title: LNGFR+THY-1+human pluripotent stem cell-derived neural crest-like cells have the potential to develop into mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSCs) are defined as non-hematopoietic, plastic-adherent, self-renewing cells that are capable of tri-lineage differentiation into bone, cartilage or fat in vitro. Thus, MSCs are promising candidates for cell-based medicine. However, classifications of MSCs have been defined retrospectively; moreover, this conventional criterion may be inaccurate due to contamination with other hematopoietic lineage cells. Human MSCs can be enriched by selection for LNGFR and THY-1, and this population may be analogous to murine PDGFRα+Sca-1+cells, which are developmentally derived from neural crest cells (NCCs). Murine NCCs were labeled by fluorescence, which provided definitive proof of neural crest lineage, however, technical considerations prevent the use of a similar approach to determine the origin of human LNGFR+THY-1+MSCs. To further clarify the origin of human MSCs, human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs) were used in this study. Under culture conditions required for the induction of neural crest cells, human ESCs and iPSCs-derived cells highly expressed LNGFR and THY-1. These LNGFR+THY-1+neural crest-like cells, designated as LT-NCLCs, showed a strong potential to differentiate into both mesenchymal and neural crest lineages. LT-NCLCs proliferated to form colonies and actively migrated in response to serum concentration. Furthermore, we transplanted LT-NCLCs into chick embryos, and traced their potential for survival, migration and differentiation in the host environment. These results suggest that LNGFR+THY-1+cells identified following NCLC induction from ESCs/iPSCs shared similar potentials with multipotent MSCs.
authors.affiliation: Department of Dentistry and Oral Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Ouchi
authors.affiliation: Department of Dentistry and Oral Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Morikawa
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Shibata
authors.affiliation: Department of Biological Science, Tokyo Metropolitan University, Hachioji-shi, Tokyo, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Fukuda
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Okuno
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; Department of Pediatric Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Pediatric Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kuroda
authors.affiliation: Department of Dermatology, Kyorin University School of Medicine, Mitaka-shi, Tokyo, Japan; Department of Dermatology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ohyama
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan; Center for Genomic and Regenerative Medicine, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Wado
authors.initials: W
authors.lastname: Akamatsu
authors.affiliation: Department of Dentistry and Oral Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Taneaki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Physiology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan. Electronic address: hidokano@a2.keio.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D002642:Chick Embryo; D000066449:Human Embryonic Stem Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009432:Neural Crest / Q000166:cytology / Q000254:growth & development; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D018800:Thy-1 Antigens / Q000235:genetics*
chemical_list: C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D018800:Thy-1 Antigens
keywords: LNGFR; Mesenchymal stem cells; Neural crest cells; THY-1