Romain Schaller, Adrien Moya, Gangyu Zhang, Mansoor Chaaban, Robert Paillaud, Ewelina M Bartoszek, Dirk J Schaefer, Ivan Martin, Alexandre Kaempfen, Arnaud Scherberich
{"title":"为共生畸形儿童设计趾骨移植:概念验证","authors":"Romain Schaller, Adrien Moya, Gangyu Zhang, Mansoor Chaaban, Robert Paillaud, Ewelina M Bartoszek, Dirk J Schaefer, Ivan Martin, Alexandre Kaempfen, Arnaud Scherberich","doi":"10.1177/20417314241257352","DOIUrl":null,"url":null,"abstract":"<p><p>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) <i>in vitro</i> that remodel into bone tissue <i>in vivo</i> via ECO. Second, we developed and optimized an <i>in vitro</i> protocol to generate HCTs in the shape of small phalangeal bones (108-390 mm<sup>3</sup>) using freshly isolated adult cells from the stromal vascular fraction (SVF) of adipose tissue, associated with two commercially available large collagen scaffolds (Zimmer Plug<sup>®</sup> and Optimaix 3D<sup>®</sup>). We showed that after 12 weeks of <i>in vivo</i> 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<sup>6</sup> cells per grafts) in the same <i>in vitro</i> and <i>in vivo</i> 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.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"15 ","pages":"20417314241257352"},"PeriodicalIF":6.7000,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171439/pdf/","citationCount":"0","resultStr":"{\"title\":\"Engineered phalangeal grafts for children with symbrachydactyly: A proof of concept.\",\"authors\":\"Romain Schaller, Adrien Moya, Gangyu Zhang, Mansoor Chaaban, Robert Paillaud, Ewelina M Bartoszek, Dirk J Schaefer, Ivan Martin, Alexandre Kaempfen, Arnaud Scherberich\",\"doi\":\"10.1177/20417314241257352\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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) <i>in vitro</i> that remodel into bone tissue <i>in vivo</i> via ECO. Second, we developed and optimized an <i>in vitro</i> protocol to generate HCTs in the shape of small phalangeal bones (108-390 mm<sup>3</sup>) using freshly isolated adult cells from the stromal vascular fraction (SVF) of adipose tissue, associated with two commercially available large collagen scaffolds (Zimmer Plug<sup>®</sup> and Optimaix 3D<sup>®</sup>). We showed that after 12 weeks of <i>in vivo</i> 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<sup>6</sup> cells per grafts) in the same <i>in vitro</i> and <i>in vivo</i> 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.</p>\",\"PeriodicalId\":17384,\"journal\":{\"name\":\"Journal of Tissue Engineering\",\"volume\":\"15 \",\"pages\":\"20417314241257352\"},\"PeriodicalIF\":6.7000,\"publicationDate\":\"2024-06-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171439/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Tissue Engineering\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://doi.org/10.1177/20417314241257352\",\"RegionNum\":1,\"RegionCategory\":\"工程技术\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"CELL & TISSUE ENGINEERING\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Tissue Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1177/20417314241257352","RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}
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.
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.