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

Authors
Park, Ji YoungHan, JiyouJung, Hyo SungLee, GyunggyuKim, Hyo JinCho, Gun-SikPark, Han-JinHan, ChoongseongKim, Jong SeungKim, Jong-Hoon
Issue Date
11월-2019
Publisher
ELSEVIER SCI LTD
Keywords
Pluripotent stem cell; Indocyanine green; Cell purification; MR imaging
Citation
BIOMATERIALS, v.222
Indexed
SCIE
SCOPUS
Journal Title
BIOMATERIALS
Volume
222
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/62079
DOI
10.1016/j.biomaterials.2019.119431
ISSN
0142-9612
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 (lambda(em) > 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, lambda(em) = 562 nm) for in vitro sorting and 2) hepatocyte imaging agent (IRA, lambda(em) = 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.
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