Fibroblast function recovery through rejuvenation effect of nanovesicles extracted from human adipose-derived stem cells irradiated with red light.

Fibroblasts (hDFs) are widely employed for skin regeneration and the treatment of various skin disorders, yet research were rarely investigated about restoration of diminished therapeutic efficacy due to cell senescence. The application of stem cell and stem cell-derived materials, exosomes, were drawn attention for the restoration functionality of fibroblasts, but still have limitation for unintended side effect or low yield. To advance, stem cell-derived nanovesicle (NV) have developed for effective therapeutic reagents with high yield and low risk. In this study, we have developed a method using red light irradiated human adipose-derived stem cells (hADSCs) derived NV (R-NVs) for enhancing the therapeutic efficacy and rejuvenating hDFs. Through red light irradiation, we were able to significantly increase the content of stemness factors and angiogenic biomolecules in R-NVs. Treatment with these R-NVs was found to enhance the migration ability and leading to rejuvenation of old hDFs to levels similar to those of young hDFs. In subsequent in vivo experiments, the treatment of old hDFs with R-NVs demonstrated a superior skin wound healing effect, surpassing that of young hDFs. In summary, this study successfully induced rejuvenation and leading to increased therapeutic efficacy to R-NVs treated old hDFs previously considered as biowaste.

Enhancing viability and angiogenic efficacy of mesenchymal stem cells via HSP90α and HSP27 regulation based on ROS stimulation for wound healing.

Light-based therapy has been reported as a potential preconditioning strategy to induce intracellular reactive oxygen species (ROS) signaling and improve the angiogenic properties of various types of cells. However, bio-stimulation mechanisms of light therapy in terms of ROS-heat shock proteins (HSPs) mediated anti-apoptotic and angiogenic pathways in human adult stem cells have not been fully delineated yet. Commonly used light sources such as light-emitting diode (LED) and laser are accompanied by drawbacks, such as phototoxicity, thermal damage, and excessive ROS induction, so the role and clinical implications of light-induced HSPs need to be investigated using a heat-independent light source. Here, we introduced organic LED (OLED) at 610 nm wavelength as a new light source to prevent thermal effects from interfering with the expression of HSPs. Our results showed that light therapy using OLED significantly upregulated anti-apoptotic and angiogenic factors in human bone marrow mesenchymal stem cells (hMSCs) at both gene and protein levels via the activation of HSP90α and HSP27, which were stimulated by ROS. In a mouse wound-closing model, rapid recovery and improved re-epithelization were observed in the light-treated hMSCs transplant group. This study demonstrates that the upregulation of Akt (protein kinase B)-nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, caused by HSP90α and HSP27 expression, is the mechanism behind the anti-apoptotic and angiogenic effects of OLED treatment on stem cells.

Fibronectin-Enriched Interface Using a Spheroid-Converged Cell Sheet for Effective Wound Healing.

Cell sheets and spheroids are cell aggregates with excellent tissue-healing effects. However, their therapeutic outcomes are limited by low cell-loading efficacy and low extracellular matrix (ECM). Preconditioning cells with light illumination has been widely accepted to enhance reactive oxygen species (ROS)-mediated ECM expression and angiogenic factor secretion. However, there are difficulties in controlling the amount of ROS required to induce therapeutic cell signaling. Here, we develop a microstructure (MS) patch that can culture a unique human mesenchymal stem cell complex (hMSCcx), spheroid-attached cell sheets. The spheroid-converged cell sheet structure of hMSCcx shows high ROS tolerance compared to hMSC cell sheets owing to its high antioxidant capacity. The therapeutic angiogenic efficacy of hMSCcx is reinforced by regulating ROS levels without cytotoxicity using light (610 nm wavelength) illumination. The reinforced angiogenic efficacy of illuminated hMSCcx is based on the increased gap junctional interaction by enhanced fibronectin. hMSCcx engraftment is significantly improved in our novel MS patch by means of ROS tolerative structure of hMSCcx, leading to robust wound-healing outcomes in a mouse wound model. This study provides a new method to overcome the limitations of conventional cell sheets and spheroid therapy.

Morus alba Root Extract Induces the Anagen Phase in the Human Hair Follicle Dermal Papilla Cells.

Restoring hair follicles by inducing the anagen phase is a promising approach to prevent hair loss. Hair follicle dermal papilla cells (HFDPCs) play a major role in hair growth via the telogen-to-anagen transition. The therapeutic effect of Morus alba activates ß-catenin in HFDPCs, thereby inducing the anagen phase. The HFDPCs were treated with M. alba root extract (MARE) to promote hair growth. It contains chlorogenic acid and umbelliferone and is not cytotoxic to HFDPCs at a concentration of 20%. It was demonstrated that a small amount of MARE enhances growth factor secretion (related to the telogen-to-anagen transition). Activation of ß-catenin was observed in MARE-treated HFDPCs, which is crucial for inducing the anagen phase. The effect of conditioned medium derived from MARE-treated HFDPCs on keratinocytes and endothelial cells was also investigated. The findings of this study demonstrate the potency of MARE in eliciting the telogen-to-anagen transition.

Poly(amino ester)-Based Polymers for Gene and Drug Delivery Systems and Further Application toward Cell Culture System.

Various synthetic polymers based on poly(amino ester) (PAE) are suggested as candidates for gene and drug delivery owing to their pH-responsiveness, which contributes to efficient delivery performance. PAE-based pH-responsive polymers are more biodegradable and hydrophilic than other types of pH-responsive polymers. The functionality of PAE-based polymers can be reinforced by using different chemical modifications to improve the efficiency of gene and drug delivery. Additionally, PAE-based polymers are used in many ways in the biomedical field, such as in transdermal delivery and stem cell culture systems. Here, the recent novel PAE-based polymers designed for gene and drug delivery systems along with their further applications toward adult stem cell culture systems are reviewed. The synthetic tactics are contemplated and pros and cons of each type of polymer are analyzed, and detailed examples of the different types are analyzed.