脾脏
细胞外基质
再生(生物学)
细胞生物学
转化生长因子
肝再生
透明质酸
肝移植
生长因子
移植
转化生长因子β
化学
癌症研究
生物
免疫学
医学
生物化学
内科学
解剖
受体
作者
Zhenzhen Wang,Daping Xie,Jiayi Li,Ziyu Zhai,Zhuojian Lu,Xuejiao Tian,Yiming Niu,Qi Zhao,Peng Zheng,Lei Dong,Chunming Wang
标识
DOI:10.1016/j.jhep.2024.01.005
摘要
Abstract
Background & Aims
Ectopic liver regeneration in the spleen is a promising alternative to organ transplantation for treating liver failure. To accommodate transplanted liver cells, the splenic tissue must undergo structural changes to increase extracellular matrix (ECM) content, demanding a safe, efficient approach for tissue remodelling. Methods
We synthesised sulphated hyaluronic acid (sHA) with an affinity for the latent complex of TGF-β and cross-linked it into a gel network (sHA-X) via click chemistry. We injected this glycan to remodel the splenic tissue by activating endogenous transforming growth factor-beta (TGF-β) to a supraphysiological level. Results
sHA-X efficiently bound to the abundant latent TGF-β in the spleen. It provided the molecular force to liberate the active TGF-β dimers from their latent complex, mimicking the ‘bind-and-pull' mechanism required for physiological activation of TGF-β and reshaping the splenic tissue to support liver cell growth. Strikingly, hepatocytes transplanted to the remodelled spleen developed into the liver tissue with sufficient volume to exert potent functions for rescuing the animals with 90% hepatectomy and metabolic liver disorder (in Fah-/- transgenic model), with no adverse effects observed and no additional drugs required. Conclusion
; Our findings highlight the efficacy and translational potential of sHA-X to remodel a specific organ by mechanically activating one single cytokine, representing a novel strategy for designing biomaterials-based therapies for organ regeneration.
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