为共生畸形儿童设计趾骨移植:概念验证

IF 6.7 1区 工程技术 Q1 CELL & TISSUE ENGINEERING
Journal of Tissue Engineering Pub Date : 2024-06-12 eCollection Date: 2024-01-01 DOI:10.1177/20417314241257352
Romain Schaller, Adrien Moya, Gangyu Zhang, Mansoor Chaaban, Robert Paillaud, Ewelina M Bartoszek, Dirk J Schaefer, Ivan Martin, Alexandre Kaempfen, Arnaud Scherberich
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引用次数: 0

摘要

组织工程方法在再生医学领域大有可为,尤其是在儿科应用中,理想的移植物需要恢复目标组织的功能并考虑生长。在本研究中,我们旨在为患有共生畸形的儿童制定一个方案,设计出大小合适的自体指骨移植物。这种情况会导致双手手指短小和缺骨。我们采用了一种先前描述过的、基于软骨内骨化(ECO)--导致骨骼和骨髓发育的主要途径--的发育启发策略,并将脂肪衍生基质细胞(ASCs)作为软骨原生细胞的来源。首先,我们证明了与胶原海绵相关的小儿 ASCs 可在体外生成肥大软骨组织(HCTs),并在体内通过 ECO 重塑为骨组织。其次,我们开发并优化了一种体外方案,利用从脂肪组织基质血管部分(SVF)新鲜分离的成体细胞,结合两种市售的大型胶原支架(Zimmer Plug® 和 Optimaix 3D® ),生成小趾骨形状的 HCT(108-390 立方毫米)。我们的研究表明,在免疫力低下的小鼠模型中体内植入 12 周后,这些增大的移植物重塑成了骨器官(包括骨髓组织),并保持了确定的形状和大小。最后,我们在相同的体外和体内环境中使用最小扩增的儿科 ASCs(每移植物 3 × 106 个细胞),复制了类似的结果(尽管软骨和骨形成略有减少),从而验证了我们的儿科趾骨工程策略与临床相关情况的兼容性。综上所述,这些结果证明了一种自体方法的概念,即在先天性共济失调患儿中使用ASCs生成具有相关临床尺寸的成骨性趾骨移植物,尽管可从儿科患者中获得的组织数量有限。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Engineered phalangeal grafts for children with symbrachydactyly: A proof of concept.

Tissue engineering approaches hold great promise in the field of regenerative medicine, especially in the context of pediatric applications, where ideal grafts need to restore the function of the targeted tissue and consider growth. In the present study, we aimed to develop a protocol to engineer autologous phalangeal grafts of relevant size for children suffering from symbrachydactyly. This condition results in hands with short fingers and missing bones. A previously-described, developmentally-inspired strategy based on endochondral ossification (ECO)-the main pathway leading to bone and bone marrow development-and adipose derived-stromal cells (ASCs) as the source of chondroprogenitor was used. First, we demonstrated that pediatric ASCs associated with collagen sponges can generate hypertrophic cartilage tissues (HCTs) in vitro that remodel into bone tissue in vivo via ECO. Second, we developed and optimized an in vitro protocol to generate HCTs in the shape of small phalangeal bones (108-390 mm3) using freshly isolated adult cells from the stromal vascular fraction (SVF) of adipose tissue, associated with two commercially available large collagen scaffolds (Zimmer Plug® and Optimaix 3D®). We showed that after 12 weeks of in vivo implantation in an immunocompromised mouse model such upscaled grafts remodeled into bone organs (including bone marrow tissues) retaining the defined shape and size. Finally, we replicated similar outcome (albeit with a slight reduction in cartilage and bone formation) by using minimally expanded pediatric ASCs (3 × 106 cells per grafts) in the same in vitro and in vivo settings, thereby validating the compatibility of our pediatric phalanx engineering strategy with a clinically relevant scenario. Taken together, these results represent a proof of concept of an autologous approach to generate osteogenic phalangeal grafts of pertinent clinical size, using ASCs in children born with symbrachydactyly, despite a limited amount of tissue available from pediatric patients.

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来源期刊
Journal of Tissue Engineering
Journal of Tissue Engineering Engineering-Biomedical Engineering
CiteScore
11.60
自引率
4.90%
发文量
52
审稿时长
12 weeks
期刊介绍: The Journal of Tissue Engineering (JTE) is a peer-reviewed, open-access journal dedicated to scientific research in the field of tissue engineering and its clinical applications. Our journal encompasses a wide range of interests, from the fundamental aspects of stem cells and progenitor cells, including their expansion to viable numbers, to an in-depth understanding of their differentiation processes. Join us in exploring the latest advancements in tissue engineering and its clinical translation.
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