Significance: The belief in the potency of stem cells has resulted in the medical applications of numerous cell types for organ repair, often with the low adherence to methodological stringency. Such uncritical enthusiasm is mainly presented in the approaches employing so-called mesenchymal stem cells (MSC), for the treatment of numerous, unrelated conditions. However, it should be stressed that such broad clinical applications of MSC are mostly based on the belief that MSC can efficiently differentiate into multiple cell types, not only osteoblasts, chondrocytes and adipose cells. Recent Advances: Studies employing lineage tracing established more promising markers to characterize MSC identity and localization in vivo and confirmed the differences between MSC isolated from various organs. Furthermore, preclinical and clinical experiments proved that transdifferentiation of MSC is unlikely to contribute to repair of numerous tissues, including the heart. Therefore, the salvage hypotheses, like MSC fusion with cells in target organs or the paracrine mechanisms, were proposed to justify the widespread application of MSC and to explain transient, if any, effects.
Critical issues: The lack of standardization concerning the cells markers, their origin and particularly the absence of stringent functional characterization of MSC, leads to propagation of the worrying hype despite the lack of convincing therapeutic efficiency of MSC.
Future directions: The adherence to rigorous methodological rules is necessary to prevent the application of procedures which can be dangerous for patients and scientific research on the medical application of stem cells. Antioxid. Redox Signal. 00, 000-000.
Keywords: cardiac regeneration; clinical trial; heme oxygenase-1; inflammation; mesenchymal stem cell; transplantation.