https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/15 2026-04-04T09:43:09Z 2026-04-04T09:43:09Z Yun, Da Hyun Kim, Jae Heon Lee, Sang Hun Lee, Eun Jung Park, Serk In Song, Yun Seob https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/77722 2026-03-20T00:01:15Z 2026-04-01T00:00:00Z

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 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 https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79436 2026-03-10T05:00:14Z 2026-03-01T00:00:00Z

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 Kim, Meyoung-Kon Lee, Junghan Kang, A-Ram https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79565 2026-03-24T00:30:45Z 2026-03-01T00:00:00Z

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 Weng, Guangzheng Kim, Hyobin Martin, Patrick Kim, Junil Kim, Tae-Hyung Nam, Gi-Hoon Kim, Dongha Won, Kyoung Jae https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79205 2026-01-26T07:00:24Z 2026-01-01T00:00:00Z

Title: A Generalizable Transformer Framework for Gene Regulatory Network Inference from Single-Cell Transcriptomes Authors: Weng, Guangzheng; Kim, Hyobin; Martin, Patrick; Kim, Junil; Kim, Tae-Hyung; Nam, Gi-Hoon; Kim, Dongha; Won, Kyoung Jae Abstract: Gene regulatory network (GRN) inference has advanced substantially through supervised and unsupervised learning approaches; however, many existing methods require extensive computational resources and exhibit limited generalizability across biological contexts. In addition, they do not fully exploit the growing availability of large-scale transcriptomic and regulatory data. Here, we present FTGRN (Foundation Transformer for Gene Regulatory Networks), a universal framework for GRN inference based on a pretrain-finetune paradigm. FTGRN integrates gene embeddings derived from Generative Pre-trained Transformer-4 (GPT-4) with publicly available chromatin immunoprecipitation sequencing (ChIP-seq) data to construct a regulatory knowledge base for pretraining a Transformer-based graph neural network. The pretrained model is subsequently fine-tuned using single-cell RNA sequencing (scRNA-seq) data to infer context-specific regulatory networks. Leveraging its pretrained foundation, FTGRN enables near real-time GRN inference, generating networks for 2,000 genes in under 30 seconds, substantially outperforming state-of-the-art methods in both speed and predictive accuracy. Application to amino acid-starved mouse embryonic fibroblasts demonstrated that FTGRN accurately reconstructs stress-response GRNs and identifies key regulators, including C/EBP gamma, c-Jun, DDIT4, and c-Fos. Collectively, FTGRN provides a scalable, adaptable, and interpretable framework for GRN inference in single-cell genomics.

2026-01-01T00:00:00Z