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Commitment of human mesenchymal stromal cells to skeletal lineages is independent of their morphogenetic capacity

World Journal of Stem cells 2023年第7期15卷 701-712页

作者： Jessica Cristina Marín-Llera Damián García-García Estefania Garay-Pacheco Victor Adrian Cortes-Morales Juan Jose Montesinos-Montesinos Jesus Chimal-Monroy Medicina Genómica y Toxicología Ambiental Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoCoyoacan 04510Mexico Laboratorio de Células Troncales Mesenquimales Unidad de Investigación Médica en Enfermedades OncológicasHospital de Oncología Centro Medico Nacional Siglo XXIInstituto Mexicano del Seguro SocialMexico City 06720Mexico Departamento de Medicina Genómica y Toxicología Ambiental Instituto de Investigaciones BiomédicasUniversidad Nacional Autónoma de MéxicoCoyoacan 04510Mexico

BACKGROUND mesenchymal stromal cells(MSCs)are multipotent cell populations obtained from fetal and adult tissues.They share some characteristics with limb bud mesodermal cells such as differentiation potential into osteogenic,chondrogenic,and tenogenic lineages and an embryonic mesodermal origin.Although MSCs differentiate into skeletal-related lineages in vitro,they have not been shown to selforganize into complex skeletal structures or connective tissues,as in the limb.In this work,we demonstrate that the expression of molecular markers to commit MSCs to skeletal lineages is not sufficient to generate skeletal elements in vivo.AIM To evaluate the potential of MSCs to differentiate into skeletal lineages and generate complex skeletal structures using the recombinant limb(RL)system.METHODS We used the experimental system of RLs from dissociated-reaggregated human placenta(PL)and umbilical cord blood(UCB)MSCs.After being harvested and reaggregated in a pellet,cultured cells were introduced into an ectodermal cover obtained from an early chicken limb bud.Next,this filled ectoderm was grafted into the back of a donor chick embryo.Under these conditions,the cells received and responded to the ectoderm’s embryonic signals in a spatiotemporal manner to differentiate and pattern into skeletal elements.Their response to differentiation and morphogenetic signals was evaluated by quantitative poly-merase chain reaction,histology,immunofluorescence,scanning electron microscopy,and in situ hybridization.RESULTS We found that human PL-MSCs and UCB-MSCs constituting the RLs expressed chondrogenic,osteogenic,and tenogenic molecular markers while differentially committing into limb lineages but could not generate complex structures in vivo.MSCs-RL from PL or UCB were committed early to chondrogenic lineage.Nevertheless,the UCB-RL osteogenic commitment was favored,although preferentially to a tenogenic cell fate.These findings suggest that the commitment of MSCs to differentiate into skeletal lineages differs according to the sou

关键词： Human mesenchymal stromal cells Recombinant limbs mesenchymal stromal cell morphogene-sis mesenchymal stromal cell in vivo differentiation Skeletal tissues

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