{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:48:12Z","timestamp":1753890492025,"version":"3.41.2"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006087","name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico Universidad Nacional Aut\u00f3noma de M\u00e9xico","doi-asserted-by":"publisher","award":["IN211117 IN213314"],"award-info":[{"award-number":["IN211117 IN213314"]}],"id":[{"id":"10.13039\/501100006087","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","award":["1887"],"award-info":[{"award-number":["1887"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Organ formation initiates once cells become committed to one of the three embryonic germ layers. In the early stages of embryogenesis, different gene transcription networks regulate cell fate after each germ layer is established, thereby directing the formation of complex tissues and functional organs. These events can be modeled <jats:italic>in vitro<\/jats:italic> by creating organoids from induced pluripotent, embryonic, or adult stem cells to study organ formation. Under these conditions, the induced cells are guided down the developmental pathways as in embryonic development, resulting in an organ of a smaller size that possesses the essential functions of the organ of interest. Although organoids are widely studied, the formation of skeletal elements in an organoid model has not yet been possible. Therefore, we suggest that the formation of skeletal elements using the recombinant limb (RL) assay system can serve as an <jats:italic>in vivo<\/jats:italic> organoid model. RLs are formed from undissociated or dissociated-reaggregated undifferentiated mesodermal cells introduced into an ectodermal cover obtained from an early limb bud. Next, this filled ectoderm is grafted into the back of a donor chick embryo. Under these conditions, the cells can receive the nascent embryonic signals and develop complex skeletal elements. We propose that the formation of skeletal elements induced through the RL system may occur from stem cells or other types of progenitors, thus enabling the study of morphogenetic properties <jats:italic>in vivo<\/jats:italic> from these cells for the first time.<\/jats:p>","DOI":"10.3389\/fcell.2022.863140","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T05:50:44Z","timestamp":1650952244000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Recombinant Limb Assay as in Vivo Organoid Model"],"prefix":"10.3389","volume":"10","author":[{"given":"Roberto Dami\u00e1n","family":"Garc\u00eda-Garc\u00eda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estefan\u00eda","family":"Garay-Pacheco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica Cristina","family":"Mar\u00edn-Llera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jes\u00fas","family":"Chimal-Monroy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"145","DOI":"10.2174\/1871529X19666190719105954","article-title":"Impact of Leukemia Stem Cells Phenotype Expression on Response to Induction Therapy in Acute Myeloid Leukemia Patients","volume":"20","author":"Almohsen","year":"2020","journal-title":"Chddt"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(77)90110-5","article-title":"Stage-Related Capacity for Limb Chondrogenesis in Cell Culture","volume":"60","author":"Ahrens","year":"1977","journal-title":"Dev. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1111\/j.1600-0765.1996.tb00476.x","article-title":"Human Cementum Protein Extract Promotes Chondrogenesis and Mineralization in Mesenchymal Cells","volume":"31","author":"Arzate","year":"1996","journal-title":"J. Periodontal Res."},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1101\/2021.10.01.462632","article-title":"Direct Reprogramming of Non-limb Fibroblasts to Cells with Properties of Limb Progenitors","author":"Atsuta","year":"2021","journal-title":"bioRxiv"},{"key":"B4","doi-asserted-by":"publisher","first-page":"74","DOI":"10.3324\/haematol.2019.238261","article-title":"Expanded Circulating Hematopoietic Stem\/progenitor Cells as Novel Cell Source for the Treatment of TCIRG1 Osteopetrosis","volume":"106","author":"Capo","year":"2020","journal-title":"haematol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"R1024","DOI":"10.1016\/j.cub.2017.07.010","article-title":"Coordination of Morphogenesis and Cell-Fate Specification in Development","volume":"27","author":"Chan","year":"2017","journal-title":"Curr. Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1126\/science.1199499","article-title":"Initiation of Proximal-Distal Patterning in the Vertebrate Limb by Signals and Growth","volume":"332","author":"Cooper","year":"2011","journal-title":"Science"},{"key":"B7","doi-asserted-by":"publisher","first-page":"C151","DOI":"10.1152\/ajpcell.00120.2020","article-title":"A Brief History of Organoids","volume":"319","author":"Corr\u00f2","year":"2020","journal-title":"Am. J. Physiology-Cell Physiol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/0012-1606(75)90084-6","article-title":"Inhibitory Effect on Limb Morphogenesis by Cells of the Polarizing Zone Coaggregated with Pre- or Postaxial wing Bud Mesoderm","volume":"46","author":"Crosby","year":"1975","journal-title":"Dev. Biol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/nmeth.4576","article-title":"Organoids","volume":"15","author":"de Souza","year":"2018","journal-title":"Nat. Methods"},{"key":"B10","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1038\/342767a0","article-title":"Coordinate Expression of the Murine Hox-5 Complex Homoeobox-Containing Genes during Limb Pattern Formation","volume":"342","author":"Doll\u00e9","year":"1989","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"05098","DOI":"10.7554\/eLife.05098","article-title":"In Vitro generation of Human Pluripotent Stem Cell Derived Lung Organoids","volume":"4","author":"Dye","year":"2015","journal-title":"eLife"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1093\/jnci\/16.6.1375","article-title":"The Growth of Cells on a Transparent Gel of Reconstituted Rat-Tail Collagen2","volume":"16","author":"Ehrmann","year":"1956","journal-title":"JNCI"},{"key":"B13","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/nature09941","article-title":"Self-organizing Optic-Cup Morphogenesis in Three-Dimensional Culture","volume":"472","author":"Eiraku","year":"2011","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.stem.2008.09.002","article-title":"Self-Organized Formation of Polarized Cortical Tissues from ESCs and its Active Manipulation by Extrinsic Signals","volume":"3","author":"Eiraku","year":"2008","journal-title":"Cell Stem Cell"},{"key":"B16","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/0014-4827(92)90161-z","article-title":"Somatic and Germ Cell Interactions during Histogenetic Aggregation of Mouse Fetal Testes","volume":"198","author":"Escalante-Alcalde","year":"1992","journal-title":"Exp. Cel. Res."},{"key":"B83","first-page":"A53","article-title":"Interactions Between Chick Limb Bud Mesoderm and Reptile Ectoderm Result In Limb Outgrowth in the Limbless Mutant","author":"Fallon","year":"1984","journal-title":"Anatomical Records"},{"key":"B17","doi-asserted-by":"publisher","first-page":"767","DOI":"10.1042\/bj0230767","article-title":"The Growth, Development and Phosphatase Activity of Embryonic Avian Femora and Limb-Buds Cultivated In Vitro","volume":"23","author":"Fell","year":"1929","journal-title":"Biochem. J."},{"key":"B18","doi-asserted-by":"publisher","first-page":"312","DOI":"10.3390\/biom10020312","article-title":"The Role of Retinoic Acid in Establishing the Early Limb Bud","volume":"10","author":"Feneck","year":"2020","journal-title":"Biomolecules"},{"key":"B19","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s004410051273","article-title":"The Recombinant Limb as a Model for the Study of Limb Patterning, and its Application to Muscle Development","volume":"296","author":"Fernandez-Teran","year":"1999","journal-title":"Cel Tissue Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1242\/dev.67.1.13","article-title":"The Proportion and Distribution of Polarizing Zone Cells Causing Morphogenetic Inhibition when Coaggregated with Anterior Half wing Mesoderm in Recombinant Limbs","volume":"67","author":"Frederick","year":"1982","journal-title":"J. Embryol. Exp. Morphol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2928","DOI":"10.1016\/j.devcel.2021.10.009","article-title":"Controlling Tissue Patterning by Translational Regulation of Signaling Transcripts through the Core Translation Factor eIF3c","volume":"56","author":"Fujii","year":"2021","journal-title":"Dev. Cel"},{"key":"B22","doi-asserted-by":"publisher","first-page":"dev200182","DOI":"10.1242\/dev.200182","article-title":"SMAD4 Target Genes Are Part of a Transcriptional Network that Integrates the Response to BMP and SHH Signaling during Early Limb Bud Patterning","volume":"148","author":"Gamart","year":"2021","journal-title":"Development"},{"key":"B23","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1002\/jcb.24388","article-title":"Efficient Differentiation of Human iPSC-Derived Mesenchymal Stem Cells to Chondroprogenitor Cells","volume":"114","author":"Guzzo","year":"2013","journal-title":"J. Cel. Biochem."},{"key":"B24","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/BF01002713","article-title":"Intracellular and Extracellular Control of the Differentiation of Cartilage and Bone","volume":"13","author":"Hall","year":"1981","journal-title":"Histochem. J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1002\/aja.1001950404","article-title":"A Series of normal Stages in the Development of the Chick Embryo","volume":"195","author":"Hamburger","year":"1992","journal-title":"Dev. Dyn."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e1004468","DOI":"10.1371\/journal.pgen.1004468","article-title":"Sp6 and Sp8 Transcription Factors Control AER Formation and Dorsal-Ventral Patterning in Limb Development","volume":"10","author":"Haro","year":"2014","journal-title":"Plos Genet."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1016\/j.stem.2021.05.007","article-title":"Lgr6 marks Epidermal Stem Cells with a Nerve-dependent Role in Wound Re-epithelialization","volume":"28","author":"Huang","year":"2021","journal-title":"Cell Stem Cell"},{"key":"B28","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1016\/j.cell.2014.11.050","article-title":"Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver","volume":"160","author":"Huch","year":"2015","journal-title":"Cell"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1588","DOI":"10.1016\/j.stemcr.2017.10.011","article-title":"miRNome Profiling of Purified Endoderm and Mesoderm Differentiated from hESCs Reveals Functions of miR-483-3p and miR-1263 for Cell-Fate Decisions","volume":"9","author":"Ishikawa","year":"2017","journal-title":"Stem Cel Rep."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17417-9","article-title":"Identification of Osteogenic Progenitor Cell-Targeted Peptides that Augment Bone Formation","volume":"11","author":"Jiang","year":"2020","journal-title":"Nat. Commun."},{"key":"B31","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/nature09726","article-title":"Intrinsic Transition of Embryonic Stem-Cell Differentiation into Neural Progenitors","volume":"470","author":"Kamiya","year":"2011","journal-title":"Nature"},{"key":"B79","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1016\/j.semcancer.2005.05.004","article-title":"Matrigel: Basement Membrane Matrix with Biological Activity","volume":"15","author":"Kleinman","year":"2005","journal-title":"Semin. Cancer Biol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1242\/dev.124.1.133","article-title":"Limb Deformity Proteins: Role in Mesodermal Induction of the Apical Ectodermal ridge","volume":"124","author":"Kuhlman","year":"1997","journal-title":"Development"},{"key":"B33","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3390\/jdb9040047","article-title":"The Organizer and its Signaling in Embryonic Development","volume":"9","author":"Kumar","year":"2021","journal-title":"Jdb"},{"key":"B34","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/nature12517","article-title":"Cerebral Organoids Model Human Brain Development and Microcephaly","volume":"501","author":"Lancaster","year":"2013","journal-title":"Nature"},{"key":"B35","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.cell.2016.06.011","article-title":"Mapping the Pairwise Choices Leading from Pluripotency to Human Bone, Heart, and Other Mesoderm Cell Types","volume":"166","author":"Loh","year":"2016","journal-title":"Cell"},{"key":"B36","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1038\/382360a0","article-title":"The Mouse Engrailed-1 Gene and Ventral Limb Patterning","volume":"382","author":"Loomis","year":"1996","journal-title":"Nature"},{"key":"B37","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1186\/1471-213X-10-69","article-title":"Tgf\u03b22 and 3 Are Coexpressed with Their Extracellular Regulator Ltbp1in the Early Limb Bud and Modulate Mesodermal Outgrowth and BMP Signaling in Chicken Embryos","volume":"10","author":"Lorda-Diez","year":"2010","journal-title":"BMC Dev. Biol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/0012-1606(73)90269-8","article-title":"The Control of the Anteroposterior and Dorsoventral Axes in Embryonic Chick Limbs Constructed of Dissociated and Reaggregated Limb-Bud Mesoderm","volume":"31","author":"MacCabe","year":"1973","journal-title":"Dev. Biol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"e63183","DOI":"10.3791\/63183","article-title":"Chicken Recombinant Limbs Assay to Understand Morphogenesis, Patterning, and Early Steps in Cell Differentiation","author":"Mar\u00edn-Llera","year":"2022","journal-title":"JoVE"},{"key":"B40","doi-asserted-by":"publisher","first-page":"977","DOI":"10.3389\/fgene.2019.00977","article-title":"Understanding the Cellular and Molecular Mechanisms that Control Early Cell Fate Decisions during Appendicular Skeletogenesis","volume":"10","author":"Mar\u00edn-Llera","year":"2019","journal-title":"Front. Genet."},{"key":"B41","doi-asserted-by":"publisher","first-page":"656999","DOI":"10.3389\/fcell.2021.656999","article-title":"SCA-1\/Ly6A Mesodermal Skeletal Progenitor Subpopulations Reveal Differential Commitment of Early Limb Bud Cells","volume":"9","author":"Mar\u00edn-Llera","year":"2021","journal-title":"Front. Cel Dev. Biol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/nature13863","article-title":"Modelling Human Development and Disease in Pluripotent Stem-Cell-Derived Gastric Organoids","volume":"516","author":"McCracken","year":"2014","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","first-page":"dev177956","DOI":"10.1242\/dev.177956","article-title":"Establishing the Pattern of the Vertebrate Limb","volume":"147","author":"McQueen","year":"2020","journal-title":"Development"},{"key":"B44","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1007\/s11626-999-0070-0","article-title":"High Density Micromass Cultures of Embryonic Limb Bud Mesenchymal Cells: An In Vitro Model of Endochondral Skeletal Development","volume":"35","author":"Mello","year":"1999","journal-title":"In Vitro"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1126\/science.1164073","article-title":"Morphogenetic Cell Movements: Diversity from Modular Mechanical Properties","volume":"322","author":"Montell","year":"2008","journal-title":"Science"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11702-y","article-title":"Self-organized Formation of Developing Appendages from Murine Pluripotent Stem Cells","volume":"10","author":"Mori","year":"2019","journal-title":"Nat. Commun."},{"key":"B47","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1016\/j.cell.2008.02.008","article-title":"Differentiation of Embryonic Stem Cells to Clinically Relevant Populations: Lessons from Embryonic Development","volume":"132","author":"Murry","year":"2008","journal-title":"Cell"},{"key":"B48","doi-asserted-by":"publisher","first-page":"2235","DOI":"10.1242\/dev.124.11.2235","article-title":"The Mesenchymal Factor, FGF10, Initiates and Maintains the Outgrowth of the Chick Limb Bud through Interaction with FGF8, an Apical Ectodermal Factor","volume":"124","author":"Ohuchi","year":"1997","journal-title":"Development"},{"key":"B49","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/nprot.2009.51","article-title":"Stepwise Differentiation of Pluripotent Stem Cells into Retinal Cells","volume":"4","author":"Osakada","year":"2009","journal-title":"Nat. Protoc."},{"key":"B15","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/S0925-4773(99)00247-6","article-title":"Pattern Formation and Regulation of Gene Expressions in Chick Recombinant Limbs","volume":"90","author":"Piedra","year":"2000","journal-title":"Mech. Dev."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1401","DOI":"10.1016\/0092-8674(93)90626-2","article-title":"Sonic Hedgehog Mediates the Polarizing Activity of the ZPA","volume":"75","author":"Riddle","year":"1993","journal-title":"Cell"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1089\/hum.2018.124","article-title":"Advances in Gene Therapy for Fanconi Anemia","volume":"29","author":"R\u00edo","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"B52","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1006\/dbio.1994.1296","article-title":"Recombinant Limbs as a Model to Study Homeobox Gene Regulation during Limb Development","volume":"166","author":"Ros","year":"1994","journal-title":"Dev. Biol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1385\/1-59259-066-7:245","article-title":"Methods for Manipulating the Chick Limb Bud to Study Gene Expression, Tissue Interactions, and Patterning","volume":"137","author":"Ros","year":"2000","journal-title":"Methods Mol. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1242\/dev.106831","article-title":"Diffusible Signals and Epigenetic Timing Cooperate in Late Proximo-Distal Limb Patterning","volume":"141","author":"Rosell\u00f3-D\u00edez","year":"2014","journal-title":"Development (Cambridge)"},{"key":"B54","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1126\/science.1199489","article-title":"Diffusible Signals, Not Autonomous Mechanisms, Determine the Main Proximodistal Limb Subdivision","volume":"332","author":"Rosell\u00f3-D\u00edez","year":"2011","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/s41576-018-0051-9","article-title":"Progress and Potential in Organoid Research","volume":"19","author":"Rossi","year":"2018","journal-title":"Nat. Rev. Genet."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1002\/dvdy.308","article-title":"Limb Positioning and Initiation: An Evolutionary Context of Pattern and Formation","volume":"250","author":"Royle","year":"2021","journal-title":"Dev. Dyn."},{"key":"B57","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/nature11859","article-title":"Cytosystems Dynamics in Self-Organization of Tissue Architecture","volume":"493","author":"Sasai","year":"2013","journal-title":"Nature"},{"key":"B58","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 Stem Cells Build Crypt-Villus Structures In Vitro without a Mesenchymal Niche","volume":"459","author":"Sato","year":"2009","journal-title":"Nature"},{"key":"B59","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1002\/9780470514221.ch11","article-title":"Epithelial-Mesenchymal Interactions in Murine Organogenesis","volume":"165","author":"Sax\u00e9n","year":"2007","journal-title":"Postimplantation Dev. Mouse"},{"key":"B60","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1016\/j.ydbio.2005.12.023","article-title":"Expression and Regulation of Antioxidant Enzymes in the Developing Limb Support a Function of ROS in Interdigital Cell Death","volume":"291","author":"Schnabel","year":"2006","journal-title":"Dev. Biol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1016\/j.stem.2021.08.010","article-title":"Tracing the Skeletal Progenitor Transition during Postnatal Bone Formation","volume":"28","author":"Shu","year":"2021","journal-title":"Cell Stem Cell"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1498","DOI":"10.1126\/science.1162782","article-title":"Origin of Stem Cells in Organogenesis","volume":"322","author":"Slack","year":"2008","journal-title":"Science"},{"key":"B63","doi-asserted-by":"publisher","first-page":"91","DOI":"10.22203\/eCM.v026a07","article-title":"A New Take on an Old story: Chick Limb Organ Culture for Skeletal Niche Development and Regenerative Medicine Evaluation","volume":"26","author":"Smith","year":"2013","journal-title":"eCM"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1101\/gad.263003","article-title":"Genetic Interaction between Wnt\/\u03b2-Catenin and BMP Receptor Signaling during Formation of the AER and the Dorsal-Ventral axis in the Limb","volume":"17","author":"Soshnikova","year":"2003","journal-title":"Genes Dev."},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-022-09951-2","article-title":"Methods for Vascularization and Perfusion of Tissue Organoids","author":"Strobel","year":"2022","journal-title":"Mamm. Genome"},{"key":"B66","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2007.11.019","article-title":"Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors","volume":"131","author":"Takahashi","year":"2007","journal-title":"Cell"},{"key":"B67","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"B68","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/0012-1606(81)90370-5","article-title":"In Vitro development of Testis and Ovary from Indifferent Fetal Mouse Gonads","volume":"84","author":"Taketo","year":"1981","journal-title":"Dev. Biol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"3247","DOI":"10.1242\/dev.023176","article-title":"Wnt and FGF Signals Interact to Coordinate Growth with Cell Fate Specification During Limb Development","author":"ten Berge","year":"2008","journal-title":"Development,"},{"key":"B69","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.semcdb.2016.11.008","article-title":"MSC Exosome as a Cell-free MSC Therapy for Cartilage Regeneration: Implications for Osteoarthritis Treatment","volume":"67","author":"Toh","year":"2017","journal-title":"Semin. Cel Dev. Biol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.ydbio.2021.07.002","article-title":"miRNAs as Cell Fate Determinants of Lateral and Paraxial Mesoderm Differentiation from Embryonic Stem Cells","volume":"478","author":"Tuysuz","year":"2021","journal-title":"Dev. Biol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.stem.2019.08.001","article-title":"Design Approaches for Generating Organ Constructs","volume":"25","author":"Xia","year":"2019","journal-title":"Cell Stem Cell"},{"key":"B72","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.biomaterials.2018.08.040","article-title":"Magnetic Field and Nano-Scaffolds with Stem Cells to Enhance Bone Regeneration","volume":"183","author":"Xia","year":"2018","journal-title":"Biomaterials"},{"key":"B73","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1038\/s41551-021-00778-x","article-title":"Induction and Expansion of Human PRRX1+ Limb-bud-like Mesenchymal Cells from Pluripotent Stem Cells","volume":"5","author":"Yamada","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"B74","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1093\/toxsci\/kfaa180","article-title":"Effects of an Environmentally Relevant Mixture of Organophosphate Esters Derived from House Dust on Endochondral Ossification in Murine Limb Bud Cultures","volume":"180","author":"Yan","year":"2021","journal-title":"Toxicol. Sci."},{"key":"B75","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1093\/toxsci\/kfy301","article-title":"Effects of Organophosphate Ester Flame Retardants on Endochondral Ossification in Ex Vivo Murine Limb Bud Cultures","volume":"168","author":"Yan","year":"2019","journal-title":"Toxicol. Sci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1126\/science.1151526","article-title":"Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells","volume":"318","author":"Yu","year":"2007","journal-title":"Science"},{"key":"B77","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.stem.2021.11.009","article-title":"Deciphering the Spatial-Temporal Transcriptional Landscape of Human Hypothalamus Development","volume":"29","author":"Zhou","year":"2022","journal-title":"Cell Stem Cell"},{"key":"B78","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/0012-1606(64)90012-0","article-title":"Development of Fragmented and of Dissociated Limb Bud Mesoderm","volume":"9","author":"Zwilling","year":"1964","journal-title":"Dev. Biol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.863140\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T05:50:50Z","timestamp":1650952250000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2022.863140\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,26]]},"references-count":83,"alternative-id":["10.3389\/fcell.2022.863140"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2022.863140","relation":{},"ISSN":["2296-634X"],"issn-type":[{"type":"electronic","value":"2296-634X"}],"subject":[],"published":{"date-parts":[[2022,4,26]]},"article-number":"863140"}}