Corneal neovascularization (CNV) is a heavy attribute of blinding disease changes. Existing medications need numerous infusions and have a limited absorption. Investigating novel drugs with safety, efficacy, and convenience is crucial. In this study, we developed a bone morphogenetic protein 4 (BMP4)-loaded poloxamer-oxidized sodium alginate (F127-OSA) thermosensitive hydrogel. The 14 % F127-OSA hydrogel transformed from sol to gel at 31-32 °C, which might extend the application period on the ocular surface. The hydrogel's porous structure and uniform dispersion made it possible for drugs to release gradually. We used a suture-induced rat CNV model to investigate the mechanism of CNV inhibition by hydrogel. We discovered that F127-OSA hydrogel loaded with BMP4 could significantly reduce the length and area of CNV, relieve corneal edema, and stop aberrant epithelial cell proliferation. The hydrogel's efficacy was superior to that of the common solvent group. Additionally, BMP4 thermosensitive hydrogel repaired ultrastructure, including microvilli, intercellular junctions, and damaged apical junctional complexes (AJCs), suggesting a potential mechanism by which the hydrogel prevented CNV formation. In conclusion, our investigation demonstrates that F127-OSA thermosensitive hydrogel loaded with BMP4 can repair corneal epithelial AJCs and is a promising novel medication for the treatment of CNV.

2023-07-26·World journal of stem cells

Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing.

Article

作者: He, Wen-Jun ; Li, Ke ; Wu, Li-Jun ; Liu, Xiao ; Shi, Yuan ; Lin, Wei ; Liu, Jian-Jiang ; Chen, Wei-Xin

BACKGROUNDCurrent evidence shows that human induced pluripotent stem cells (hiPSCs) can effectively differentiate into keratinocytes (KCs), but its effect on skin burn healing has not been reported.AIMTo observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms.METHODSAn analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926, and GSE27186 was established. A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs. The expression of KCs marker proteins was detected using immunofluorescence staining. A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created, and then phosphate buffered saline (PBS), hiPSCs-KCs, or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface. The wound healing, re-epithelialization, engraftment of hiPSCs-KCs into wounds, proinflammatory factor level, and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining, carboxifluorescein diacetate succinimidyl ester (CFSE) fluorescence staining, enzyme linked immunosorbent assay, and Western blotting on days 3, 7, and 14 after the injection, respectively. Moreover, the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry, EdU, Transwell, and damage repair assays.RESULTSHiPSCs-KCs could express the hallmark proteins of KCs. COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs. Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area, an increase in wound re-epithelialization, a decrease in proinflammatory factors content, and an inhibition of NF-κB pathway activation compared to the PBS group. The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration, providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration.CONCLUSIONIn deep, second-degree burn wounds, COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.

2023-04-21·International journal of molecular sciences

Inflammatory Response and Exosome Biogenesis of Choroid Plexus Organoids Derived from Human Pluripotent Stem Cells

Article

作者: Arthur, Peggy ; Singh, Mandip ; Wang, Xueju ; Muok, Laureana ; Esmonde, Colin ; Li, Yan ; Driscoll, Tristan ; Liu, Chang ; Chen, Xingchi

The choroid plexus (ChP) is a complex structure in the human brain that is responsible for the secretion of cerebrospinal fluid (CSF) and forming the blood-CSF barrier (B-CSF-B). Human-induced pluripotent stem cells (hiPSCs) have shown promising results in the formation of brain organoids in vitro; however, very few studies to date have generated ChP organoids. In particular, no study has assessed the inflammatory response and the extracellular vesicle (EV) biogenesis of hiPSC-derived ChP organoids. In this study, the impacts of Wnt signaling on the inflammatory response and EV biogenesis of ChP organoids derived from hiPSCs was investigated. During days 10-15, bone morphogenetic protein 4 was added along with (+/-) CHIR99021 (CHIR, a small molecule GSK-3β inhibitor that acts as a Wnt agonist). At day 30, the ChP organoids were characterized by immunocytochemistry and flow cytometry for TTR (~72%) and CLIC6 (~20%) expression. Compared to the -CHIR group, the +CHIR group showed an upregulation of 6 out of 10 tested ChP genes, including CLIC6 (2-fold), PLEC (4-fold), PLTP (2-4-fold), DCN (~7-fold), DLK1 (2-4-fold), and AQP1 (1.4-fold), and a downregulation of TTR (0.1-fold), IGFBP7 (0.8-fold), MSX1 (0.4-fold), and LUM (0.2-0.4-fold). When exposed to amyloid beta 42 oligomers, the +CHIR group had a more sensitive response as evidenced by the upregulation of inflammation-related genes such as TNFα, IL-6, and MMP2/9 when compared to the -CHIR group. Developmentally, the EV biogenesis markers of ChP organoids showed an increase over time from day 19 to day 38. This study is significant in that it provides a model of the human B-CSF-B and ChP tissue for the purpose of drug screening and designing drug delivery systems to treat neurological disorders such as Alzheimer's disease and ischemic stroke.

100 项与 BMP-4 (Ascenion) 相关的药物交易

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