Table 2 Clinical applications of SMs sheets and iPS-CMs sheets for the treatment of heart diseases

SMs

An idiopathic DCM patient with an LVAD

First-in-human clinical trial

1

1 year

LVEF and LVDD were improved after 3 months

No life-threatening arrhythmia had occurred

[19]

Wall motion improved first on the anterior and lateral surfaces and then on the other surface in the longer term

BNP levels declined and reached the normal range

The patient was able to discontinue using an LVAD and avoid cardiac transplantation

Cardiomyopathy patients without LVADs

Phase I clinical trial

15 ICM patients

More than 3 years

LVDD and LVEF showed significant improvement during 1 year

No lethal arrhythmias such as sustained VT and ventricular fibrillation were observed

[20]

The NYHA classification had improved in all patients

End-systolic wall stress was significantly decreased at 6 months

Survival rate was 100% at 1 year and 90.9% at 3 years

No cardiac death event occurred within 3 years

Exercise capacity was improved via the 6MWD

A significant reduction of serum BNP level was observed

Reductions in PAP, PCWP, and PVR were observed

Reduction of LV wall stress was noted

12 DCM patients

More than 3 years

LVDD and LVEF were not statistically different after the treatment

2 patients with DCM developed congestive heart failure within 6 months

The survival rate was 90.0% at 1 year and 75.0% at 3 years

5 late cardiac deaths occurred within 3 years

Only limited efficacy was observed

Severe chronic HF due to ischemic heart disease

Phase II clinical study

7

26 weeks

LVEF was found improved or unchanged in 5 of the 7 patients

6 arrhythmia events and 3 SAEs occurred, but were all not drug-related

[15]

The NYHA classification was found to improve in 6 of the 7 patients

A clear improvement in exercise tolerance was observed in most patients

End-stage ICM

Long-term clinical follow-up

23

Long-term

LVEF was found to improve or unchanged in 16 of the 23 patients at 6 months and the average increase was 4.9%

4 cases of cardiac unrelated mortality occurred

[62]

The 1- and 5-year survival rates were 100% and 95% respectively

The 1- and 5-year freedom from composite events were 87% and 62% respectively

The NYHA classification was significantly improved

Substantial improvements in the serum BNP level and the 6MWD were found up to 3 years after the treatment

The hemodynamic variables did not significantly change for up to 3 years after the treatment

Pediatric DCM

Case study

1

6 months

LV volume remained unchanged

No arrhythmia or critical adverse events were observed

[16]

LV contraction was sustainably ameliorated

Ross heart failure classification improved from the third to the first degree at 3 months, and no deterioration was observed

Cardiopulmonary exercise exhibited a trend of improvement via the 6MWD

Cold extremities, respiratory distress, and excessive sweating improved after sheet implantation

iPS-CMs

ICM patients

A doctor-initiated clinical trial

3

6 months

The NYHA classification improved after 6 months: 2 patients from III to II and 1 patient from III to I

Three patients were all progressing well

–

Three patients were all without disease progression during follow-up