also discussed functional behaviors important for inducing and maintaining long-lasting blood vessels under ischemic conditions. As a result, CB-EPCs retained a higher anti-oxidant and migration ability than PB-EPCs in vitro. Furthermore, CB-EPCs retained a higher therapeutic efficacy than PB-EPCs in a hindlimb ischemic disease model. The up-regulated expression pattern of STMIN 1, CFL 1, PARK 7, NME 1, GLO 1, HSP 27 and PRDX 2 was confirmed under several conditions in vitro and in vivo, indicating that the up-regulation of these molecules in CB-EPCs may be critical to the mechanism of healing in ischemic conditions and that CB-EPCs may be more appropriate for inducing neo-vessels. Thus, these results may aid in predetermining which cell sources will be of value for cell-based therapies of pathological conditions and identify several candidate molecules that may be involved in the therapeutic mechanism for ischemia. © 2012 Elsevier Ltd.

Lee M.J.,CHA Medical University | Kim J.,CHA Bio and Diostech Co. | Lee K.I.,CHA Medical University | Shin J.M.,CHA Bio and Diostech Co. | And 3 more authors.
Cytotherapy | Year: 2011

Background aims. Stem cells have been shown to have a therapeutic effect in several ischemic animal models, including hindlimb ischemia and chronic wound. We examined the wound-healing effect of secretory factors released by human embryonic stem cell (hESC)-derived endothelial precursor cells (EPC) in cutaneous excisional wound models. Methods. hESC-EPC were sorted by CD133/KDR, and endothelial characteristics were confirmed by reverse transcription (RT)-polymerase chain reaction (PCR), Matrigel assay and ac-LDL uptake. Conditioned medium (CM) of hESC-EPC was prepared, and concentrated hESC-EPC CM was applied in a mouse excisional wound model. Results. hESC-EPC CM accelerated wound healing and increased the tensile strength of wounds after topical treatment and subcutaneous injection. In addition, hESC-EPC CM treatment caused more rapid re-formation of granulation tissue and re-epithelialization of wounds compared with control vehicle medium and CB-EPC CM-treated wounds. In vitro, hESC-EPC CM significantly improved the proliferation and migration of dermal fibroblasts and epidermal keratinocytes. hESC-EPC CM also increased the extracellular matrix synthesis of fibroblasts. Analysis of hESC-EPC CM with a multiplex cytokine array system indicated that hESC-EPC secreted distinctively different cytokines and chemokines, such as epidermal growth factor (EGF), fibroblast growth factor (bFGF), fractalkine, granulocytemacrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6, IL-8, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor (VEGF), which are well known to be important in normal angiogenesis and wound healing. Conclusions. This study has demonstrated the wound-healing effect of hESC-EPC CM and characterized the spectrum of cytokines released by hESC-EPC that are functionally involved in the wound-healing process. These results suggest that secretory factors released from stem cells could be an important mediator of stem cell therapy in ischemic tissue diseases. © 2011 Informa Healthcare.

Park J.S.,CHA Medical University | Shim M.-S.,CHA Medical University | Shim S.H.,CHA Medical University | Yang H.N.,CHA Medical University | And 5 more authors.
Biomaterials | Year: 2011

In this study, several types of hMSCs, derived from bone marrow, adipose tissue, or amniotic fluid, were encapsulated in a fibrin hydrogel mixed with TGF-β3 and then evaluated for their capacity for differentiation in vitro and in vivo. For determination of stem cell differentiation, RT-PCR, real time quantitative PCR (qPCR), histology, and immunohistochemical assays were used for analysis of chondrogenesis. Using these analysis methods, several of the cultured hMSCS were found to highly express genes and proteins specific to cartilage forming tissues. Additionally, similar trends in expression were found in tissue recovered from nude mice transplanted with several types of hMSCs encapsulated in a fibrin hydrogel containing TGF-β3. The results of both in vitro and in vivo analyses showed that cultured or transplanted hMSCs mixed with TGF-β3 in a fibrin hydrogel differentiated into chondrocytes, suggesting that these cells would be suitable for reconstruction of hyaline articular cartilage. © 2011 Elsevier Ltd.

Moon S.-H.,CHA Bio and Diostech Co. | Kim J.-S.,CHA Medical University | Park S.-J.,CHA Medical University | Lim J.-J.,CHA Medical University | And 4 more authors.
Stem Cell Research | Year: 2011

The therapeutic potential of human embryonic stem cells (hESCs) has long been appreciated, and the recent FDA approval of hESC derivatives for cell-based therapy encourages the clinical application of hESCs. Here, using CHA3-hESCs with normal and abnormal karyotypes, we report the importance of maintaining normal chromosomes during in vitro culture and the differentiation of hESCs for minimization of posttransplantation complications. We found that undifferentiated CHA3-hESCs with trisomy chromosome 12 undergo abnormal cell division with multiple spindles in comparison to the bipolar cell division of the karyotypically normal CHA3-hESCs. Transplanted karyotypically abnormal CHA3-hESC derivatives formed a tumor-like tissue 6. weeks after transplantation in two out of seven mice tested. Our results demonstrate that the preservation of normal chromosomes is indispensable for maintaining the true properties of hESCs in vitro and abolishing adverse effects posttransplantation. Thus, the development of optimized techniques for stabilizing the chromosome state during in vitro hESC culture is a prerequisite for the therapeutic application of hESCs. © 2010 Elsevier B.V.

Kim J.,CHA Bio and Diostech Co. | Shin J.M.,CHA Bio and Diostech Co. | Jeon Y.J.,Chonbuk National University | Chung H.M.,CHA Bio and Diostech Co. | And 2 more authors.
PLoS ONE | Year: 2012

Mesenchymal stem cells (MSCs) are one of the most attractive therapeutic resources in clinical application owing to their multipotent capability, which means that cells can differentiate into various mesenchymal tissues such as bone, cartilage, fat, tendon, muscle and marrow stroma. Depending on the cellular source, MSCs exhibit different application potentials according to their different in vivo functions, despite similar phenotypic and cytological characteristics. To understand the different molecular conditions that govern the different application or differentiation potential of each MSC according to cellular source, we generated a proteome reference map of MSCs obtained from bone marrow (BM), umbilical cord blood (CB) and peripheral blood (PB). We identified approximately 30 differentially regulated (or expressed) proteins. Most up-regulated proteins show a cytoskeletal and antioxidant or detoxification role according to their functional involvement. Additionally, these proteins are involved in the increase of cell viability, engraftment and migration in pathological conditions in vivo. In summary, we examined differentially expressed key regulatory factors of MSCs obtained from several cellular sources, demonstrated their differentially expressed proteome profiles and discussed their functional role in specific pathological conditions. With respect to the field of cell therapy, it may be particularly crucial to determine the most suitable cell sources according to target disease. © 2012 Kim et al.

Park S.G.,CHA Medical University | Kim J.H.,CHA Medical University | Kim J.H.,CHA Bio and Diostech Co. | Xia Y.,University of Houston | Sung J.-H.,CHA Medical University
Expert Opinion on Therapeutic Targets | Year: 2011

Introduction: Reactive oxygen species (ROS) participate in cellular apoptosis and are involved in pathophysiological etiology of degenerative diseases. However, recent studies suggest that ROS at low levels may play a pivotal role as second messengers and activate normal cellular processes. Intracellular ROS increase the proliferation, migration, and regenerative potential of adipose-derived stem cells (ASCs). In contrast, manipulations that diminish intracellular ROS levels interfere with normal ASC function. ROS generation therefore acts like a double-edged sword. Areas covered: This review discusses the following research questions: i) Do ROS stimulate or suppress ASCs? ii) How are ROS generated from ASCs? iii) Which function(s) is/are regulated by intracellular ROS generation? In addition, the antioxidant/ antiapoptotic effect of ASCs is briefly introduced. Expert opinion: Whether ROS is harmful or beneficial is primarily a question of dosage. Low or moderate ROS generation increases the proliferation, migration and regenerative potential of ASCs. Therefore, it is beneficial to expose ASCs to moderate oxidative stress during manipulation. The addition of a ROS donor in culture can reduce the cost for the expansion of ASCs and a ROS preconditioning can enhance the regenerative potential of ASCs. © 2011 Informa UK, Ltd.

Lee H.-J.,Cha Bio and Diostech Co. | Cha K.E.,CHA Medical University | Hwang S.-G.,Korea University | Kim J.K.,Korea University | Kim G.J.,CHA Medical University
Journal of Cellular Biochemistry | Year: 2011

Stem cells have unique properties such as self-renewal, plasticity to generate various cell types, and availability of cells of human origin. The characteristics are attentive in the toxicity screening against chemical toxicants. Placenta-derived stem cells (PDSCs) have been spotlighted as a new cell source in stem cell research recently because they are characterized by their capacity to differentiate into multilineages. However, the use of PDSCs as an in vitro screening model for potential drug candidates has not yet been studied. Here, we analyzed the potentials for bone-marrow-derived mesenchymal stem (BM-MSCs), which is a representative adult stem cells and PDSCs as an in vitro hepatotoxicity screening system, using well-known hepatotoxicants. BM-MSCs and PDSCs were analyzed to the potential for hepatogenic differentiation and were cultured with different concentrations of hepatotoxicants for time courses. The viability and ATP-binding cassette (ABC) transporters were measured by the MTT assay and RT-PCR, respectively. The sensitivities of PDSCs to hepatotoxicants are more sensitive than those of BM-MSCs. The viability (IC 50) to in PDSCs was less than that of BM-MSCs after 48 and 72 h (P<0.05) of CCl4 exposure. The toxicities of CCl4 were decreased by fourfold in hepatogenic differentiation inducing PDSCs compared to the undifferentiated cells. The alteration of ABCGs was observed in PDSCs during differentiation. These findings suggest that the naïve PDSCs expressing ABCGs can be used as a source for in vitro screening system as well as the expression patterns of ABCG1 and ABCG2 might be involved in the sensitivity of PDSCs to hepatotoxicants. © 2010 Wiley-Liss, Inc.

Song S.-Y.,CHA Medical University | Chung H.-M.,CHA Stem Cell Institute | Chung H.-M.,CHA Medical University | Chung H.-M.,CHA Bio and Diostech Co. | And 3 more authors.
Expert Opinion on Biological Therapy | Year: 2010

Importance of the field: Several lines of evidence suggest that VEGF is a key regulator of the paracrine effects of adipose-derived stem cells (ASCs), but the mechanism of action remains to be identified. Areas covered in this review: This brief review discusses the following research questions: i) Does VEGF increase the proliferation/migration and differentiation of ASCs?; ii) Does VEGF mediate the paracrine effects of ASCs?; and iii) How is VEGF synthesized, and which factors regulate VEGF secretion? What the reader will gain: External stimuli such as hypoxia may activate receptor tyrosine kinases in the membrane of ASCs, which, in turn, phosphorylate extracellular signal regulated kinase (ERK) and members of the Akt signaling pathway, stabilizing hypoxia inducible factor 1α (HIF-1α) that are primary regulators of VEGF expression. Secreted VEGF directly stimulates ASCs via VEGF receptors in an autocrine manner and regenerates damaged neighboring cells in a paracrine manner. Take home message: Most studies of stem cell regeneration have focused on differentiation of ASCs and their building block function; however, the paracrine effects of ASCs should also be the focus of attention. © 2010 Informa UK, Ltd.

Moon S.-H.,Konkuk University | Ju J.,Korea University | Park S.-J.,Konkuk University | Bae D.,CHA Bio and Diostech Co. | And 2 more authors.
Biomaterials | Year: 2014

Human embryonic stem cells (hESCs) are generally induced to differentiate by forming spherical structures termed embryoid bodies (EBs) in the presence of soluble growth factors. hEBs are generated by suspending small clumps of hESC colonies; however, the resulting hEBs are heterogeneous because this method lacks the ability to control the number of cells in individual EBs. This heterogeneity affects factors that influence differentiation such as cell-cell contact and the diffusion of soluble factors, and consequently, the differentiation capacity of each EB varies. Here, we fabricated size-tunable concave microwells to control the physical environment, thereby regulating the size of EBs formed from single hESCs. Defined numbers of single hESCs were forced to aggregate and generate uniformly sized EBs with high fidelity, and the size of the EBs was controlled using concave microwells of different diameters. Differentiation patterns in H9- and CHA15-hESCs were affected by EB size in both the absence and presence of growth factors. By screening EB size in the presence of various BMP4 concentrations, a two-fold increase in endothelial cell differentiation was achieved. Because each hESC line has unique characteristics, the findings of this study demonstrate that concave microwells could be used to screen different EB sizes and growth factor concentrations to optimize differentiation for each hESC line. © 2014 Elsevier Ltd.

Kim M.J.,Konkuk University | Choi H.W.,Konkuk University | Jang H.J.,Konkuk University | Chung H.M.,CHA Bio and Diostech Co Ltd. | And 3 more authors.
Journal of Cell Science | Year: 2013

Induced pluripotent stem cells (iPSCs), generated from somatic cells by overexpression of transcription factors Oct4, Sox2, Klf4 and c- Myc have the same characteristics as pluripotent embryonic stem cells (ESCs). iPSCs reprogrammed from differentiated cells undergo epigenetic modification during reprogramming, and ultimately acquire a similar epigenetic state to that of ESCs. In this study, these epigenetic changes were observed in reprogramming of uniparental parthenogenetic somatic cells. The parthenogenetic pattern of imprinted genes changes during the generation of parthenogenetic maternal iPSCs (miPSCs), a process referred to as pluripotent reprogramming. We determined whether altered imprinted genes are maintained or revert to the parthenogenetic state when the reprogrammed cells are redifferentiated into specialized cell types. To address this question, we redifferentiated miPSCs into neural stem cells (miPS-NSCs) and compared them with biparental female NSCs (fNSCs) and parthenogenetic NSCs (pNSCs). We found that pluripotent reprogramming of parthenogenetic somatic cells could reset parthenogenetic DNA methylation patterns in imprinted genes, and that alterations in DNA methylation were maintained even after miPSCs were redifferentiated into miPS-NSCs. Notably, maternally methylated imprinted genes (Peg1, Peg3, Igf2r, Snrpn and Ndn), whose differentially methylated regions were fully methylated in pNSCs, were demethylated and their expression levels were found to be close to the levels in normal biparental fNSCs after reprogramming and redifferentiation. Our findings suggest that pluripotent reprogramming of parthenogenetic somatic cells followed by redifferentiation leads to changes in DNA methylation of imprinted genes and the reestablishment of gene expression levels to those of normal biparental cells. © 2013. Published by The Company of Biologists Ltd.

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