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Human ISL1+ ventric...
Human ISL1+ ventricular progenitors self-assemble into an in vivo functional heart patch and preserve cardiac function post infarction
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Foo, Kylie S (author)
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Lehtinen, Miia L (author)
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Lian, Xiaojun (author)
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Xu, Jiejia (author)
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Keung, Wendy (author)
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Geng, Lin (author)
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Kolstad, Terje R S (author)
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- Thams, Sebastian (author)
- Karolinska Institutet
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Wong, Andy On-tik (author)
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Wong, Nicodemus (author)
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Bylund, Kristine (author)
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- Zhou, Chikai (author)
- Karolinska Institutet
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He, Xiaobing (author)
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- Jin, Shao-Bo (author)
- Karolinska Institutet
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Clarke, Jonathan (author)
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- Lendahl, Urban (author)
- Karolinska Institutet
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Li, Ronald A (author)
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Louch, William E (author)
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- Chien, Kenneth R (author)
- Karolinska Institutet
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Leung, CY (author)
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- ISSN 1525-0016
- Stockholm : Karolinska Institutet, Dept of Cell and Molecular Biology, 2018
- 2018
- English.
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In: Molecular Therapy. - Stockholm : Karolinska Institutet, Dept of Cell and Molecular Biology. - 1525-0016. ; 26:7, s. 1644-1659
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Abstract
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- The generation of human pluripotent stem cell (hPSC)-derived ventricular progenitors and their assembly into a 3-dimensional in vivo functional ventricular heart patch has remained an elusive goal. Herein, we report the generation of an enriched pool of hPSC-derived ventricular progenitors (HVPs), which can expand, differentiate, self-assemble, and mature into a functional ventricular patch in vivo without the aid of any gel or matrix. We documented a specific temporal window, in which the HVPs will engraft in vivo. On day 6 of differentiation, HVPs were enriched by depleting cells positive for pluripotency marker TRA-1-60 with magnetic-activated cell sorting (MACS), and 3 million sorted cells were sub-capsularly transplanted onto kidneys of NSG mice where, after 2 months, they formed a 7 mm x 3 mm x 4 mm myocardial patch resembling the ventricular wall. The graft acquired several features of maturation: expression of ventricular marker (MLC2v), desmosomes, appearance of T-tubule-like structures, and electrophysiological action potential signature consistent with maturation, all this in a non-cardiac environment. We further demonstrated that HVPs transplanted into un-injured hearts of NSG mice remain viable for up to 8 months. Moreover, transplantation of 2 million HVPs largely preserved myocardial contractile function following myocardial infarction. Taken together, our study reaffirms the promising idea of using progenitor cells for regenerative therapy. Correction in Mol Ther. 2021 Jan 6;29(1):409, DOI: 10.1016/j.ymthe.2020.11.015
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- art (subject category)
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- By the author/editor
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Foo, Kylie S
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Lehtinen, Miia L
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Lian, Xiaojun
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Xu, Jiejia
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Keung, Wendy
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Geng, Lin
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show more...
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Kolstad, Terje R ...
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Thams, Sebastian
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Wong, Andy On-ti ...
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Wong, Nicodemus
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Bylund, Kristine
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Zhou, Chikai
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He, Xiaobing
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Jin, Shao-Bo
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Clarke, Jonathan
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Lendahl, Urban
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Li, Ronald A
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Louch, William E
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Chien, Kenneth R
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Leung, CY
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show less...
- Articles in the publication
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Molecular Therap ...
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Molecular therap ...
- By the university
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Karolinska Institutet