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. 2023 May 13;10(5):587. doi: 10.3390/bioengineering10050587

Table 1.

Doses of hiPSC-CMs within ECTs reported in current preclinical research for cardiac regenerative therapies.

Research Group Dose(s)/ECT Dimensions Experiments
Eschenhagen and Weinberger [12,63] 450 M
(hiPSC-CMs)		 50 × 70 mm In vivo: healthy swine heart

  • Successful engraftment of hiPSC-CMs
4.5 M, 8.5 M, 12 M, 15 M
(hiPSC-CMs)		 15 × 25 mm In vivo: guinea pig cryoinjury model

  • Cell dose dependence on remuscularization of scar

  • Improvement in LV FAS at high dose (12 M)

  • Importance of hiPSC-CM maturity for engraftment
Zhang [58] 4 M/ECT
8 M/2-ECTs
(hiPSC-CMs)		 40 × 20 mm In vivo: swine I/R model of MI

  • 2 ECTs implanted over infarct

  • Improved EF compared to sham and non-cellular implants

  • Decreased LVEDV and infarct size compared to sham and non-cellular implants
Bursac [61] 0.5 M/1 M
(hiPSC-CMs)		 7 × 7 mm In vitro/in vivo:

  • Increased stress generation, force per CM, velocity of action potential at lower cell density

  • No adverse effect on host electrical function
2 M/10 M
(hiPSC-CMs)		 15 × 15 mm
36 × 36 mm		 In vitro:

  • Scale up for proof of concept
Coulombe [60] 7–10 M
(hiPSC-CMs)		 18 × 14 mm In vivo: rat I/R model of MI

  • Trend illustrating improved viable engrafted area of ECTs loaded with proangiogenic factors

  • Correlated with improved vascularization of ECT as well as infarct area with proangiogenic loading of ECTs

  • Improved FS of ECTs with angiogenic factor loading compared to sham
Keller [66] 2.64–5.28 M
(hiPSC-CMs)		 15 × 15 mm In vivo: rat model of MI

  • Improved EF, CO, and regional LV radial and longitudinal strain at 4 weeks
10.56 M
(hiPSC-CMs)		 30 × 30 mm In vitro:

  • Scale up for proof of concept
Zimmerman [64] 2.5 M/ECT
12.5 M/5-ECT
(Neonatal rat CMs)		 ~5 × 10 mm In vivo: rat PL model of MI

  • Generating multiloop ECTs by stacking 5 single loop ECTs

  • Induced systolic wall thickening

  • Improved FAS compared to controls

MI = myocardial infarction, LV = left ventricle, I/R = ischemia-reperfusion, PL = permanent ligation, FAS = fractional area shortening, FS = fractional shortening, LVEDV = left ventricle end diastolic volume, EF = ejection fraction, CO = cardiac output; M = million.