PREreview of Effect of Cellular and ECM Aging on Human iPSC-derived Cardiomyocyte Performance, Maturity and Senescence

This paper focuses on understanding the effect of ageing on cells and the ECM in the context of cardiovascular diseases. The death of the patient is directly correlated to the age of the patient, as over some time the cell undergoes drastic changes in its ability to respond to the cytokines as well as loses its regenerative properties.

The effect of the microenvironment on the cell’s response is beautifully shown in this paper both in normal as well as in myocardial infarction state. Firstly, markers for senescence and loss of function are established in Fig 1, however, the quantification is not provided. I suggest including graphical quantification of the data would strongly establish the ageing of the cardiomyocytes by the protocol used.

Next, the authors show that decellularized ECM shows age-dependent characteristics. I suggest the addition of quantification for collagen abundance and thickness in Fig 2A. In Fig 2B, there is no explanation regarding the difference in ECM content in young, adult and aged conditions. For example, a decrease in collagen 1 content in adult mice as compared to young followed by a further increase in the aged ECM should be elaborated. Similarly, for fibrillin, the addition of an explanation would be useful. The ECM content depiction could be improved by showing a stacked bar graph.

In fig 3, the ideal coating control would be matrigel as it consists of ECM. Fibronectin is the one of components of the ECM. This would ensure that it’s the cardiac microenvironment-dependent changes in the cell when compared to the unrelated microenvironment. In control, ADAMTS1 is expressed in aged cardiomyocytes, however, it seems that in young ECM, for both young and old cardiomyocytes, ADAMTS1 expression is higher.

Upon I/RI the cell viability decreases and the decrease is dependent on the age of ECM. However, the correlation of survival is not followed by the aged cell in different ECM in fig 5b, which is the major part of the study. The comparison of the aged cell on aged ECM is not consistently compared to young and adult

Overall, the paper explores the critical information that the cells derive from the microenvironment and its importance while treating cardiovascular conditions.