Molecular understanding of hierarchy and lineage of mesenchymal stem cells in vivo

Kenji Kawabe, Takeshi Takarada

Research output: Contribution to journalArticle

Abstract

Mesenchymal stem cell (MSC) is a type of tissue stem cell. In clinical studies, cultured MSCs have shown important therapeutic effects on diseases via the reduction of neurological defects and regulation of immune responses. However, in vivo MSC localization, function, and properties are poorly understood; therefore, the molecular understanding of MSCs hierarchy is less advanced compared to hematopoietic stem cell hierarchy. To address these issues, we developed a method that enables us to visualize MSCs, manipulate their function, and analyze their molecular biology in vivo. Paired-related homeobox 1 (Prrx1)-positive cells are transiently observed during limb skeletal development in mice. Prrx1-positive cells form heterogeneous populations comprising multiple mesenchymal progenitors with different lineages that are developing into osteoblasts, chondrocytes, adipocytes, fibroblasts, and tendon and ligament cells. Our results suggest that osteoblast differentiation in the calvaria begins at the Prrx1+Sca1+ MSC stage with sequential progression to Prrx1+Sca1- cells, then Osterix+Prrx1-Sca1- osteoblast precursors, which eventually form mature α1(I)-collagen+ osteoblasts. Using Runt-related transcription factor 2 (Runx2) conditional knockout mice, furthermore, we found that the essential period of Runx2 function in intramembranous ossification likely begins at the Prrx1+Sca1+ MSC stage and ends at the Osterix+Prrx1-Sca1- osteoblast precursor stage (before mature the α1(I)-collagen+ osteoblasts appear). This approach will enable us to understand the in vivo molecular biology features of MSCs, leading to their therapeutic applications for tissue repair and regeneration. This development can also contribute to the field of pluripotent stem cell by enabling the transplantation of lineage-restricted mesenchymal progenitors.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalNihon yakurigaku zasshi. Folia pharmacologica Japonica
Volume153
Issue number2
DOIs
Publication statusPublished - Jan 1 2019

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Homeobox Genes
Mesenchymal Stromal Cells
Osteoblasts
Molecular Biology
Collagen
Pluripotent Stem Cells
Stem Cell Transplantation
Therapeutic Uses
Chondrocytes
Hematopoietic Stem Cells
Ligaments
Adipocytes
Osteogenesis
Skull
Knockout Mice
Tendons
Regeneration
Transcription Factors
Stem Cells
Extremities

ASJC Scopus subject areas

  • Pharmacology

Cite this

Molecular understanding of hierarchy and lineage of mesenchymal stem cells in vivo. / Kawabe, Kenji; Takarada, Takeshi.

In: Nihon yakurigaku zasshi. Folia pharmacologica Japonica, Vol. 153, No. 2, 01.01.2019, p. 67-72.

Research output: Contribution to journalArticle

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