40 Chapter 2 Table 2: Molecular targets for expansion of human pluripotent stem cell-derived cardiomyocytes Pathways Compound Cell type + Age (day) culture format Proliferation markers Expansion (-fold) ref Hippo 67 miRNAs hiPSC-CMs 38 2D, plastic 1.1% pHH3+ N/A DiezCuñado, 2018 Cyclins CDK1, CCNB, CDK4, CCND hiPSC-CMs 60 2D, plastic 25% EdU+, 20% pHH3+ N/A Mohamed, 2018 TGFβ/ SMAD Tgf-β, Wee1, CDK4, CCND hiPSC-CMs 60 2D, plastic 12% EdU+, 15% pHH3+ N/A Mohamed, 2018 PI3K IGF-1 hESC-CMs 1350 2D, plastic 0.4% BrdU+ N/A McDevitt, 2005 Wnt/FGF CHIR99021 FGF1 hiPSC-CMs 30 2D, plastic 30% Ki67+, 20% BrdU+, 4% pHH3+, 4% Auora B+ N/A Fan, 2020 Cell cycle inhibitors (si)RNA: Rb1, Meis2 hiPSC-CMs 35 2D, plastic 30.8 EdU+, 25,8% Ki67+, 5,3% Auora B+ N/A Alam, 2019 Hippo, Wnt, ERK CHIR99021 S1P/LPA hiPSC-CMs 0-2 2D, plastic 40% Ki67+, 4% pHH3+ 1.5 Sharma, 2018 Mevalonate Compound 3 hiPSC-derived cardiac organoids 18 3D, ultra-low attachment plates 7.5% Ki67+, 1% pHH3+ 1.5 Mills, 2019 Wnt CHIR99021 hiPSC-CMs 18 2D, high density microbioreactor 25% Ki67+ 1.5± 0.4 Titmarsh, 2016 Wnt/MAPK BIO+SU+p38i hiPSC-CMs 18 2D, plastic 3% EdU+, 1.5% BrdU+ 1.5± 0.5 Uosaki, 2013 Mevalonate Compound 65 hiPSC-derived cardiac organoids 1416 3D 5% Ki67+, 0.6% pHH3+ 2 Mills, 2017 Wnt Wnt3a conditioned medium hESC-derived Isl1 cardiovascular progenitors 6 2D, plastic 6,8% pHH3+ 6 Qyang, 2007 Activin/nodal, FGF/Wnt A83-01, bFGF, CHIR hiPSC-CMCs 1215 2D, plastic 72.7 ± 1.5% Ki67+ 11 Vahdat, 2022 Wnt CHIR99021 hiPSC-CM 12 3D, stirred spinner cultures 50% G2/M -phase+ 14-16 Laco, 2020 IL6/bFGF IL6RIL6 chimera, bFGF hiPSC-CM 14 2D, suspension culture system N/A, Multiple passaging 25 Amit, 2011 FOXO inhibition AS1842856 hiPSC-CM 10 2D, plastic N/A, Multiple passaging ~40 Schade, 2022 Hedgehog DOX, SB, IGF1, SAG hiPSC-CPCs 5 2D, plastic 8% GLI1 mRNA, 6% PTCH1 mRNA 75 Birket, 2015 Wnt/Insulin /Akt CHIR99021, Cell-cell contact inhibition hiPSC-CMs 11 2D, plastic 6% pHH3+, 20% Ki67+, 35% CCND+, Multiple passaging 250 Buikema, 2020; Maas, 2021
RkJQdWJsaXNoZXIy MTk4NDMw