Polycystin-1 Enhances Stemmness Potential of Umbilical Cord Blood-Derived Mesenchymal Stem Cells

Int J Mol Sci. 2021 May 4;22(9):4868. doi: 10.3390/ijms22094868.

Abstract

Polycystic Kidney Disease (PKD) is a disorder that affects the kidneys and other organs, and its major forms are encoded by polycystin-1 (PC1) and polycystin-2 (PC2), as PKD1 and PKD2. It is located sandwiched inside and outside cell membranes and interacts with other cells. This protein is most active in kidney cells before birth, and PC1 and PC2 work together to help regulate cell proliferation, cell migration, and interactions with other cells. The molecular relationship and the function between PKD1 and cancer is well known, such as increased or decreased cell proliferation and promoting or suppressing cell migration depending on the cancer cell type specifically. However, its function in stem cells has not been revealed. Therefore, in this study, we investigated the biological function of PC1 and umbilical cord blood-derived mesenchymal stem cell (UCB-MSC). Furthermore, we assessed how it affects cell migration, proliferation, and the viability of cells when expressed in the PKD1 gene. In addition, we confirmed in an ex vivo artificial tooth model generated by the three-dimension printing technique that the ability to differentiate into osteocytes improved according to the expression level of the stemness markers when PKD1 was expressed. This study is the first report to examine the biological function of PKD1 in UCB-MSC. This gene may be capable of enhancing differentiation ability and maintaining long-term stemness for the therapeutic use of stem cells.

Keywords: PKD1; osteogenic differentiation; stemness; umbilical cord blood-derived mesenchymal stem cell (UCB-MSC).

MeSH terms

  • A549 Cells
  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Cell Differentiation / genetics*
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Cell- and Tissue-Based Therapy / methods
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Fetal Blood / cytology
  • Fetal Blood / metabolism
  • Gene Expression
  • HEK293 Cells
  • Humans
  • MCF-7 Cells
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Osteocytes / cytology
  • Osteocytes / metabolism*
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • TRPP Cation Channels / genetics*
  • TRPP Cation Channels / metabolism
  • Transfection
  • Transgenes

Substances

  • Core Binding Factor Alpha 1 Subunit
  • NANOG protein, human
  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RUNX2 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • TRPP Cation Channels
  • polycystic kidney disease 1 protein
  • Alkaline Phosphatase