Dissecting the hierarchy and lineage of mesenchymal stem cells using mouse genetics as a step toward drug discovery and regenerative medicine

Research output: Contribution to journalReview articlepeer-review

Abstract

The mesenchymal stem cell (MSC) is a type of tissue stem cell. In clinical studies, cultured MSCs have shown important therapeutic effects on diseases via both the reduction of neurological defects and the regulation of immune responses. However, in vivo MSC localization, function, and properties are poorly understood; therefore, the molecular understanding of MSC hierarchy is less advanced compared to hematopoietic stem cell hierarchy. Runt-related transcription factor 2 (Runx2) is an essential transcriptional regulator of osteoblast differentiation from MSCs. Runx2 deficiency in Paired-related homeobox 1 (Prrx1)-derived cells (Runx2 -/-Prrx1 mice) results in defective intramem-branous ossification. Double-positive cells for Prrx1-GFP, and stem cell antigen-1 (Sca1) (Prrx1Sca1 cells) in the calvaria, express Runx2 at lower levels, and are more homogeneous and primitive compared with Prrx1Sca1 cells. Our results suggest that osteoblast differentiation in vivo may begin at the Prrx1Sca1 MSC stage, with sequential progression to Prrx1Sca1 cells, followed by OsterixPrrx1Sca1 osteoblast precursors, which eventually form mature α1(I)-collagen osteoblasts. This research will enable us to better understand the in vivo molecular biology features of MSCs, leading to their therapeutic applications for tissue repair and regeneration.

Original languageEnglish
Pages (from-to)867-871
Number of pages5
JournalYakugaku Zasshi
Volume139
Issue number6
DOIs
Publication statusPublished - 2019

Keywords

  • Hierarchy
  • Mesenchymal stem cell
  • Paired-related homeobox 1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

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