Long-Term Tracking Mesenchymal Stem Cell Differentiation with Photostable Fluorescent Nanoparticles

ACS Appl Mater Interfaces. 2016 May 18;8(19):11925-33. doi: 10.1021/acsami.5b12371. Epub 2016 May 6.

Abstract

Mesenchymal stem cells (MSCs) have proved to be a promising and abundant cell source for tissue and organ repair in regenerative medicine. However, the cell fate, distribution and migration of these transplanted cells are still unclear due to the limited tracking methods. It is desirable to develop a biocompatible and photostable probe to label the MSCs for long-term tracking without affecting the cell proliferation and potency. Herein we apply a recently developed nanoprobe system, in which di(thiophene-2-yl)-diketopyrrolopyrrole (DPP) is covalently linked in the middle of polycaprolactone (PCL) forming the PCL-DPP-PCL polymer complex. Although the PCL-DPP-PCL nanoparticles uptaken by the MSCs did not affect the cell viability, it was interesting that they exhibited different effects on the multilineage potency of the MSCs in the subsequent differentiation in vitro. Specifically, we found that the PCL-DPP-PCL labeling was unfavorable to the MSC osteogenic differentiation, whereas the labeled MSCs exhibited the same adipogenic and chondrogenic differentiations compared to the unlabeled controls as verified by gene expressions and histological staining. Furthermore, the PCL-DPP-PCL nanoparticles remained strong fluorescence intensity even after 4 weeks of differentiation. This study indicated that PCL-DPP-PCL nanoparticles could be used for long-term cell tracing in MSC differentiation into adipogenic and chondrogenic lineages.

Keywords: differentiation; long-term cell tracking; mesenchymal stem cell; nanoparticles; photostability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / drug effects*
  • Cell Tracking / methods*
  • Fluorescent Dyes* / chemistry
  • Fluorescent Dyes* / pharmacology
  • Gene Expression Regulation / drug effects*
  • Humans
  • Mesenchymal Stem Cells* / cytology
  • Mesenchymal Stem Cells* / metabolism
  • Nanoparticles / chemistry*
  • Pyrazoles* / chemistry
  • Pyrazoles* / pharmacology
  • Pyrimidines* / chemistry
  • Pyrimidines* / pharmacology

Substances

  • Fluorescent Dyes
  • N(4)-benzyl-N(6),N(6)-dimethyl-1-1(tert-butyl)-1H-pyrazolo(3,4-d)pyrimidine-6,4-diamine
  • Pyrazoles
  • Pyrimidines