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Ion releasing nanoparticles to increase the wound healing efficacy of stem cell
임광범,정의영,유태경,방석호 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.1
Herein, we investigated that Fe ion can be delivered into hMSCs using pH-sensitive gold-iron nanoparticles (AuFe NPs) to enhance angiogenic paracrine factor secretion. Based on the different redox potential of Au and Fe, only Fe ion released from AuFe NPs whereas Au remained intact at low pH condition. The low pH (pH 4.5-5.5) condition of the endosomes made Fe ion release from the AuFe NPs. Treatment with AuFe NPs increased the ROS level in hMSCs through Fe ion release. Intracellular delivery of Fe ion to hMSCs promoted hypoxia-inducible factor-1 alpha expression, which could trigger the secretion of angiogenic growth factors such as, VEGF, FGF2, CXCR4, and CXCL12. Compared to hMSCs without AuFe NPs treatment, hMSCs treated AuFe NPs showed significantly enhanced angiogenic gene expression. Also, hMSCs with AuFe NPs treatment promoted angiogenesis and therapeutic efficacy in mouse wound closing model compared to no treatment or the conventional hMSCs group.
임광범,송지훈,현지유,방석호 한국고분자학회 2021 한국고분자학회 학술대회 연구논문 초록집 Vol.46 No.1
Keratinocytes are frequently used for the biological and biomedical remodeling of damaged skin tissues. However, low cell viability, poor cell maintenance, and lack of paracrine factors hamper the therapeutic efficacy of keratinocytes for skin wound healing. Here, we report the fabrication of a 2D and 3D co-spatial compartmentalized patch (CSCP) for a microscale keratinocyte- engineering platform and a novel method for delivering keratinocytes to enhance wound closure compared to that achieved by the conventional keratinocyte delivery method.
Fortifying the angiogenic efficacy of adipose derived stem cell spheroids using spheroid compaction
임광범,김성원,방석호 한국공업화학회 2021 Journal of Industrial and Engineering Chemistry Vol.93 No.-
Transplantation of stem cell spheroids to ischemic tissues has been suggested as an effective method fortreating ischemic disease, but its therapeutic efficacy varies according to the preparation methods forspheroids. We hypothesized that increasing cell compaction while preparing spheroids could improvethe angiogenic efficacy of spheroids. Optimized human adipose derived stem cell (hADSC) spheroidswere shown to upregulate cell adhesion molecule, and angiogenic paracrine factors expression withdownregulated senescence and apoptotic markers expression. We noted that the low seeding density(1104 cells (10KS)) had a far lower probability of forming spheroids than higher seeding densities(3 104 cells (30KS) and 1105 cells (100KS)). The 30KS spheroids demonstrated higher cell density andexpression levels of the angiogenic paracrine factor expression compared to those of 100 KS spheroids. 30KS spheroids with additional incubation (A30KS) showed significantly increased angiogenic paracrinefactors and cell adhesion molecule expressions with decreased senescence expression compared to thosein 30KS spheroids. Transplanting A30KS spheroids showed significantly enhanced therapeuticangiogenesis in mouse hindlimb ischemia model compared to conventional spheroid transplantation. This study successfully defined a set of novel criteria for spheroid culture, which may contribute to futurestem cell therapies.
임광범,정의영,유태경,방석호 한국공업화학회 2020 한국공업화학회 연구논문 초록집 Vol.2020 No.-
Here, we report that Fe ions can be delivered into human multipotent mesenchymal stem cells (hMSCs) using bioreducible metal nanoparticles (NPs) to enhance the angiogenic and cell homing efficacy of hMSCs by controlling ion-triggered intracellular reactive oxygen species (ROS) along with improved cell migration and reduced cytotoxicity. Treatment with the optimized amount of AuFe NPs led to a mild increment in intracellular ROS levels in hMSCs. As a result, Fe ions delivered to hMSCs additionally enhanced the expression of HIF-1 α induced by mild ROS generation. Compared with hMSCs without treatment, hMSCs treated with AuFe NPs showed significantly enhanced expressions of angiogenesis and lesion-targeting related genes and proteins. Transplantation of AuFe NPs-treated hMSCs in mice led to significantly enhanced angiogenesis and tissue regeneration in a wound-closing mouse model compared with no treatment or conventional hMSC transplantation.
임광범,김영환,김유진,김성원,유태경,방석호 한국공업화학회 2020 한국공업화학회 연구논문 초록집 Vol.2020 No.-
This research demonstrated the effect of using AuFe nanoparticles (NPs) and the availability of high passage number adult stem cells in wound healing using the nanoparticles. Treatment of high passage number hMSCs with AuFe NPs significantly enhanced the secretion of angiogenic paracrine factors and the expression of antiapoptotic genes compared to that in high passage number hMSCs without AuFe NPs treatment. Accordingly, the conditioned medium (CM) collected from AuFe NP-treated high passage number hMSCs dramatically enhanced the wound healing in a mouse. Our result implies that AuFe NPs treatment of high passage number stem cells could suggest a new platform for collecting therapeutically efficient CM.
Recent research trend in cell and drug delivery system for type 1 diabetes treatment
임광범,방석호 한국약제학회 2018 Journal of Pharmaceutical Investigation Vol.48 No.2
This review article summarizes the recent research trends for the treatment of type 1 diabetes (T1D) based on islets transplantation and drug delivery system. The research concerns ongoing development and future suggestions in T1D treatment with their limitations. T1D is one of the representative chronic disease causing human death with hypoglycemia and ketoacidosis. As the T1D incidence rate and market size increase, the need for T1D treatment is growing worldwide. Islets transplantation and drug delivery system with or without insulin have shown the potentials for effective T1D treatment. This review discusses various recent methods for islets transplantation derived from human stem cells or animal tissue. In addition to cell transplantation methods, islet transplantation with other cells or biomaterials that can deliver insulin or non-insulin drugs simultaneously are discussed. There are several limitations in the use of conventional islet and drug delivery system based on insulin and non-insulin for T1D treatment. This manuscript reviews the recent research results based on limelight research subjects about T1D treatment and their limitations.
김영환,임광범,방석호 한국공업화학회 2019 한국공업화학회 연구논문 초록집 Vol.2019 No.0
Here, we report that Fe ion can be delivered into human mesenchymal stem cells (hMSCs) using bioreducible inorganic nanoparticle to enhance angiogenic paracrine factor secretion along with the improved cell migration capacity without causing cytotoxicity. Fe ion release from bioreducible inorganic nanoparticles was designed to be pH-sensitive manner so that low pH (pH 4.5-5.5) condition of the endosomes could start in situ Fe ion release from the nanoparticles. Treatment with AuFe NPs led mild level of reactive oxygen species increment in hMSCs through Fe ion released from our novel gold-iron nanoparticles (AuFe NPs). Fe ion delivered to hMSCs enhanced hypoxia-inducible factor-1 alpha expression which is a key factor of triggering angiogenic growth factor secretion from hMSCs. Compared to hMSCs without AuFe NPs treatment, hMSCs treated AuFe NPs resulted in significantly enhanced angiogenic growth factors.
김영환,정의영,임광범,김유진,Kim Sung-Won,Jeong Gun-Jae,Jang Young Charles,박경민,김동익,유태경,방석호 나노기술연구협의회 2020 Nano Convergence Vol.7 No.34
Cell therapy based on human adipose derived stem cells (hADSCs) is a known potential therapeutic approach to induce angiogenesis in ischemic diseases. However, the therapeutic efficacy of direct hADSC injection is limited by a low cell viability and poor cell engraftment after administration. To improve the outcomes of this kind of approach, various types of nanoparticles have been utilized to improve the therapeutic efficacy of hADSC transplantation. Despite their advantages, the adverse effects of nanoparticles, such as genetic damage and potential oncogenesis based on non-degradable property of nanoparticles prohibit the application of nanoparticles toward the clinical applications. Herein, we designed a transition metal based inorganic nanocluster able of pH-selective degradation (ps-TNC), with the aim of enhancing an hADSC based treatment of mouse hindlimb ischemia. Our ps-TNC was designed to undergo degradation at low pH conditions, thus releasing metal ions only after endocytosis, in the endosome. To eliminate the limitations of both conventional hADSC injection and non-degradable property of nanoparticles, we have collected conditioned medium (CM) from the ps-TNC treated hADSCs and administrated it to the ischemic lesions. We found that intracellular increment of transition metal ion upregulated the hypoxia-inducible factor 1α, which can induce vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expressions. Based on the molecular mechanism, the secretion of VEGF and bFGF by ps-TNC treated hADSCs showed a significant improvement compared to that of untreated cells. Injecting the CM collected from ps-TNC treated hADSCs into the mouse hindlimb ischemia model (ps-TNC-CM group) showed significantly improved angiogenesis in the lesions, with improved limb salvage and decreased muscle degeneration compared to the group injected with CM collected from normal hADSCs (CM group). This study suggests a novel strategy, combining a known angiogenesis molecular mechanism with both an improvement on conventional stem cell therapy and the circumvention of some limitations still present in modern approaches based on nanoparticles.