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用于治疗肝纤维化的两亲性脂质肽工程化胎盘间充质干细胞

Amphiphilic lipid-peptide engineered placenta-derived mesenchymal stem cells for liver fibrosis treatment.

作者信息

Park Hee Won, Lee Dae Hyun, Kim Sungjun, Park Hyeri, Jangid Ashok Kumar, Lee Chae Eun, Park Jaewon, Park Gyu Tae, Park Ha Yeon, Kim HyunJin, Kim Jae Ho, Kim Gi Jin, Kim Kyobum

机构信息

Department of Chemical & Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea.

Department of Biomedical Science, CHA University, Seongnam-si 13488, Gyeonggi-Do, Republic of Korea.

出版信息

Asian J Pharm Sci. 2025 Aug;20(4):101061. doi: 10.1016/j.ajps.2025.101061. Epub 2025 Apr 22.


DOI:10.1016/j.ajps.2025.101061
PMID:40703618
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12281255/
Abstract

The global mortality rate due to liver diseases, particularly liver fibrosis, is increasing. Among various treatment methods, stem cell therapy using placenta-derived mesenchymal stem cells (PDMSCs) offers distinct benefits, including ease of isolation and superior proliferative potential. To enhance the therapeutic efficacy of PDMSCs, the WKYMVm peptide was selected for cell engineering. Immobilization of WKYMVm on PDMSC membranes facilitates effective peptide binding to the formyl peptide receptor 2 on adjacent PDMSCs and hepatocytes, thereby enhancing cell activation and achieving more efficient peptide utilization compared to bolus peptide treatment. Increased cell activation enhances the secretion of paracrine factors including growth factors and cytokines, which in turn improves liver function and vascular repair in both and models. This approach not only enhances the angiogenic and therapeutic capacities of stem cells, but also enables efficient peptide utilization, minimizing potential side effects and costs associated with high peptide dosages. Overall, our study demonstrates significant promise of stem cell therapy for treating liver fibrosis. Thus, stem cell therapy offers considerable prospects for clinical applications.

摘要

全球因肝脏疾病,尤其是肝纤维化导致的死亡率正在上升。在各种治疗方法中,使用胎盘来源的间充质干细胞(PDMSC)进行干细胞治疗具有显著优势,包括易于分离和出色的增殖潜力。为提高PDMSC的治疗效果,选择WKYMVm肽进行细胞工程改造。将WKYMVm固定在PDMSC膜上有助于该肽与相邻PDMSC和肝细胞上的甲酰肽受体2有效结合,从而增强细胞活化,与推注肽治疗相比,实现更高效的肽利用。细胞活化增加会增强包括生长因子和细胞因子在内的旁分泌因子的分泌,进而改善体内和体外模型中的肝功能和血管修复。这种方法不仅增强了干细胞的血管生成和治疗能力,还能实现肽的高效利用,将与高剂量肽相关的潜在副作用和成本降至最低。总体而言,我们的研究表明干细胞治疗肝纤维化具有巨大潜力。因此,干细胞治疗在临床应用中具有广阔前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/4b61f93f4a60/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/2878702e91c1/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/4b6af9e46c1c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/c36f08e28dcd/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/bc6d4b0f8cc9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/42006b4e0a5b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/880a960baf22/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/0bdd7853db82/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/4b61f93f4a60/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/2878702e91c1/ga1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/4b6af9e46c1c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/c36f08e28dcd/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/bc6d4b0f8cc9/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/42006b4e0a5b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/880a960baf22/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/0bdd7853db82/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef40/12281255/4b61f93f4a60/gr7.jpg

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[1]
Amphiphilic lipid-peptide engineered placenta-derived mesenchymal stem cells for liver fibrosis treatment.

Asian J Pharm Sci. 2025-8

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本文引用的文献

[1]
Smart Microneedle Arrays Integrating Cell-Free Therapy and Nanocatalysis to Treat Liver Fibrosis.

Adv Sci (Weinh). 2024-8

[2]
MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation.

Asian J Pharm Sci. 2024-2

[3]
Optimized Design of Hyaluronic Acid-Lipid Conjugate Biomaterial for Augmenting CD44 Recognition of Surface-Engineered NK Cells.

Biomacromolecules. 2024-3-11

[4]
Surface Engineering of Natural Killer Cells with CD44-targeting Ligands for Augmented Cancer Immunotherapy.

Small. 2024-6

[5]
Ex Vivo Surface Decoration of Phenylboronic Acid onto Natural Killer Cells for Sialic Acid-Mediated Versatile Cancer Cell Targeting.

Biomacromolecules. 2024-1-8

[6]
Tailoring tumor-recognizable hyaluronic acid-lipid conjugates to enhance anticancer efficacies of surface-engineered natural killer cells.

Nano Converg. 2023-12-14

[7]
Increased Hepatocyte Growth Factor Secretion by Placenta-Derived Mesenchymal Stem Cells Improves Ovarian Function in an Ovariectomized Rat Model via Vascular Remodeling by Wnt Signaling Activation.

Cells. 2023-11-25

[8]
Peptide Decoration Strategies on Stem Cell Surfaces for Augmenting Endothelium Interaction.

Tissue Eng Part B Rev. 2024-6

[9]
Hepatic inflammatory responses in liver fibrosis.

Nat Rev Gastroenterol Hepatol. 2023-10

[10]
Treatment of liver fibrosis: Past, current, and future.

World J Hepatol. 2023-6-27

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