Alipio Amaziah R, Vieira Melissa R, Haefeli Tamara, Hoelting Lisa, Frey Olivier, El Haj Alicia J, Arno Maria C
School of Chemistry, University of Birmingham, Edgbaston, Birmingham, UK.
Healthcare Technologies Institute, Institute of Translational Medicine, University of Birmingham, Edgbaston, Birmingham, UK.
Commun Biol. 2025 Jul 10;8(1):1023. doi: 10.1038/s42003-025-08408-x.
The burgeoning field of cell therapies is rapidly expanding, offering the promise to tackle complex and unsolved healthcare problems. One prominent example is represented by CAR T-cells, which have been introduced into the clinic for treating a variety of cancers. Promising cell therapeutics have also been developed to promote tissue regeneration, showing high potencies for the treatment of damaged liver. Nevertheless, in the remit of regenerative medicine, cell-therapy efficacies remain suboptimal as a consequence of the low engraftment of injected cells to the existing surrounding tissue. Herein, we present a facile approach to enhance the adhesion and engraftment of therapeutic hepatic progenitor cells (HPCs) through specific and homogeneous cell surface modification with exogenous polysaccharides, without requiring genetic modification. Coated HPCs exhibit significantly increased markers of adhesion and cell spreading and demonstrate preferential interactions with certain extra-cellular matrix proteins. Moreover, they display enhanced binding to endothelial cells and 3D liver microtissues. This translatable methodology shows promise for improving therapeutic cell engraftment, offering a potential alternative to liver transplantation in end-stage liver disease.
细胞疗法这一新兴领域正在迅速扩展,有望解决复杂且尚未解决的医疗保健问题。嵌合抗原受体(CAR)T细胞就是一个突出的例子,它已被引入临床用于治疗多种癌症。人们还开发出了有前景的细胞疗法来促进组织再生,显示出对受损肝脏的治疗具有高效能。然而,在再生医学领域,由于注入的细胞在现有周围组织中的低植入率,细胞疗法的疗效仍然不尽人意。在此,我们提出一种简便的方法,通过用外源性多糖进行特异性和均匀的细胞表面修饰来增强治疗性肝祖细胞(HPC)的黏附与植入,而无需进行基因改造。包被的HPC表现出显著增加的黏附标记和细胞铺展,并证明与某些细胞外基质蛋白存在优先相互作用。此外,它们与内皮细胞和三维肝脏微组织的结合增强。这种可转化的方法显示出改善治疗性细胞植入的前景,为终末期肝病的肝移植提供了一种潜在的替代方案。