Publications
24 results found
Kim YJ, Cho MJ, Yu WD, et al., 2022, Links of cytoskeletal integrity with disease and aging, Cells, Vol: 11, ISSN: 2073-4409
Aging is a complex feature and involves loss of multiple functions and nonreversible phenotypes. However, several studies suggest it is possible to protect against aging and promote rejuvenation. Aging is associated with many factors, such as telomere shortening, DNA damage, mitochondrial dysfunction, and loss of homeostasis. The integrity of the cytoskeleton is associated with several cellular functions, such as migration, proliferation, degeneration, and mitochondrial bioenergy production, and chronic disorders, including neuronal degeneration and premature aging. Cytoskeletal integrity is closely related with several functional activities of cells, such as aging, proliferation, degeneration, and mitochondrial bioenergy production. Therefore, regulation of cytoskeletal integrity may be useful to elicit antiaging effects and to treat degenerative diseases, such as dementia. The actin cytoskeleton is dynamic because its assembly and disassembly change depending on the cellular status. Aged cells exhibit loss of cytoskeletal stability and decline in functional activities linked to longevity. Several studies reported that improvement of cytoskeletal stability can recover functional activities. In particular, microtubule stabilizers can be used to treat dementia. Furthermore, studies of the quality of aged oocytes and embryos revealed a relationship between cytoskeletal integrity and mitochondrial activity. This review summarizes the links of cytoskeletal properties with aging and degenerative diseases and how cytoskeletal integrity can be modulated to elicit antiaging and therapeutic effects.
Thanh HP, Kim SY, Rudge C, et al., 2022, Made by cells for cells - extracellular vesicles as next-generation mainstream medicines, Journal of Cell Science, Vol: 135, Pages: 1-13, ISSN: 0021-9533
Current medicine has only taken us so far in reducing disease and tissue damage. Extracellular vesicles (EVs), which are membranous nanostructures produced naturally by cells, have been hailed as a next-generation medicine. EVs deliver various biomolecules, including proteins, lipids and nucleic acids, which can influence the behaviour of specific target cells. Since EVs not only mirror composition of their parent cells but also modify the recipient cells, they can be used in three key areas of medicine: regenerative medicine, disease detection and drug delivery. In this Review, we discuss the transformational and translational progress witnessed in EV-based medicine to date, focusing on two key elements: the mechanisms by which EVs aid tissue repair (for example, skin and bone tissue regeneration) and the potential of EVs to detect diseases at an early stage with high sensitivity and specificity (for example, detection of glioblastoma). Furthermore, we describe the progress and results of clinical trials of EVs and demonstrate the benefits of EVs when compared with traditional medicine, including cell therapy in regenerative medicine and solid biopsy in disease detection. Finally, we present the challenges, opportunities and regulatory framework confronting the clinical application of EV-based products.
Ferreira PM, Bayer S, Zhu D, et al., 2022, Extracellular Vesicles in Lung Diseases, EXTRACELLULAR VESICLES, Editors: Chrzanowski, Lim, Kim, Publisher: ROYAL SOC CHEMISTRY, Pages: 216-245, ISBN: 978-1-78801-894-4
Chrzanowski W, Lim CT, Kim SY, 2022, Extracellular Vesicles Applications to Regenerative Medicine, Therapeutics and Diagnostics <i>Preface</i>, EXTRACELLULAR VESICLES, Editors: Chrzanowski, Lim, Kim, Publisher: ROYAL SOC CHEMISTRY, Pages: V-VI, ISBN: 978-1-78801-894-4
Roisin M, Kim SY, Van der Plaat D, et al., 2021, LSC-2021-Investigating the role of vitamin A intake and retinoic acid signalling in lung homeostasis and repair-A multidisciplinary approach, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Kim SY, Mongey S, Wang P, et al., 2021, The Acid Injury and Repair (AIR) model: A new ex vivo tool to understand lung repair, Biomaterials, Vol: 267, ISSN: 0142-9612
Research into mechanisms underlying lung injury and subsequent repair responses is currently of paramount importance. There is a paucity of models that bridge the gap between in vitro and in vivo research. Such intermediate models are critical for researchers to decipher the mechanisms that drive repair and to test potential new treatments for lung repair and regeneration. Here we report the establishment of a new tool, the Acid Injury and Repair (AIR) model, that will facilitate studies of lung tissue repair. In this model, injury is applied to a restricted area of a precision-cut lung slice using hydrochloric acid, a clinically relevant driver. The surrounding area remains uninjured, thus mimicking the heterogeneous pattern of injury frequently observed in lung diseases. We show that in response to injury, the percentage of progenitor cells (pro surfactant protein C, proSP-C and TM4SF1 positive) significantly increases in the injured region. Whereas in the uninjured area, the percentage of proSP-C/TM4SF1 cells remains unchanged but proliferating cells (Ki67 positive) increase. These effects are modified in the presence of inhibitors of proliferation (Cytochalasin D) and Wnt secretion (C59) demonstrating that the AIR model is an important new tool for research into lung disease pathogenesis and potential regenerative medicine strategies.
Kim S, Mongey R, Griffiths M, et al., 2020, An ex vivo acid injury and repair (AIR) model using precision-cut lung slices to understand lung injury and repair, Current protocols in mouse biology, Vol: 10, Pages: e85-e85, ISSN: 2161-2617
Recent advances in cell culture models like air‒liquid interface culture and ex vivo models such as organoids have advanced studies of lung biology; however, gaps exist between these models and tools that represent the complexity of the three‐dimensional environment of the lung. Precision‐cut lung slices (PCLS) mimic the in vivo environment and bridge the gap between in vitro and in vivo models. We have established the acid injury and repair (AIR) model where a spatially restricted area of tissue is injured using drops of HCl combined with Pluronic gel. Injury and repair are assessed by immunofluorescence using robust markers, including Ki67 for cell proliferation and prosurfactant protein C for alveolar type 2/progenitor cells. Importantly, the AIR model enables the study of injury and repair in mouse lung tissue without the need for an initial in vivo injury, and the results are highly reproducible. Here, we present detailed protocols for the generation of PCLS and the AIR model. We also describe methods to analyze and quantify injury in AIR‐PCLS by immunostaining with established early repair markers and fluorescence imaging. This novel ex vivo model is a versatile tool for studying lung cell biology in acute lung injury and for semi‐high‐throughput screening of potential therapeutics. © 2020 Wiley Periodicals LLC.
Cheong SS, Akram K, Metellan C, et al., 2020, The planar polarity component Vangl2 is a key regulator of mechanosignaling, Frontiers in Cell and Developmental Biology, Vol: 8, ISSN: 2296-634X
VANGL2 is a component of the planar cell polarity (PCP) pathway, which regulates tissue polarity and patterning. The Vangl2Lp mutation causes lung branching defects due to dysfunctional actomyosin-driven morphogenesis. Since the actomyosin network regulates cell mechanics, we speculated that mechanosignaling could be impaired when VANGL2 is disrupted. Here, we used live-imaging of precision-cut lung slices (PCLS) from Vangl2Lp/+ mice to determine that alveologenesis is attenuated as a result of impaired epithelial cell migration. Vangl2Lp/+ tracheal epithelial cells (TECs) and alveolar epithelial cells (AECs) exhibited highly disrupted actomyosin networks and focal adhesions (FAs). Functional assessment of cellular forces confirmed impaired traction force generation in Vangl2Lp/+ TECs. YAP signaling in Vangl2Lp airway epithelium was reduced, consistent with a role for VANGL2 in mechanotransduction. Furthermore, activation of RhoA signaling restored actomyosin organization in Vangl2Lp/+, confirming RhoA as an effector of VANGL2. This study identifies a pivotal role for VANGL2 in mechanosignaling, which underlies the key role of the PCP pathway in tissue morphogenesis.
Chrzanowski W, Kim SY, McClements L, 2020, Can stem cells beat COVID-19: advancing stem cells and extracellular vesicles toward mainstream medicine for lung injuries associated with SARS-CoV-2 infections, Frontiers in Bioengineering and Biotechnology, Vol: 8, Pages: 1-8, ISSN: 2296-4185
A number of medicines are currently under investigation for the treatment of COVID-19 disease including anti-viral, anti-malarial, and anti-inflammatory agents. While these treatments can improve patient's recovery and survival, these therapeutic strategies do not lead to unequivocal restoration of the lung damage inflicted by this disease. Stem cell therapies and, more recently, their secreted extracellular vesicles (EVs), are emerging as new promising treatments, which could attenuate inflammation but also regenerate the lung damage caused by COVID-19. Stem cells exert their immunomodulatory, anti-oxidant, and reparative therapeutic effects likely through their EVs, and therefore, could be beneficial, alone or in combination with other therapeutic agents, in people with COVID-19. In this review article, we outline the mechanisms of cytokine storm and lung damage caused by SARS-CoV-2 virus leading to COVID-19 disease and how mesenchymal stem cells (MSCs) and their secreted EVs can be utilized to tackle this damage by harnessing their regenerative properties, which gives them potential enhanced clinical utility compared to other investigated pharmacological treatments. There are currently 17 clinical trials evaluating the therapeutic potential of MSCs for the treatment of COVID-19, the majority of which are administered intravenously with only one clinical trial testing MSC-derived exosomes via inhalation route. While we wait for the outcomes from these trials to be reported, here we emphasize opportunities and risks associated with these therapies, as well as delineate the major roadblocks to progressing these promising curative therapies toward mainstream treatment for COVID-19.
Kim S, Chrzanowski W, 2019, Stem cell delivery systems and devices - Spraying, Stem Cell-Based Therapy for Lung Disease, Editors: Burgess, Heijink, Publisher: Springer Nature, Pages: 241-253, ISBN: 9783030294038
Kim SY, Mongey R, Wang P, et al., 2019, LSC-2019-A novel ex-vivo approach to study lung injury and repair, European-Respiratory-Society (ERS) International Congress, Publisher: European Respiratory Society, ISSN: 0903-1936
Kim SY, Joglekar MV, Hardikar AA, et al., 2019, Placenta Stem/Stromal Cell-Derived Extracellular Vesicles for Potential Use in Lung Repair, PROTEOMICS, Vol: 19, ISSN: 1615-9853
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- Citations: 17
Kim SY, Phan TH, Limantoro C, et al., 2019, Isolation and Characterization of Extracellular Vesicles from Mesenchymal Stromal Cells, Progenitor Cells, Editors: Joglekar, Hardikar, Publisher: Springer, Pages: 15-23, ISBN: 978-1-4939-9631-5
Kim SY, Khanal D, Kalionis B, et al., 2019, High-fidelity probing of the structure and heterogeneity of extracellular vesicles by resonance-enhanced atomic force microscopy infrared spectroscopy, NATURE PROTOCOLS, Vol: 14, Pages: 576-593, ISSN: 1754-2189
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- Citations: 58
Kim SY, Khanal D, Tharkar P, et al., 2018, None of us is the same as all of us: resolving the heterogeneity of extracellular vesicles using single-vesicle, nanoscale characterization with resonance enhanced atomic force microscope infrared spectroscopy (AFM-IR), NANOSCALE HORIZONS, Vol: 3, Pages: 430-438, ISSN: 2055-6756
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- Citations: 36
Jaffar J, Yang S-H, Kim SY, et al., 2018, Greater cellular stiffness in fibroblasts from patients with idiopathic pulmonary fibrosis, AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 315, Pages: L59-L65, ISSN: 1040-0605
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- Citations: 34
Yang K, Leslie KG, Kim SY, et al., 2018, Tailoring the properties of a hypoxia-responsive 1,8-naphthalimide for imaging applications, Organic and Biomolecular Chemistry, Vol: 16, Pages: 619-624, ISSN: 1477-0520
Sensing hypoxia in tissues and cell models can provide insights into its role in disease states and cell development. Fluorescence imaging is a minimally-invasive method of visualising hypoxia in many biological systems. Here we present a series of improved bioreductive fluorescent sensors based on a nitro-naphthalimide structure, in which selectivity, photophysical properties, toxicity and cellular uptake are tuned through structural modifications. This new range of compounds provides improved probes for imaging and monitoring hypoxia, customised for a range of different applications. Studies in monolayers show the different reducing capabilities of hypoxia-resistant and non-resistant cell lines, and studies in tumour models show successful staining of the hypoxic region.
Reczynska K, Tharkar P, Kim SY, et al., 2018, Animal models of smoke inhalation injury and related acute and chronic lung diseases, Advanced Drug Delivery Reviews, Vol: 123, Pages: 107-134, ISSN: 0169-409X
Smoke inhalation injury leads to various acute and chronic lung diseases and thus is the dominant cause of fire-related fatalities. In a search for an effective treatment and validation of therapies different classes of animal models have been developed, which include both small and large animals. These models have advanced our understanding of the mechanism of smoke inhalation injury, enabling a better understanding of pathogenesis and pathophysiology and development of new therapies. However, none of the animal models fully mirrors human lungs and their pathologies. All animal models have their limitations in replicating complex clinical conditions associated with smoke inhalation injury in humans. Therefore, for a correct interpretation of the results and to avoid bias, a precise understanding of similarities and differences of lungs between different animal species and humans is critical. We have reviewed and presented comprehensive comparison of different animal models and their clinical relevance. We presented an overview of methods utilized to induce smoke inhalation injuries, airway micro-/macrostructure, advantages and disadvantages of the most commonly used small and large animal models.
Bjorge IM, Kim SY, Mano JF, et al., 2017, Extracellular vesicles, exosomes and shedding vesicles in regenerative medicine - a new paradigm for tissue repair, Biomaterials Science, Vol: 6, Pages: 60-78, ISSN: 2047-4830
Tissue regeneration by stem cells is driven by the paracrine activity of shedding vesicles and exosomes, which deliver specific cargoes to the recipient cells. Proteins, RNA, cytokines and subsequent gene expression, orchestrate the regeneration process by improving the microenvironment to promote cell survival, controlling inflammation, repairing injury and enhancing the healing process. The action of microRNA is widely accepted as an essential driver of the regenerative process through its impact on multiple downstream biological pathways, and its ability to regulate the host immune response. Here, we present an overview of the recent potential uses of exosomes for regenerative medicine and tissue engineering. We also highlight the differences in composition between shedding vesicles and exosomes that depend on the various types of stem cells from which they are derived. The conditions that affect the production of exosomes in different cell types are deliberated. This review also presents the current status of candidate exosomal microRNAs for potential therapeutic use in regenerative medicine, and in applications involving widely studied organs and tissues such as heart, lung, cartilage and bone.
Kim SY, Burgess JK, Wang Y, et al., 2016, Atomized human amniotic mesenchymal stromal cells for direct delivery to the airway for treatment of lung injury, Journal of Aerosol Medicine and Pulmonary Drug Delivery, Vol: 29, Pages: 514-524, ISSN: 0894-2684
Background: Current treatment regimens for inhalation injury are mainly supportive and rely on self-regeneration processes for recovery. Cell therapy with mesenchymal stromal cells (MSCs) is increasingly being investigated for the treatment of inhalation injury. Human amniotic MSCs (hAMSCs) were used in this study due to their potential use in inflammatory and fibrotic conditions of the lung. This study aimed at demonstrating that hAMSCs can be atomized with high viability, for the purpose of achieving a more uniform distribution of cells throughout the lung. Another aim of this study was to set ground for future application to healthy and diseased lungs by demonstrating that hAMSCs were able to survive after being sprayed onto substrates with different stiffness.Methods: Two methods of atomization were evaluated, and the LMA MAD780 device was selected for atomizing hAMSCs for optimized delivery. To mimic the stiffness of healthy and diseased lungs, gelatin gel (10% w/v) and tissue culture plastic were used as preliminary models. Poly-l-lysine (PLL) and collagen I coatings were used as substrates on which the hAMSCs were cultured after being sprayed.Results: The feasibility of atomizing hAMSCs was demonstrated with high cell viability (81 ± 3.1% and 79 ± 11.6% for cells sprayed onto plastic and gelatin, respectively, compared with 85 ± 4.8% for control/nonsprayed cells) that was unaffected by the different stiffness of substrates. The presence of the collagen I coating on which the sprayed cells were cultured yielded higher cell proliferation compared with both PLL and no coating. The morphology of sprayed cells was minimally compromised in the presence of the collagen I coating.Conclusions: This study demonstrated that hAMSCs are able to survive after being sprayed onto substrates with different stiffness, especially in the presence of collagen I. Further studies may advance the effectiveness of cell th
Kim SY, Naskar D, Kundu SC, et al., 2015, Formulation of biologically-inspired silk-based drug carriers for pulmonary delivery targeted for lung cancer, Scientific Reports, Vol: 5, Pages: 1-13, ISSN: 2045-2322
The benefits of using silk fibroin, a major protein in silk, are widely established in many biomedical applications including tissue regeneration, bioactive coating and in vitro tissue models. The properties of silk such as biocompatibility and controlled degradation are utilized in this study to formulate for the first time as carriers for pulmonary drug delivery. Silk fibroin particles are spray dried or spray-freeze-dried to enable the delivery to the airways via dry powder inhalers. The addition of excipients such as mannitol is optimized for both the stabilization of protein during the spray-freezing process as well as for efficient dispersion using an in vitro aerosolisation impactor. Cisplatin is incorporated into the silk-based formulations with or without cross-linking, which show different release profiles. The particles show high aerosolisation performance through the measurement of in vitro lung deposition, which is at the level of commercially available dry powder inhalers. The silk-based particles are shown to be cytocompatible with A549 human lung epithelial cell line. The cytotoxicity of cisplatin is demonstrated to be enhanced when delivered using the cross-linked silk-based particles. These novel inhalable silk-based drug carriers have the potential to be used as anti-cancer drug delivery systems targeted for the lungs.
Kim SY, Wong AHM, Abou Neel EA, et al., 2015, The future perspectives of natural materials for pulmonary drug delivery and lung tissue engineering, EXPERT OPINION ON DRUG DELIVERY, Vol: 12, Pages: 869-887, ISSN: 1742-5247
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- Citations: 12
Kim SY, Naskar D, Hibbs D, et al., 2014, TARGETED TREATMENT OF LUNG CANCER USING SILK-BASED DRUG CARRIERS, Publisher: WILEY-BLACKWELL, Pages: 34-35, ISSN: 1743-7555
Chrzanowski W, Kim SY, Abou Neel EA, 2013, Biomedical applications of clay, Australian Journal of Chemistry: an international journal for chemical science, Vol: 66, Pages: 1315-1322, ISSN: 0004-9425
Traditional applications of clay mineral mainly revolved around cosmetics and industrial products, but their scope of application is continuously expanding into pharmaceutics including drug delivery and tissue engineering. The interest in clays amongst the scientific community has increased dramatically in recent years due to its composition and structure which can be easily modified to serve different purposes. Largely due to structural flexibility and its small particle size, clay nanostructure can be modified to tune rheological and mechanical properties, and can entrap moisture to suit a particular application. Additionally, interest in the synthesis of polymer-clay nanocomposites in tissue engineering is growing as it is cheap, easily available, and environmentally-friendly. The structure of clay allows the interclaysion of different biomolecules between the clay layers. These biomolecules can be released in a controlled manner which can be utilised in drug delivery and cosmetic applications.
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