Table 1 Three strategies to generate cardiomyocytes from fibroblasts. The properties of the cells, advantages, and disadvantages of the strategies are shown

Cell state

iPS cells

(pluripotent)

Cardiac progenitor cells

(multipotent)

Differentiated cardiomyocytes

(unipotent)

Properties

1. Pluripotent cells

2. Bypass ethical and legal problems (compared to ES cells)

3. Not accompanied by the problem of immunologic refusal

Multipotent CPCs can generate vascular and cardiac cells

Transdifferentiation without an undifferentiated (intermediate) state (i.e., iPS cells, CPCs)

Advantages

Engraftment of ES cell-derived cardiomyocytes is possible in large animal models, accompanied by improved heart function

A short culture period (weeks) required to produce cardiomyocytes, compared with iPSC-mediated cardiomyocytes

1. In vivo reprogramming

2. Takes 4 weeks to generate functional cardiomyocytes

3. Lack of tumor formation

4. Generating only cardiomyocytes

Disadvantages

1. Risk of teratoma formation

2. A long culture period (months) is required to generate cardiomyocytes

3. Immaturity of stem cell-derived cardiomyocytes

1. Uncertain mechanism of OSKM-mediated CPC induction

2. Risk of tumor formation

1. Immaturity of iCMs

2. Low efficiency of full reprogramming into functional cardiomyocytes

3. iCMs are not proliferative