Schaller Romain, Moya Adrien, Zhang Gangyu, Chaaban Mansoor, Paillaud Robert, Bartoszek Ewelina M, Schaefer Dirk J, Martin Ivan, Kaempfen Alexandre, Scherberich Arnaud
Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland.
Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, University Hospital Basel, Basel, Switzerland.
J Tissue Eng. 2024 Jun 12;15:20417314241257352. doi: 10.1177/20417314241257352. eCollection 2024 Jan-Dec.
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) that remodel into bone tissue via ECO. Second, we developed and optimized an protocol to generate HCTs in the shape of small phalangeal bones (108-390 mm) 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 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 × 10 cells per grafts) in the same and 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.
组织工程方法在再生医学领域具有巨大潜力，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因素。在本研究中，我们旨在开发一种方案，为患有短指畸形的儿童构建具有相关尺寸的自体指骨移植物。这种病症会导致手部手指短小且骨骼缺失。我们采用了一种先前描述的、受发育启发的策略，该策略基于软骨内成骨（ECO）——导致骨骼和骨髓发育的主要途径——以及脂肪来源的基质细胞（ASCs）作为软骨祖细胞的来源。首先，我们证明了与胶原海绵相关的儿科ASCs能够生成肥大软骨组织（HCTs），这些组织可通过ECO重塑为骨组织。其次，我们开发并优化了一种方案，使用从脂肪组织的基质血管部分（SVF）新鲜分离的成体细胞，与两种市售的大型胶原支架（Zimmer Plug和Optimaix 3D）相结合，生成小指骨形状（108 - 390毫米）的HCTs。我们表明，在免疫受损小鼠模型中植入12周后，这种放大的移植物会重塑为骨器官（包括骨髓组织），并保留确定的形状和尺寸。最后，我们在相同的设置下使用极少传代的儿科ASCs（每个移植物3×10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指骨工程策略与临床相关情况的兼容性。综上所述，这些结果代表了一种自体方法的概念验证，即使用患有短指畸形儿童的ASCs生成具有相关临床尺寸的成骨指骨移植物，尽管儿科患者可用的组织量有限。
Zotero 插件
