Synthetic probes for in vitro purification and in vivo tracking of hepatocytes derived from human pluripotent stem cells

Ji Young Park, Jiyou Han, Hyo Sung Jung, Gyunggyu Lee, Hyo Jin Kim, Gun Sik Cho, Han Jin Park, Choongseong Han, Jong Seung Kim, Jong Hoon Kim

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Hepatocytes derived from human pluripotent stem cells (hPSCs) are promising candidates for cell therapy and drug discovery. However, it remains challenging to efficiently purify hepatocytes from undesired cell types after differentiation and to accurately monitor grafted cells after transplantation. Indocyanine Green (ICG), an FDA-approved, near-infrared (NIR) dye, has been used for various clinical purposes and is exclusively taken up by hepatocytes. However, ICG has a long emission wavelength (λem > 800 nm) that is beyond the detection range of fluorescence-activated cell sorting (FACS) systems. Moreover, it is easily eliminated from hepatocytes, hindering its application for NIR imaging. Here, we designed and synthesized two different probes based on the properties of ICG; 1) hepatocyte purifying agent (HPA, λem = 562 nm) for in vitro sorting and 2) hepatocyte imaging agent (HIA, λem = 817 nm) for efficient in vivo NIR imaging. We obtained highly enriched populations of hPSC-derived hepatocytes (hPSC-Heps) from various hPSC lines using HPA probe-based FACS purification. In addition, HIA labelling and NIR imaging allowed the direct visualization and tracking of grafted hPSC-Heps in animals with liver injuries. These results demonstrated that these two probes could be used as powerful tools with hPSC-Heps in both cell replacement therapy and drug screening.

Original languageEnglish
Article number119431
JournalBiomaterials
Volume222
DOIs
Publication statusPublished - 2019 Nov

Keywords

  • Cell purification
  • Indocyanine green
  • NIR imaging
  • Pluripotent stem cell

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

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