title: Biomaterials directed in vivo osteogenic differentiation of mesenchymal cells derived from human embryonic stem cells.
abstract: Spontaneous differentiation of human embryonic stem cells (hESCs) is generally inefficient and leads to a heterogeneous population of differentiated and undifferentiated cells, limiting the potential use of hESCs for cell-based therapy and studies of specific differentiation programs. Here, we demonstrate biomaterial-dependent commitment of a mesenchymal cell population derived from hESCs toward the osteogenic lineage in vivo. In skeletal development, bone formation from condensing mesenchymal cells involves two distinct pathways: endochondral and intramembraneous bone formation. In this study, we demonstrate that the hESC-derived mesenchymal cells differentiate and regenerate in vivo bone tissues through two different pathways depending upon the local cues present in a scaffold microenvironment. Hydroxyapatite (HA) was incorporated into biodegradable poly(lactic-co-glycolic acid)/poly(l-lactic acid) (PLGA/PLLA) scaffolds to enhance bone formation. The HA microenvironment stabilized the β-catenin and upregulated Runx2, resulting in faster bone formation through intramembraneous ossification. hESC-derived mesenchymal cells seeded on the PLGA/PLLA scaffold without HA, however, showed minimal levels Runx2, and differentiated via endochondral ossification, as evidenced by formation of cartilaginous tissue, followed by calcification and increased blood vessel invasion. These results indicate that the ossification mechanisms of the hESC-derived mesenchymal stem cells can be regulated by the scaffold-mediated microenvironments, and bone tissue can be formed.
authors.affiliation: School of Chemical and Biological Engineering, Institute for Chemical Processing, Seoul National University, Seoul, Republic of Korea. nshwang@snu.ac.kr
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Hwang
authors.forename: Shyni
authors.initials: S
authors.lastname: Varghese
authors.forename: H Janice
authors.initials: HJ
authors.lastname: Lee
authors.forename: Zijun
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Elisseeff
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001672:Biocompatible Materials; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid