https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/15 2026-04-13T12:44:03Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/77722 Title: Human Adipose Stem Cells Engineered to Express Carboxylesterase Confer Anti-Tumoral Efficacy of Irinotecan in Castration-Resistant Prostate Cancer Bone Metastasis Growth and Osteolysis Authors: Yun, Da Hyun; Kim, Jae Heon; Lee, Sang Hun; Lee, Eun Jung; Park, Serk In; Song, Yun Seob Abstract: Purpose: Castration-resistant prostate cancer (CRPC) presents a significant clinical challenge, particularly when it metastasizes to bone, leading to skeletal-related events such as osteolysis. Conventional therapies offer limited efficacy and high toxicity, highlighting the need for innovative treatments. This study investigates the use of human telomerase reverse transcriptaseimmortalized adipose-derived stem cells engineered to express carboxylesterase (hTERT-ADSC.CE) to enhance the local activation and efficacy of irinotecan (CPT-11) in targeting CRPC. Materials and Methods: hTERT-ADSC.CE1 and hTERT-ADSC.CE2 cells were generated by lentiviral transduction with two genes encoding carboxylesterase enzymes CES1 or CES2 (referred to as CE1 or CE2 in this manuscript), respectively. The migration of hTERT-ADSC.CE1 and hTERT-ADSC.CE2 cells toward prostate cancer cells was evaluated in a transwell migration assay. The cytotoxicity of irinotecan in combination with hTERT-ADSC.CE1 and hTERT-ADSC.CE2 cells on PC3 prostate cancer cells was assessed via MTT viability and apoptosis assays. An in vivo CRPC bone metastasis model in mice was used to examine the therapeutic effects of co-administered hTERT-ADSC.CE2 cells and CPT-11 on tumor growth and tumor-induced osteolysis. Results: hTERT-ADSC.CE1 and hTERT-ADSC.CE2 cells demonstrated selective migration toward PC3 cells and significantly enhanced the cytotoxic effects of CPT-11 on prostate cancer cells in vitro vitro. In vivo vivo, the combined treatment with hTERT-ADSC.CE2 and CPT-11 significantly reduced tumor growth and osteolytic activity in the bone metastasis model. Histological analysis confirmed increased apoptosis in tumor cells and reduced osteolysis, indicating effective local drug activation by hTERT-ADSC.CE1 and/or hTERT-ADSC.CE2. Conclusions: Our findings suggest that hTERT-ADSC.CE1 and hTERT-ADSC.CE2 cells combined with irinotecan offer a promising targeted therapy for CRPC, enhancing drug efficacy while minimizing systemic toxicity. This cell-based enzyme-prodrug therapy could address the limitations of current therapies, especially in bone metastatic CRPC, and warrants further investigation for clinical translation. 2026-04-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79436 Title: Therapeutic reprogramming of circulating myeloid cells via signal regulatory protein a extracellular vesicles in acute kidney injury Authors: Shin, Dong-U; Jo, Min Kyoung; Kwon, Minjeong; Jeong, Yewon; Cho, Bogyeong; Kim, Seong A.; Choi, Ga-Eun; Kim, Seohyun; Song, Seok Ho; Joo, Hyemin; KIM, Hyun Jung; Lee, Jung Pyo; Lee, Jeonghwan; Kim, In-San; Nam, Gi Hoon Abstract: Introduction: Acute kidney injury (AKI) presents significant clinical challenges, with high mortality and progression risk to chronic kidney disease. Mechanisms remain incompletely understood and disease-specific therapies are lacking. Recent evidence highlights the pivotal role of infiltrating myeloid cells in perpetuating kidney inflammation. CD47, a key cell surface immune checkpoint protein, is upregulated in inflammation and regulates myeloid cell infiltration, making it an attractive therapeutic target. Methods: Single-cell RNA sequencing and CD47 protein staining were used to identify CD47 expressions in human AKI specimens and two mouse models (cis-platin and bilateral ischemia/reperfusion). To therapeutically exploit this, we engineered extracellular vesicles (EVs) from human bone marrow mesenchymal stem cells to express a high-affinity signal regulatory protein a (SIRP alpha) variant (SIRP-EVs), the ligand for CD47. The efficacy of SIRP-EVs was evaluated in murine AKI models. Results: CD47 expression was significantly elevated in myeloid populations, particularly macrophages, in both human AKI tissues and mouse models. A single systemic administration of SIRP-EVs in murine AKI models exhibited therapeutic effects, including improved kidney function markers, reduced pro-inflammatory cytokine production, and ameliorated kidney histopathology. Mechanistically, SIRP-EVs preferentially localize to circulating myeloid cells, modulate CD47 expression, and subsequently inhibit their migration into injured kidney tissue. Moreover, single cell transcriptomics revealed that SIRP-EV treatment reprograms circulating macrophages toward pro-resolving phenotypes, characterized by upregulation of genes associated with tissue repair. Conclusions: Targeting CD47 on circulating myeloid cells with SIRP-EVs provides a systemic, blood-focused immunomodulatory strategy that precedes tissue infiltration, contrasting with conventional tissue-centric approaches. Our findings support SIRP-EVs as a promising therapeutic option for AKI and potentially other inflammation-driven diseases through selective modulation and reprogramming of peripheral myeloid cells. 2026-03-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79565 Title: Stimuli-Responsive Hydrogels: From Swelling-Deswelling Mechanisms to Biomedical Applications Authors: Kim, Meyoung-Kon; Lee, Junghan; Kang, A-Ram Abstract: Stimuli-responsive hydrogels, also referred to as "smart" hydrogels, have emerged as versatile platforms for a wide range of biological and biomedical applications owing to their tunable physical, chemical, and biocompatible properties. Their adaptability arises from both their ability to undergo reversible swelling-deswelling and volume phase transitions in response to specific physicochemical or biological stimuli and the diversity of synthesis strategies that enable precise tailoring of material properties to meet distinct biomedical demands. Recent advances have led to the development of novel hydrogel designs with improved swelling-deswelling behavior, enhanced stimulus sensitivity, and superior biocompatibility, thereby expanding their applicability in complex biological environments. Despite this progress, challenges such as precise control over hydrogel size and relatively slow response kinetics remain critical barriers to broader biomedical and clinical translation. Addressing these limitations requires strategies, including reducing hydrogel particle dimensions to accelerate response rates and engineering heterogeneous or highly porous gel architectures to increase functional surface area. This review provides a comprehensive classification of stimuli-responsive hydrogels based on their physical properties and response mechanisms, and summarizes recent innovations in their design, synthesis, and biomedical applications. Furthermore, it discusses emerging approaches to enhance the clinical applicability of smart hydrogels in controlled drug release, targeted gene delivery, biosensor development, and tissue engineering. Overall, continued optimization of swelling-deswelling characteristics and material design will be essential to fully realize the potential of stimuli-responsive hydrogels in precision medicine and advanced therapeutic applications. 2026-03-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/78838 Title: Breaking barriers: Engineering extracellular vesicles for enhanced endosomal escape and therapeutic delivery Authors: Kim, Jihong; Ha Hwang, Yeong; Nam, Gi-Hoon; Kim, In-San Abstract: Extracellular vesicles (EVs) have emerged as promising natural nanocarriers with superior biocompatibility, immune tolerance, and tissue tropism compared to synthetic nanoparticles. However, despite their efficient cellular uptake, the clinical translation of EV-based therapeutics is fundamentally constrained by inefficient endosomal escape, which remains the principal bottleneck to achieving functional cytosolic delivery. To address this challenge, a variety of engineering strategies have been developed, including post-isolation surface decoration with peptides and polymers, genetic incorporation of fusogenic proteins and channel-forming modules, and biophysical remodeling of membrane lipid composition. These modifications aim to enhance intracellular delivery by improving membrane fusion and facilitating endosomal membrane destabilization. Concurrently, the development of advanced quantitative assays has enabled more accurate evaluation of endosomal escape efficiency. This review summarizes recent advances in engineering approaches and analytical methodologies and discusses future perspectives for overcoming biological and manufacturing hurdles to realize the clinical potential of EV-based therapeutics. 2026-01-01T00:00:00Z