LNGFR+THY-1+ human pluripotent stem cell-derived neural crest-like cells have the potential to develop into mesenchymal stem cells

Takehito Ouchi, Satoru Morikawa, Shinsuke Shibata, Kimiko Fukuda, Hironobu Okuno, Takumi Fujimura, Tatsuo Kuroda, Manabu Ohyama, Wado Akamatsu, Taneaki Nakagawa, Hideyuki Okano

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
JournalDifferentiation
DOIs
Publication statusAccepted/In press - 2015 Oct 14

Fingerprint

Pluripotent Stem Cells
Neural Crest
Mesenchymal Stromal Cells
Induced Pluripotent Stem Cells
Multipotent Stem Cells
Chick Embryo
Embryonic Stem Cells
Plastics
Cartilage
Fluorescence
Fats
Medicine
Bone and Bones
Survival
Serum
Population

Keywords

  • LNGFR
  • Mesenchymal stem cells
  • Neural crest cells
  • THY-1

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology
  • Molecular Biology
  • Cancer Research

Cite this

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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.",
keywords = "LNGFR, Mesenchymal stem cells, Neural crest cells, THY-1",
author = "Takehito Ouchi and Satoru Morikawa and Shinsuke Shibata and Kimiko Fukuda and Hironobu Okuno and Takumi Fujimura and Tatsuo Kuroda and Manabu Ohyama and Wado Akamatsu and Taneaki Nakagawa and Hideyuki Okano",
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T1 - LNGFR+THY-1+ human pluripotent stem cell-derived neural crest-like cells have the potential to develop into mesenchymal stem cells

AU - Ouchi, Takehito

AU - Morikawa, Satoru

AU - Shibata, Shinsuke

AU - Fukuda, Kimiko

AU - Okuno, Hironobu

AU - Fujimura, Takumi

AU - Kuroda, Tatsuo

AU - Ohyama, Manabu

AU - Akamatsu, Wado

AU - Nakagawa, Taneaki

AU - Okano, Hideyuki

PY - 2015/10/14

Y1 - 2015/10/14

N2 - 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.

AB - 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.

KW - LNGFR

KW - Mesenchymal stem cells

KW - Neural crest cells

KW - THY-1

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