title: Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold.
abstract: Functional engineering of musculoskeletal tissues generally involves the use of differentiated or progenitor cells seeded with specific growth factors in biomaterial scaffolds. Ideally, the scaffold should be a functional and structural biomimetic of the native extracellular matrix and support multiple tissue morphogenesis. We have previously shown that electrospun, three-dimensional nanofibrous scaffolds that morphologically resemble collagen fibrils are capable of promoting favorable biological responses from seeded cells, indicative of their potential application for tissue engineering. In this study, we tested a three-dimensional nanofibrous scaffold fabricated from poly(epsilon-caprolactone) (PCL) for its ability to support and maintain multilineage differentiation of bone marrow-derived human mesenchymal stem cells (hMSCs) in vitro. hMSCs were seeded onto pre-fabricated nanofibrous scaffolds, and were induced to differentiate along adipogenic, chondrogenic, or osteogenic lineages by culturing in specific differentiation media. Histological and scanning electron microscopy observations, gene expression analysis, and immunohistochemical detection of lineage-specific marker molecules confirmed the formation of three-dimensional constructs containing cells differentiated into the specified cell types. These results suggest that the PCL-based nanofibrous scaffold is a promising candidate scaffold for cell-based, multiphasic tissue engineering.
authors.affiliation: Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Building 50, Room 1503, MSC 8022, Bethesda, MD 20892-8022, USA.
authors.forename: Wan-Ju
authors.initials: WJ
authors.lastname: Li
authors.forename: Richard
authors.initials: R
authors.lastname: Tuli
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Huang
authors.forename: Patrice
authors.initials: P
authors.lastname: Laquerriere
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D053674:Aggrecans; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000235:genetics; D024022:Fibrillar Collagens / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D006651:Histocytochemistry; D006801:Humans; D058574:Integrin-Binding Sialoprotein; D037181:Lectins, C-Type; D008071:Lipoprotein Lipase / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures / Q000737:chemistry*; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D015675:Osteocalcin / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics; D011091:Polyesters / Q000737:chemistry*; D011509:Proteoglycans / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics
chemical_list: D053674:Aggrecans; D016326:Extracellular Matrix Proteins; D024022:Fibrillar Collagens; C546871:IBSP protein, human; D058574:Integrin-Binding Sialoprotein; D037181:Lectins, C-Type; D047495:PPAR gamma; D011091:Polyesters; D011509:Proteoglycans; D012795:Sialoglycoproteins; D015675:Osteocalcin; C016240:polycaprolactone; D008071:Lipoprotein Lipase; D000469:Alkaline Phosphatase