IGF-1 Genome-Edited Human MSCs Exhibit Robust Anti-Arthritogenicity in Collagen-Induced Arthritis.

Stem cell therapy stands out as a promising avenue for addressing arthritis treatment. However, its therapeutic efficacy requires further enhancement. In this study, we investigated the anti-arthritogenic potential of human amniotic mesenchymal stem cells (AMM) overexpressing insulin-like growth factor 1 (IGF-1) in a collagen-induced mouse model. The IGF-1 gene was introduced into the genome of AMM through transcription activator-like effector nucleases (TALENs). We assessed the in vitro immunomodulatory properties and in vivo anti-arthritogenic effects of IGF-1-overexpressing AMM (AMM/I). Co-culture of AMM/I with interleukin (IL)-1ß-treated synovial fibroblasts significantly suppressed NF-kB levels. Transplantation of AMM/I into mice with collagen-induced arthritis (CIA) led to significant attenuation of CIA progression. Furthermore, AMM/I administration resulted in the expansion of regulatory T-cell populations and suppression of T-helper-17 cell activation in CIA mice. In addition, AMM/I transplantation led to an increase in proteoglycan expression within cartilage and reduced infiltration by inflammatory cells and also levels of pro-inflammatory factors including cyclooxygenase-2 (COX-2), IL-1ß, NF-kB, and tumor necrosis factor (TNF)-α. In conclusion, our findings suggest that IGF-1 gene-edited human AMM represent a novel alternative therapeutic strategy for the treatment of arthritis.

Synergistic Therapeutic Potential of Dual 3D Mesenchymal Stem Cell Therapy in an Ischemic Hind Limb Mouse Model.

Three-dimensional (3D) culture systems have been widely used to promote the viability and metabolic activity of mesenchymal stem cells (MSCs). The aim of this study was to explore the synergistic benefits of using dual 3D MSC culture systems to promote vascular regeneration and enhance therapeutic potential. We used various experimental assays, including dual 3D cultures of human adipose MSCs (hASCs), quantitative reverse transcription polymerase chain reaction (qRT-PCR), in vitro cell migration, Matrigel tube network formation, Matrigel plug assay, therapeutic assays using an ischemic hind limb mouse model, and immunohistochemical analysis. Our qRT-PCR results revealed that fibroblast growth factor 2 (FGF-2), granulocyte chemotactic protein-2 (GCP-2), and vascular endothelial growth factor-A (VEGF-A) were highly upregulated in conventional 3D-cultured hASCs (ASC-3D) than in two-dimensional (2D)-cultured hASCs. Hepatocyte growth factor (HGF), insulin-like growth factor-1 (IGF-1), and stromal-cell-derived factor-1 (SDF-1) showed higher expression levels in cytokine-cocktail-based, 3D-cultured hASCs (ASC-3Dc). A conditioned medium (CM) mixture of dual 3D ASCs (D-3D; ASC-3D + ASC-3Dc) resulted in higher migration and Matrigel tube formation than the CM of single 3D ASCs (S-3D; ASC-3D). Matrigel plugs containing D-3D contained more red blood cells than those containing S-3D. D-3D transplantation into ischemic mouse hind limbs prevented limb loss and augmented blood perfusion when compared to S-3D transplantation. Transplanted D-3D also revealed a high capillary density and angiogenic cytokine levels and transdifferentiated into endothelial-like cells in the hind limb muscle. These findings highlight the benefits of using the dual 3D culture system to optimize stem-cell-based therapeutic strategies, thereby advancing the therapeutic strategy for ischemic vascular disease and tissue regeneration.

BMP-2 Genome-Edited Human MSCs Protect against Cartilage Degeneration via Suppression of IL-34 in Collagen-Induced Arthritis.

Even though the regenerative potential of mesenchymal stem cells (MSCs) has been extensively studied, there is a debate regarding their minimal therapeutic properties. Bone morphogenetic proteins (BMP) are involved in cartilage metabolism, chondrogenesis, and bone healing. In this study, we aimed to analyze the role of genome-edited BMP-2 overexpressing amniotic mesenchymal stem cells (AMMs) in a mouse model of collagen-induced arthritis (CIA). The BMP-2 gene was synthesized and inserted into AMMs using transcription activator-like effector nucleases (TALENs), and BMP-2-overexpressing AMMs (AMM/B) were sorted and characterized using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The co-culture of AMM/B with tumor necrosis factor (TNF)-α-treated synovial fibroblasts significantly decreased the levels of interleukin (IL)-34. The therapeutic properties of AMM/B were evaluated using the CIA mouse model. The injection of AMM/B attenuated CIA progression and inhibited T helper (Th)17 cell activation in CIA mice. In addition, the AMM/B injection increased proteoglycan expression in cartilage and decreased the infiltration of inflammatory cells and factors, including IL-1ß, TNF-α, cyclooxygenase (COX)-2, and Nuclear factor kappa B (NF-kB) in the joint tissues. Therefore, editing the BMP-2 genome in MSCs might be an alternative strategy to enhance their therapeutic potential for treating cartilage degeneration in arthritic joints.

Dual CXCR4/IL-10 Gene-Edited Human Amniotic Mesenchymal Stem Cells Exhibit Robust Therapeutic Properties in Chronic Wound Healing.

Although stem cells have attracted attention as a novel therapeutic solution for tissue regeneration, their minimal efficacy remains controversial. In the present study, we aimed to investigate the enhanced therapeutic property of CXCR4/IL-10 dual angiogenic/anti-inflammatory gene knock-in amniotic mesenchymal stem cells (AMM) in a wound-healing model. Dual CXCR4 and IL-10 genes were inserted into the AMM genome using transcription-activator-like effector nuclease (TALEN). Matrigel tube formation and anti-inflammatory effects were assessed in vitro, and efficacy was tested in vivo in a diabetic wound-healing model. CXCR4/IL-10-expressing amniotic MSCs (AMM/CI) strongly expressed CXCR4 and IL-10 genes and robustly promoted tube formation and anti-inflammatory potential. AMM/CI transplantation resulted in accelerated wound healing, as well as high engraftment and re-epithelialization potential. Transplanted AMM/CI also exhibited high angiogenic and decreased pro-inflammatory gene expression in the wound tissue, indicating direct therapeutic effects on wound healing. Taken together, these data indicate that dual angiogenic/anti-inflammatory gene knock-in may be a novel approach to enhance the therapeutic effects of stem cells, and transplantation of AMM/CI can be an alternative therapeutic option in chronic wound healing.

Anti-Arthritogenic Property of Interleukin 10-Expressing Human Amniotic MSCs Generated by Gene Editing in Collagen-Induced Arthritis.

Although stem cells are promising tools for the treatment of arthritis, their therapeutic effects remain controversial. In this study, we investigated the therapeutic properties of interleukin (IL)-10-overexpressing human amniotic mesenchymal stem cells (AMMs) generated via gene editing in a collagen-induced mouse model. IL-10 was inserted into the genomic loci of AMMs via transcription activator-like effector nucleases. In vitro immunomodulatory effects of IL-10-overexpressing AMMs (AMM/I) were evaluated and their anti-arthritogenic properties were determined in collagen-induced arthritis (CIA) mice. Transplantation of AMM/I attenuates CIA progression. In addition, the regulatory T cell population was increased, while T helper-17 cell activation was suppressed by AMM/I administration in CIA mice. Consistently, AMM/I injection increased proteoglycan expression, while reducing inflammation and the expression levels of the pro-inflammatory factors, IL-1 ß, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor- α, in joint tissues. In conclusion, use of IL-10-edited human AMM/I may be a novel therapeutic strategy for the treatment of arthritis.

SDF-1-edited human amniotic mesenchymal stem cells stimulate angiogenesis in treating hindlimb ischaemia.

Although stem cells have extensively been studied as a novel vehicle for tissue repair, their sustained efficacy remains controversial. In this study, we aimed to investigate the angiogenic potency over time of stromal cell-derived factor-1 (SDF-1) gene-edited amniotic mesenchymal stem cells (AMM/S) in a hindlimb ischaemia model. An SDF-1 transgene was inserted into the AMM cell genome via transcription activator-like effector nuclease (TALEN) mediated knock-in, and cell migration, Matrigel tube formation, and in vivo Matrigel plug assays were performed. AMM/S were also transplanted into hindlimb ischaemia model mice. Blood perfusion, therapeutic potential, histology, capillary density and in vivo angiogenic assays were performed. AMM/S exhibited high expression of the SDF-1 gene, and robustly promoted migration, proliferation and microvascular formation. AMM/S transplantation significantly increased blood perfusion and limb loss prevention compared with AMM. AMM/S also significantly inhibited increased capillary density and expression of angiogenic factors in the ischaemic hindlimb. Our study demonstrated that AMM/S provides a significant therapeutic effect in ischaemic hindlimbs by enhancing angiogenesis.

Alleviation of Surgery-Induced Osteitis in Sinonasal Cavity by Dexamethasone-Loaded Poly(lactic-co-glycolic acid) (PLGA) Microparticles with Strong Calcium-Binding Affinity.

For the treatment of sinus surgery-induced osteitis in chronic rhinosinusitis (CRS), oral or intranasal administration of corticoids is generally used, although it has critical limitations and unavoidable side effects. To overcome these limitations, we designed dexamethasone (Dex)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles with bone-specific binding affinity, which could release the encapsulated Dex in a sustained manner on the exposed bone after the surgical wound in the nasal cavity. In a previous report, we prepared poly(butyl methacrylate-co-methacryloyloxyethyl phosphate) (PBMP) with both calcium-binding phosphomonoester groups and PLGA-binding butyl groups to introduce strong calcium-binding property to PLGA particles. In this study, after successful encapsulation of Dex in the PBMP-coated PLGA particles, we applied the Dex-PLGA/PBMP to the treatment of post-operative osteitis in the sinonasal cavity. The Dex-PLGA/PBMP showed more than 5-times higher binding affinity to the hydroxyapatite (HA) surface compared to the non-coated PLGA particles, without altering the morphology and encapsulation efficiency. After establishing the neo-osteogenesis mouse model by mechanical injury of the nasal mucosa, the activity of intranasally administered Dex-PLGA/PBMP was examined to inhibit the formation of undesirable new woven bone during the wound healing process. In addition, significantly lower osteocalcin activity was observed in the group treated with Dex-PLGA/PBMP, indicating decreased activation of osteoblasts. Overall, these results demonstrate that the PLGA/PBMP microparticle strategy has great potential for the treatment of CRS-related osteitis by localized corticoid delivery on the exposed bones with minimal side effects.

Genome Edited Sirt1-Overexpressing Human Mesenchymal Stem Cells Exhibit Therapeutic Effects in Treating Collagen-Induced Arthritis.

Even though mesenchymal stem cells (MSCs) are known for cartilage regeneration, their therapeutic efficacy needs to be enhanced. In the present study, we produced genome-edited silent information regulator 2 type 1 (Sirt1)-overexpressing MSCs, and evaluated their therapeutic potential in a damaged cartilage mouse liver fibrosis model. The Sirt1 gene was successfully inserted into a 'safe harbor' genomic locus in amniotic mesenchymal stem cells (AMMs), and the chondrogenic properties of the Sirt1 gene overexpressing AMMs (AMM/S) were characterized using quantitative PCR and histology. Therapeutic potentials were investigated in a collagen-induced arthritis (CIA) mouse model. Chondrocyte-differentiated AMM/S expressed cartilage-specific genes and were positive for Safranin O staining. Transplantation of AMM/S attenuated CIA progression and suppressed T helper (Th)-17 cell activation while increasing the Treg cell population in CIA mice. Pro-inflammatory factors, such as interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α were significantly decreased in AMM/S-injected joint tissues. In conclusion, genome-edited AMM/S may represent a safe and alternative therapeutic option for the treatment and repair of damaged cartilage, or in inflammatory joint arthritis.

TGF-ß1 overexpressing human MSCs generated using gene editing show robust therapeutic potential for treating collagen-induced arthritis.

Transforming growth factor ß (TGF-ß) plays a pivotal role in cartilage differentiation and other functions of mesenchymal stem cells (MSCs). In this study, we investigated the therapeutic potential of TGF-ß1 overexpressing amniotic MSCs (AMMs) generated using gene editing in a mouse model of damaged cartilage. The TGF-ß1 gene was inserted into a safe harbor genomic locus in AMMs using transcription activator-like effector nucleases. The chondrogenic properties of TGF-ß1-overexpressing AMMs (AMM/T) were characterized using reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR, and histological analysis, and their therapeutic effects were evaluated in mouse model of collagen-induced arthritis (CIA). AMM/T expressed cartilage-specific genes and showed intense Safranin O and Alcian blue staining. Furthermore, injecting AMM/T attenuated CIA progression compared with AMM injection, and increased the regulatory T (Treg) cell population, while suppressing T helper (Th)17 cell activation in CIA mice. Proinflammatory factors, such as interleukin-1ß (IL-1ß), IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α were significantly decreased in AMM/T injected CIA mice compared with their AMM injected counterparts. In conclusion, genome-edited AMMs overexpressing TGF-ß1 may be a novel and alternative therapeutic option for protecting cartilage and treating inflammatory joint arthritis.

Development of poly(D,L-lactic-co-glycolic acid) films coated with biomembrane-mimicking polymers for anti-adhesion activity.

A physical barrier is one of the most effective strategies to alleviate excessive postoperative adhesion (POA) between tissues at an injury site. To overcome the limitations of current polymeric film-type physical barriers, we suggest a film of poly(lactic-co-glycolic acid) (PLGA) that is non-covalently coated with poly(2-methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate (BMA)) (PMB). While maintaining the degradability and mechanical properties of PLGA, the PMB coating introduces strong anti-adhesive properties to the film by forming a zwitterionic MPC-based surface through the hydrophobic interactions between BMA moieties and PLGA. Compared to SurgiWrap®, the commercially available poly(lactic acid)-based anti-adhesive film against POA, the PMB-coated PLGA film is much more inhibitory against protein adsorption and fibroblast adhesion, processes that are crucial to the POA process. PMB coating also inhibits the expression of fibronectin containing extra domain A (FN-EDA), α-smooth muscle actin (α-SMA), and collagen type IV alpha 2 (COL4A2), which are marker genes and proteins involved in fibroblast activation and excessive fibrosis during POA. Such inhibitory activities are clearly observed in a 3-dimensional culture of fibroblasts within a collagen matrix, which mimics the in vivo environment of an injury site, as well as in a 2-dimensional culture. The kinetics and the stability of the PMB coating suggest potential future clinical use to coat PLGA films to create a film-type anti-adhesion barrier that overcomes the limitations of current products.

Three-dimensional Differentiated Human Mesenchymal Stem Cells Exhibit Robust Antifibrotic Potential and Ameliorates Mouse Liver Fibrosis.

Recently, three-dimensional (3D)-cultured adipose mesenchymal stem cells (ASCs) have provided an effective therapy for liver fibrosis. This study aimed to enhance the potential of human ASCs for antifibrosis or hepatocyte regeneration using a 3D culture system and investigate their therapeutic mechanism in experimental liver fibrosis. ASC-3Dc were generated in a 3D culture system and stimulated with four growth factors, namely epidermal growth factor, insulin-like growth factor (IGF)-1, fibroblast growth factor-2, and vascular endothelial growth factor-A. The expression levels of antifibrotic or hepatic regeneration factors were then measured using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The therapeutic effects of ASC-3Dc were determined using a liver fibrosis model induced by thioacetamide. Histological analysis was performed to elucidate the therapeutic mechanism. ASC-3Dc exhibited high levels of hepatocyte growth factor (HGF), IGF-1, stromal cell-derived factor (SDF)-1 genes, and protein expression. In addition, injecting ASC-3Dc significantly prevented hepatic fibrosis and improved liver function in vivo. Moreover, high numbers of ki-67-expressing hepatocytes were detected in the ASC-3Dc-injected livers. Albumin-expressing ASC-3Dc engrafted in fibrotic livers augmented HGF expression. Thus, short-term 3D-cultured ASCs may be a novel alternative to the conventional treatment for liver damage in clinical settings.

Application of attached algae flow-ways for coupling biomass production with the utilization of dilute non-point source nutrients in the Upper Laguna Madre, TX.

The purpose of this study is to determine the potential for an attached algae flow-way system to efficiently produce algal biomass in estuarine surface waters by utilizing dilute non-point source nutrients from local urban, industrial, and agricultural discharges into the Upper Laguna Madre, Corpus Christi, Texas. The study was conducted over the course of two years to establish seasonal base-line biomass productivity and composition for bioproducts applications, and to identify key environmental factors and flow-way cohorts impacting biomass production. For the entire cultivation period, continuous ash-free biomass production at 4 to 10 g/m2/day (corresponding to nutrient recovery at 300 to 500 mg of nitrogen/m2/day and 15 to 30 mg of phosphorus/m2/day) was successfully achieved without system restart. Upon start-up, a latency period was observed which indicates roles for species succession from relatively low productivity, high ash content pioneer periphytic culture composed primarily of benthic diatoms from the source waters to higher productivity, reduced ash content, and more resilient culture mainly composed of filamentous chlorophyta, Ulva lactuca. Principal Component Analysis (PCA) was used to identify environmental factors driving biomass production, and machine learning (ML) models were constructed to assess the predictive capability of the data set for system performance using the local multi-season environmental variations. Environmental datasets were segregated for ML training, validation, and testing using three methods: regression tree, ensemble regression, and Gaussian process regression (GPR). The predicted ash-free biomass productivity using ML models resulted in root-squared-mean-errors (RSME) from 1.78 to 1.86 g/m2/day, and R2 values from 0.67 to 0.75 using different methods. The greatest contributor to net productivity was total solar irradiation, followed by air temperature, salinity, and pH. The results of the study should be useful as a decision-making tool to application of attached algae flow-ways for biomass production while preventing algal blooms in the environment.

ASC and SVF Cells Synergistically Induce Neovascularization in Ischemic Hindlimb Following Cotransplantation.

Previously, we reported the angio-vasculogenic properties of human stromal vascular fraction (SVF) and adipose tissue-derived mesenchymal stem cells (ASCs). In this study, we investigated whether the combination of ASCs and SVF cells exhibited synergistic angiogenic properties. We conducted quantitative (q)RT-PCR, Matrigel plug, tube formation assays, and in vivo therapeutic assays using an ischemic hind limb mouse model. Immunohistochemical analysis was also conducted. qRT-PCR results revealed that FGF-2 was highly upregulated in ASCs compared with SVF, while PDGF-b and VEGF-A were highly upregulated in SVF. Conditioned medium from mixed cultures of ASCs and SVF (A+S) cells showed higher Matrigel tube formation and endothelial cell proliferation in vitro. A+S cell transplantation into ischemic mouse hind limbs strongly prevented limb loss and augmented blood perfusion compared with SVF cell transplantation. Transplanted A+S cells also showed high capillary density, cell proliferation, angiogenic cytokines, and anti-apoptotic potential in vivo compared with transplanted SVF. Our data indicate that A+S cell transplantation results in synergistic angiogenic therapeutic effects. Accordingly, A+S cell injection could be an alternative therapeutic strategy for treating ischemic diseases.

HGF and IL-10 expressing ALB::GFP reporter cells generated from iPSCs show robust anti-fibrotic property in acute fibrotic liver model.

BACKGROUND: Cell therapy using hepatocytes derived from stem cells has been regarded as a promising alternate to liver transplantation. However, the heterogeneity of these hepatocytes makes them unsuitable for therapeutic use. To overcome this limitation, we generated homogenous hepatocyte like induced hepatocyte-like (iHep) cells. METHODS: iHep cells were generated from induced pluripotent stem cells (iPSCs) integrated with the albumin (ALB) reporter gene. The therapeutic properties of these iHep cells were investigated after transplantation in fibrotic liver tissues of a mouse model. RESULTS: The iHep cells expressed hepatocyte specific genes and proteins, and exhibited high levels of hepatocyte growth factor (HGF) and interleukin (IL)-10 expressions. Transplantation of iHep cells significantly decreased thioacetamide (TAA)-induced liver fibrosis, apoptotic cells in the liver, and ameliorated abnormal liver function. Liver tissues engrafted with iHep cells exhibited decreased expression of pro-inflammatory factors such as transforming growth factor (TGF)-ß, IL-6, and monocyte chemo attractant protein (MCP)-1. Furthermore, an increased number of proliferating hepatocytes and human albumin-expressing iHep cells were detected in mice liver. CONCLUSIONS: This study has investigated and proven the liver regeneration potential of genome-edited iHep cells and promises to be a strong foundation for further studies exploring cell therapy as an alternative therapeutic option for the treatment of liver fibrosis.

4-Methoxyphenyl (E)-3-(Furan-3-yl) Acrylate Inhibits Vascular Smooth Muscle Cell Proliferation.

The Cordyceps extract exhibits antiproliferative potential in vascular smooth muscle cells (SMCs) through the mitogen-activated protein kinase signaling pathway. In this study, we aimed to identify the active compounds in the Cordyceps extract and analyze their role in remodeling the arterial wall. On investigation, we discovered the following active compound: 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate and synthesized it. We performed antiproliferation and antimigration assays in addition to an in vivo vessel wall remodeling experiment. Investigation of the mechanism adopted by the active compound to remodel the vessel was performed. The newly synthesized compound inhibited the proliferation and migration of SMCs. Treatment with the synthesized compound reduced neointima formation in the balloon-injured Sprague-Dawley rat model. In addition, this compound inhibited the activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 in type I collagen-activated SMCs. Moreover, this compound suppressed the expression of cycloxygenase-2 (COX-2) in SMCs. Therefore, this compound can exert potential antiarteriosclerotic effects by modulating vessel wall remodeling. In conclusion, the newly synthesized 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate might be an alternative therapeutic intervention for the treatment of atherosclerosis.

Directly induced hepatogenic cells derived from human fibroblast ameliorate liver fibrosis.

Recently, reprogramming technology has emerged as a fascinating tool to generate specific tissue cells. In this study, we tested the hypothesis that ultrasound-directed cellular reprogramming can generate fibroblasts into hepatogenic cells. We directly induced human dermal fibroblasts (HDFs) into hepatocyte-like cells mediated by environmental transition-guided cellular reprogramming (h/entr) using ultrasound. We confirmed the characteristics of h/entr by the expression levels of hepatocyte specific RNA and proteins. The effects of h/entr on the activation of hepatic stellate cells were analyzed using conditioned medium (CM). h/entr were transplanted into mice with acute liver fibrosis and the therapeutic effects and mechanism of liver fibrosis were determined. h/entr exhibited high levels of hepatocyte specific genes, hepatogenic (hepatocyte growth factor [HGF], colony-stimulating factor 3 [CSF-3]) and anti-inflammatory (interleukin 10 [IL-10]) factors. h/entr CM suppressed the activation of hepatic stellate cells in vitro. Transplantation of h/entr significantly delayed liver fibrosis and improved liver function. Transplantation of h/entr accelerates liver regeneration, and human albumin expressing h/entr and human Alu gene were detected in the mouse livers. This report suggests that directly induced h/entr could be one of the highly effective therapeutic options for the treatment of liver cirrhotic disease.

Minicircle-based GCP-2 ex vivo gene therapy enhanced the reepithelialization and angiogenic capacity.

Recently, minicircle (MC)-based cell therapy has been emerging as a novel technology for nonviral genetic modification. In this study, we investigated the characteristics of granulocyte chemotactic protein-2 (GCP-2)-overexpressing fibroblasts (GCP-2/MC) using MC microporation technology, as well as its therapeutic mechanism in wound healing. GCP-2 parent plasmid and MC containing GCP-2 were generated. Human dermal fibroblasts (HDF) were transfected with MC containing GCP-2. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), scratch wound assay, and in vivo wound healing assay were performed. Gene and protein expression analysis revealed that GCP-2/MC highly expressed epithelialization growth factor, epidermal growth factor (EGF), chemokines, GCP-2, interleukin (IL)-8, as well as wound healing-associated genes such as insulin growth factor (IGF)-1 and hepatocyte growth factor (HGF). An in vitro scratch wound closure and matrigel tube formation assays demonstrated that the culture medium derived from GCP-2/MC substantially accelerated the wound closure and matrigel network formation. Wounds in nude mice were created by skin excisions followed by injections of GCP-2/MC. Results showed high cell survival potential and that GCP-2/MC transplantation highly accelerated skin wound closure by increasing reepithelialization, capillary density, and enhancing angiogenic factors, suggesting direct benefits for cutaneous closure. Taken together, these data suggest that MC-based GCP-2 overexpression could be a promising alternative strategy for promoting wound healing.

Necessity of the Needs Map in the Service Design for Smart Cities.

Recently, the issue of how to involve actual service users in the service designs for Smart cities has grown in importance, as this is a key factor in determining the serviceability and sustainability of developed services. Reckless participation of users can make the service design process inefficient and cause a cost increase. So, in this study, we propose the needs map which can be applied to various stages of service development and help service designers to make efficient and reasonable decisions without being too time-consuming. The proposed needs map is a schematization of theoretical concepts for Smart city planning in accordance with the framework of service-technology-infrastructure-management (STIM). Through the needs map, various urban problems, statistical data, and users' needs in a smart city are classified and analyzed concept by concept, and these focused analysis results suggest a proper direction to researchers in the service development plan. To demonstrate experimentally the feasibility of the needs map, we applied it in practice to a service design for the Smart city experience zone located in Daejeon, South Korea.

Synthesis of poly(disulfide)s with narrow molecular weight distributions via lactone ring-opening polymerization.

We report the first example of controlled polymerization of poly(disulfide)s with narrow molecular weight distributions. 1,4,5-oxadithiepan-2-one (OTP), a disulfide-containing 7-membered ring lactone, was polymerized by using the diphenylphosphate (DPP) catalyzed lactone ring-opening polymerization method. The polymerization proceeded in a living manner, and the resulting polymers displayed very narrow polydispersity index (PDI) values below 1.1 and excellent backbone degradability responding to reducing conditions and UV irradiation.

Transplantation of human adipose tissue derived-SVF enhance liver function through high anti-inflammatory property.

Although human adipose tissue-derived stromal vascular fraction (SVF) has been considered a promising source of stem cells, its characteristics relevant to treatment of a damaged liver have not been fully elucidated. In the present study, we sought to characterize the property of human SVF and determine the therapeutic utility of SVF in the liver cirrhosis model. We performed microarray, quantitative (q)-PCR experiments, and in vivo therapeutic assays using a liver cirrhotic mouse model. q-PCR results revealed that hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)-A, Interleukin (IL)-10 and microRNA (miR)-146 were more highly upregulated in SVF than in human adipose-derived mesenchymal stem cells (ASCs). The SVF culture medium (CM) inhibited the activation of hepatic stellate cells in vitro. Injection of SVF significantly suppressed TAA-induced liver fibrosis and repaired liver function by inhibition of infiltrating inflammatory cells and induction of capillary/hepatocyte regeneration in vivo. Injection of IL-10 siRNA treated SVF cells decreased anti-inflammation and anti-fibrotic effects in TAA-induced mice liver. Our data indicate that SVF show a high anti-inflammatory property for treating fibrotic liver diseases through IL-10 secretion. Therefore, SVF might be a novel therapeutic alternative for the treatment of liver cirrhosis in clinical settings.