Spatio-temporal metabolokinetics and therapeutic effect of CD106+ mesenchymal stem/stromal cells upon mice with acute lung injury

Cell Biol Int. 2023 Apr;47(4):720-730. doi: 10.1002/cbin.11976. Epub 2022 Dec 9.

Abstract

Longitudinal investigations have revealed the unique attributes of mesenchymal stem/stromal cells (MSCs) in regenerative medicine. However, the spatio-temporal metabolokinetics and efficacy of MSCs with vascular cell adhesion molecule 1 (also known as CD106) expression in phenotypes and therapeutic effect upon acute lung injury (ALI) mice are largely obscure. For the purpose, we took advantage of the "3IL"-based strategy and Lentivirus-mediated green fluorescent protein (GFP) delivery for the generation of the CD106+ subset (denote as CD106+ -MSCs) from umbilical cord-derived MSCs (denote as NT-MSCs). Therewith, the cellular phenotypes of CD106+ -MSCs including immunophenotypes, multilineage differentiation potential towards adipocytes and osteoblasts were confirmed by flow cytometry and qRT-PCR assay. Meanwhile, multifaceted characteristics of transcriptomic features were analyzed by utilizing the RNA-SEQ and bioinformatics. Furthermore, to compare the therapeutic effects and spatio-temporal dynamics of CD106+ -MSCs, we conducted in vivo fluorescent tracer, hematoxylin and eosin staining, blood smear, blood routine and cytokine detection in mice. Herein, we generated CD106+ -MSCs with GFP expression and confirmed the conservative property of phenotypes. Compared to NT-MSCs with minimal CD106 expression, CD106+ -MSCs manifested consistent distribution and metabolokinetics in vivo but with preferable ameliorative effect upon the pathological appearance and proinflammatory cytokine secretion in ALI mice. Collectively, our data indicated the preferable therapeutic effects of CD106+ -MSCs upon ALI mice, which would benefit the further exploration of the CD106+ subset for pulmonary diseases and investigational new drug application purposes.

Keywords: ALI; CD106+-MSCs; cellular phenotypes; in vivo fluorescent tracer; transcriptome analyses.

MeSH terms

  • Acute Lung Injury* / metabolism
  • Animals
  • Cell Differentiation
  • Cytokines / metabolism
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells* / metabolism
  • Mice
  • Vascular Cell Adhesion Molecule-1 / genetics
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Vascular Cell Adhesion Molecule-1
  • Cytokines