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Formulation of secretome derived from mesenchymal stem cells for inflammatory skin diseases
Seo Yoojin,Nguyen Tiep Tien,오수정,정지헌,Kim Hyung-Sik 한국약제학회 2023 Journal of Pharmaceutical Investigation Vol.53 No.2
Background Growing evidence has demonstrated that the administration of mesenchymal stem cells (MSCs) in various inflammatory skin diseases caused by autoimmune or allergic reactions can be served as promising therapeutics owing to their immunomodulatory effect as well as tissue regenerative capacity. Area covered In this review, we summarize the therapeutic application of MSCs and their secretome targeting inflammatory skin diseases and current secretome engineering strategies for the clinical translation of cell-free therapeutics. Expert opinion Considering that direct application of MSCs often fails to reproduce stable therapeutic outcomes, partially due to harsh in vivo microenvironment leading to insufficient survival of injected cells, the concept of cell-free approaches utilizing MSC-derived paracrine factors including secretome and exosome has emerged to overcome present issues. Furthermore, various bioengineering techniques with biocompatible materials can be applied to modulate naïve secretome to improve their delivery efficiency and bioavailability in vivo.
Decellularized heart ECM hydrogel using supercritical carbon dioxide for improved angiogenesis
Seo, Yoojin,Jung, Youngmee,Kim, Soo Hyun Elsevier Science B.V. Amsterdam 2018 ACTA BIOMATERIALIA Vol. No.
<P><B>Abstract</B></P> <P>Initial angiogenesis within the first 3 days is critical for healing ischemic diseases such as myocardial infarction. Recently, decellularized extracellular matrix (dECM) has been reported to provide tissue-derived ECM components and can be used as a scaffold for cell delivery for angiogenesis in tissue engineering. Decellularization by various detergents such as sodium dodecyl sulfate (SDS) and triton X-100 can remove the cell nuclei in tissue organs. However, this leads to ECM structure denaturation, decreased presence of various ECM proteins and cytokines, and loss of mechanical properties. To overcome these limitations, in this study, we developed a supercritical carbon dioxide and ethanol co-solvent (scCO<SUB>2</SUB>-EtOH) decellularization method, which is a detergent-free system that prevents ECM structure disruption and retains various angiogenic proteins in the heart dECM, and tested on rat heart tissues. The heart tissue was placed into the scCO<SUB>2</SUB> reactor and decellularized at 37 °C and 350 bar. After scCO<SUB>2</SUB>-EtOH treatment, the effects were evaluated by DNA, collagen, and glycosaminoglycan (GAG) quantification and hematoxylin and eosin and immunofluorescence staining to determine the absence of nucleic acids and preservation of heart ECM components. Similar to the native group, the scCO<SUB>2</SUB>-EtOH group contained more ECM components such as collagen, GAGs, collagen I, laminin, and fibronectin and angiogenic factors including vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor and others in comparison to the detergent group. In addition, to estimate angiogenesis of the dECM hydrogels, the neutralized dECM solution was injected in a rat subcutaneous layer (n = 6 in each group: collagen, scCO<SUB>2</SUB>-EOH, and detergent group), after which the solution naturally formed gelation in the subcutaneous layer. After 3 days, the gels were harvested and estimated by immunofluorescence staining and the ImageJ program for angiogenesis analysis. Consequently, blood vessel formation and density of vWF and α-SMA in the scCO<SUB>2</SUB>-EtOH group were significantly greater than that in the collagen group. Here we suggest that heart-derived decellularized extracellular matrix (dECM) with scCO<SUB>2</SUB>-EtOH treatment is a highly promising angiogenic material for healing in ischemic disease.</P> <P><B>Statement of Significance</B></P> <P>Supercritical carbon dioxide (scCO<SUB>2</SUB>) in a supercritical phase has low viscosity and high diffusivity between gas and liquid properties and is known to be affordable, non-toxic, and eco-friendly. Therefore, scCO<SUB>2</SUB> extraction technology has been extensively used in commercial and industrial fields. Recently, decellularized extracellular matrix (dECM) was applied to tissue engineering and regenerative medicine as a scaffold, therapeutic material, and bio-ink for 3D printing. Moreover, the general decellularization method using detergents has limitations including eliminating tissue-derived ECM components and disrupting their structures after decellularization. To overcome these limitations, heart tissues were treated with scCO<SUB>2</SUB>-EtOH for decellularization, resulting in preserving of tissue due to the various ECM and angiogenic factors derived. In addition, initiation of angiogenesis was highly induced even after 3 days of injection.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>
Stem Cell-Derived Extracellular Vesicles as Immunomodulatory Therapeutics
Seo, Yoojin,Kim, Hyung-Sik,Hong, In-Sun Hindawi 2019 Stem cells international Vol.2019 No.-
<P>Mesenchymal stem cells (MSCs) have been reported to possess regulatory functions on immune cells which make them alternative therapeutics for the treatment of inflammatory and autoimmune diseases. The interaction between MSCs and immune cells through paracrine factors might be crucial for these immunomodulatory effects of MSCs. Extracellular vesicles (EVs) are defined as bilayer membrane structures including exosomes and microvesicles which contain bioactive paracrine molecules affecting the characteristics of target cells. Recently, several studies have revealed that EVs derived from MSCs (MSC-EVs) can reproduce similar therapeutic impacts of parent MSCs; MSC-EVs could regulate proliferation, maturation, polarization, and migration of various immune effector cells and modulate the immune microenvironment depending on the context by delivering inflammatory cytokines, transcription factors, and microRNAs. Therefore, MSC-EVs can be applied as novel and promising tools for the treatment of immune-related disorders to overcome the limitations of conventional cell therapy regarding efficacy and toxicity issues. In this review, we will discuss current insights regarding the major outcomes in the evaluation of MSC-EV function against inflammatory disease models, as well as immune cells.</P>
Current Strategies to Enhance Adipose Stem Cell Function: An Update
Seo, Yoojin,Shin, Tae-Hoon,Kim, Hyung-Sik MDPI AG 2019 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.20 No.15
<P>Mesenchymal stem cells (MSCs) emerged as a promising therapeutic tool targeting a variety of inflammatory disorders due to their multiple remarkable properties, such as superior immunomodulatory function and tissue-regenerative capacity. Although bone marrow (BM) is a dominant source for adult MSCs, increasing evidence suggests that adipose tissue-derived stem cells (ASCs), which can be easily obtained at a relatively high yield, have potent therapeutic advantages comparable with BM-MSCs. Despite its outstanding benefits in pre-clinical settings, the practical efficacy of ASCs remains controversial since clinical trials with ASC application often resulted in unsatisfactory outcomes. To overcome this challenge, scientists established several strategies to generate highly functional ASCs beyond the naïve cells, including (1) pre-conditioning of ASCs with various stimulants such as inflammatory agents, (2) genetic manipulation of ASCs and (3) modification of culture conditions with three-dimensional (3D) aggregate formation and hypoxic culture. Also, exosomes and other extracellular vesicles secreted from ASCs can be applied directly to recapitulate the beneficial performance of ASCs. This review summarizes the current strategies to improve the therapeutic features of ASCs for successful clinical implementation.</P>