Istituto Nanoscienze-CNR, Euromediterranean Center for Nanomaterial Modelling and Technology (ECMT), via Arnesano, 73100 Lecce, Italy; Center for Biomolecular Nanotechnologies @UNILE, Istituto Italiano di Tecnologia, via Barsanti, 73010 Arnesano, Lecce, Italy.
Istituto Nanoscienze-CNR, Euromediterranean Center for Nanomaterial Modelling and Technology (ECMT), via Arnesano, 73100 Lecce, Italy; Dipartimento di Matematica e Fisica "Ennio De Giorgi", Università del Salento, via Arnesano, 73100 Lecce, Italy.
Biomaterials. 2016 Jul;94:57-69. doi: 10.1016/j.biomaterials.2016.03.042. Epub 2016 Mar 31.
The treatment of renal injury by autologous, patient-specific adult stem cells is still an unmet need. Unsolved issues remain the spatial integration of stem cells into damaged areas of the organ, the commitment in the required cell type and the development of improved bioengineered devices. In this respect, biomaterials and architectures have to be specialized to control stem cell differentiation. Here, we perform an extensive study on micropatterned extracellular matrix proteins, which constitute a simple and non-invasive approach to drive the differentiation of adult renal progenitor/stem cells (ARPCs) from human donors. ARPCs are interfaced with fibronectin (FN) micropatterns, in the absence of exogenous chemicals or cellular reprogramming. We obtain the differentiation towards tubular cells of ARPCs cultured in basal medium conditions, the tubular commitment thus being specifically induced by micropatterned substrates. We characterize the stability of the tubular differentiation as well as the induction of a polarized phenotype in micropatterned ARPCs. Thus, the developed cues, driving the functional commitment of ARPCs, offer a route to recreate the microenvironment of the stem cell niche in vitro, that may serve, in perspective, for the development of ARPC-based bioengineered devices.
自体、患者特异性成体干细胞治疗肾损伤仍然是一个未满足的需求。未解决的问题仍然是干细胞在器官损伤区域的空间整合、向所需细胞类型的分化以及改进的生物工程设备的开发。在这方面,生物材料和架构必须专门用于控制干细胞分化。在这里,我们对细胞外基质蛋白的微图案进行了广泛的研究,这是一种简单且非侵入性的方法,可以驱动来自人类供体的成体肾祖细胞/干细胞(ARPC)的分化。ARPC 与纤连蛋白(FN)微图案相互作用,而无需外源性化学物质或细胞重编程。我们在基础培养基条件下培养 ARPC,使其分化为管状细胞,因此管状细胞的分化是由微图案基底特异性诱导的。我们对微图案 ARPC 中管状分化的稳定性以及极化表型的诱导进行了表征。因此,这些诱导分化的信号可以促使 ARPC 进行功能分化,为在体外重建干细胞龛的微环境提供了一种途径,这可能有助于开发基于 ARPC 的生物工程设备。