Characterization of MSC Growth, Differentiation, and EV Production in CNF Hydrogels Under Static and Dynamic Cultures in Hypoxic and Normoxic Conditions.

IF 3.8 3区 医学 Q2 ENGINEERING, BIOMEDICAL Bioengineering Pub Date : 2024-10-21 DOI:10.3390/bioengineering11101050
Ilias Nikolits, Farhad Chariyev-Prinz, Dominik Egger, Falk Liebner, Nicolas Mytzka, Cornelia Kasper
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Abstract

Mesenchymal stem cells (MSCs) hold immense therapeutic potential due to their regenerative and immunomodulatory properties. However, to utilize this potential, it is crucial to optimize their in vitro cultivation conditions. Three-dimensional (3D) culture methods using cell-laden hydrogels aim to mimic the physiological microenvironment in vitro, thus preserving MSC biological functionalities. Cellulosic hydrogels are particularly promising due to their biocompatibility, sustainability, and tunability in terms of chemical, morphological, and mechanical properties. This study investigated the impact of (1) two physical crosslinking scenarios for hydrogels derived from anionic cellulose nanofibers (to-CNF) used to encapsulate adipose-derived MSCs (adMSCs) and (2) physiological culture conditions on the in vitro proliferation, differentiation, and extracellular vesicle (EV) production of these adMSCs. The results revealed that additional Ca2+-mediated crosslinking, intended to complement the self-assembly and gelation of aqueous to-CNF in the adMSC cultivation medium, adversely affected both the mechanical properties of the hydrogel spheres and the growth of the encapsulated cells. However, cultivation under dynamic and hypoxic conditions significantly improved the proliferation and differentiation of the encapsulated adMSCs. Furthermore, it was demonstrated that the adMSCs in the CNF hydrogel spheres exhibited potential for scalable EV production with potent immunosuppressive capacities in a bioreactor system. These findings underscore the importance of physiological culture conditions and the suitability of cellulosic materials for enhancing the therapeutic potential of MSCs. Overall, this study provides valuable insights for optimizing the in vitro cultivation of MSCs for various applications, including tissue engineering, drug testing, and EV-based therapies.

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低氧和常氧条件下静态和动态培养 CNF 水凝胶中间叶干细胞的生长、分化和 EV 生成特征。
间充质干细胞(MSCs)具有再生和免疫调节特性,具有巨大的治疗潜力。然而,要利用这一潜力,优化其体外培养条件至关重要。使用含有细胞的水凝胶的三维(3D)培养方法旨在模拟体外生理微环境,从而保留间充质干细胞的生物功能。纤维素水凝胶因其生物相容性、可持续性以及在化学、形态和机械性能方面的可调性而特别具有发展前景。本研究调查了(1)阴离子纤维素纳米纤维(to-CNF)衍生的水凝胶的两种物理交联方案对封装脂肪来源间充质干细胞(adMSCs)的影响;(2)生理培养条件对这些adMSCs的体外增殖、分化和细胞外囊泡(EV)生成的影响。结果发现,为了补充 adMSC 培养基中水性 to-CNF 的自组装和凝胶化,额外的 Ca2+ 介导的交联对水凝胶球的机械性能和包裹细胞的生长都有不利影响。然而,在动态和低氧条件下培养则能明显改善包裹的 adMSCs 的增殖和分化。此外,研究还表明,CNF 水凝胶球中的 adMSCs 具有在生物反应器系统中生产具有强效免疫抑制能力的可扩展 EV 的潜力。这些发现强调了生理培养条件的重要性以及纤维素材料对提高间充质干细胞治疗潜力的适用性。总之,这项研究为优化间充质干细胞的体外培养提供了宝贵的见解,可用于组织工程、药物测试和基于 EV 的疗法等各种应用。
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来源期刊
Bioengineering
Bioengineering Chemical Engineering-Bioengineering
CiteScore
4.00
自引率
8.70%
发文量
661
期刊介绍: Aims Bioengineering (ISSN 2306-5354) provides an advanced forum for the science and technology of bioengineering. It publishes original research papers, comprehensive reviews, communications and case reports. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. All aspects of bioengineering are welcomed from theoretical concepts to education and applications. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. There are, in addition, four key features of this Journal: ● We are introducing a new concept in scientific and technical publications “The Translational Case Report in Bioengineering”. It is a descriptive explanatory analysis of a transformative or translational event. Understanding that the goal of bioengineering scholarship is to advance towards a transformative or clinical solution to an identified transformative/clinical need, the translational case report is used to explore causation in order to find underlying principles that may guide other similar transformative/translational undertakings. ● Manuscripts regarding research proposals and research ideas will be particularly welcomed. ● Electronic files and software regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material. ● We also accept manuscripts communicating to a broader audience with regard to research projects financed with public funds. Scope ● Bionics and biological cybernetics: implantology; bio–abio interfaces ● Bioelectronics: wearable electronics; implantable electronics; “more than Moore” electronics; bioelectronics devices ● Bioprocess and biosystems engineering and applications: bioprocess design; biocatalysis; bioseparation and bioreactors; bioinformatics; bioenergy; etc. ● Biomolecular, cellular and tissue engineering and applications: tissue engineering; chromosome engineering; embryo engineering; cellular, molecular and synthetic biology; metabolic engineering; bio-nanotechnology; micro/nano technologies; genetic engineering; transgenic technology ● Biomedical engineering and applications: biomechatronics; biomedical electronics; biomechanics; biomaterials; biomimetics; biomedical diagnostics; biomedical therapy; biomedical devices; sensors and circuits; biomedical imaging and medical information systems; implants and regenerative medicine; neurotechnology; clinical engineering; rehabilitation engineering ● Biochemical engineering and applications: metabolic pathway engineering; modeling and simulation ● Translational bioengineering
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