Details

Autor(en) / Beteiligte

• Foo, Kylie S.
• Lehtinen, Miia L.
• Leung, Chuen Yan
• Lian, Xiaojun
• Xu, Jiejia
• Keung, Wendy
• Geng, Lin
• Kolstad, Terje R.S.
• Thams, Sebastian
• Wong, Andy On-tik
• Wong, Nicodemus
• Bylund, Kristine
• Zhou, Chikai
• He, Xiaobing
• Jin, Shao-Bo
• Clarke, Jonathan
• Lendahl, Urban
• Li, Ronald A.
• Louch, William E.
• Chien, Kenneth R.

Titel

Human ISL1+ Ventricular Progenitors Self-Assemble into an In Vivo Functional Heart Patch and Preserve Cardiac Function Post Infarction

Ist Teil von

• Molecular therapy, 2018-07, Vol.26 (7), p.1644-1659

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 × 3 mm × 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. The authors identified a human ventricular progenitor (HVP) population that can expand, differentiate, self-assemble, and mature into a 3D functional ventricular patch in vivo. They demonstrate that transplantation of HVPs under the kidney capsule generated a 7 mm × 3 mm × 4 mm myocardial patch while transplantation following myocardial infarction can largely preserve myocardial contractile function.