骨痂类器官揭示了不同供体间软骨到骨的转变机制和生物性别的作用

IF 14.3 1区 医学 Q1 CELL & TISSUE ENGINEERING
Isaak Decoene, Hanna Svitina, Mohamed Belal Hamed, Anastassios Economou, Steve Stegen, Frank P. Luyten, Ioannis Papantoniou
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引用次数: 0

摘要

组织工程先进治疗药物产品的临床翻译受到缺乏患者依赖和独立的过程中生物质量控制的阻碍,这些控制反映了体内结果。最近对天然骨修复机制的研究强调了一种强大的路径依赖性。基于类器官的自下而上发育工程模仿了这种路径依赖性,设计出个性化的无支架活体植入物,具有内置结果可预测性。然而,缺乏足够的(非侵入性的)工程组织质量指标。此外,对供体变异和生物性别作为骨修复机制影响因素的作用认识不足,阻碍了个性化骨植入物方案的实施。本研究将男性和女性骨形成类器官与非骨形成类器官的细胞外基质组成、转录组和分泌的蛋白质组特征进行了比较,以直接将体内结果与质量指标联系起来。结果,骨形成的骨痂类器官的供体变异指向两种不同的成骨途径,要么通过肥大软骨,要么通过纤维软骨模板。随后的途径是确定的早期,作为一个生物性别依赖的激活不同的祖先群体。与供体或生物性别无关,软骨到骨的转变是由一组共同的分泌因子驱动的,这些因子在细胞外基质重塑、矿化和脉管系统的吸引中发挥作用。因此,分泌的蛋白质组是报告生物效力的非侵入性生物标志物的来源,可能是基于类器官的骨组织工程中数据驱动决策的缺失环节。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Callus organoids reveal distinct cartilage to bone transition mechanisms across donors and a role for biological sex

Callus organoids reveal distinct cartilage to bone transition mechanisms across donors and a role for biological sex

Clinical translation of tissue-engineered advanced therapeutic medicinal products is hindered by a lack of patient-dependent and independent in-process biological quality controls that are reflective of in vivo outcomes. Recent insights into the mechanism of native bone repair highlight a robust path dependence. Organoid-based bottom-up developmental engineering mimics this path-dependence to design personalized living implants scaffold-free, with in-build outcome predictability. Yet, adequate (noninvasive) quality metrics of engineered tissues are lacking. Moreover, insufficient insight into the role of donor variability and biological sex as influencing factors for the mechanism toward bone repair hinders the implementation of such protocols for personalized bone implants. Here, male and female bone-forming organoids were compared to non-bone-forming organoids regarding their extracellular matrix composition, transcriptome, and secreted proteome signatures to directly link in vivo outcomes to quality metrics. As a result, donor variability in bone-forming callus organoids pointed towards two distinct pathways to bone, through either a hypertrophic cartilage or a fibrocartilaginous template. The followed pathway was determined early, as a biological sex-dependent activation of distinct progenitor populations. Independent of donor or biological sex, a cartilage-to-bone transition was driven by a common panel of secreted factors that played a role in extracellular matrix remodeling, mineralization, and attraction of vasculature. Hence, the secreted proteome is a source of noninvasive biomarkers that report on biological potency and could be the missing link toward data-driven decision-making in organoid-based bone tissue engineering.

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来源期刊
Bone Research
Bone Research CELL & TISSUE ENGINEERING-
CiteScore
20.00
自引率
4.70%
发文量
289
审稿时长
20 weeks
期刊介绍: Established in 2013, Bone Research is a newly-founded English-language periodical that centers on the basic and clinical facets of bone biology, pathophysiology, and regeneration. It is dedicated to championing key findings emerging from both basic investigations and clinical research concerning bone-related topics. The journal's objective is to globally disseminate research in bone-related physiology, pathology, diseases, and treatment, contributing to the advancement of knowledge in this field.
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