Bone marrow-derived cells can acquire cardiac stem cells properties in damaged heart.
Bottom Line: However, there is no direct evidence, so far, that BM cells can generate cardiac stem cells (CSCs).Following haematological reconstitution and MI, CSCs were cultured from cardiac explants to generate 'cardiospheres', a microtissue normally originating in vitro from CSCs.These were all green fluorescent (i.e. BM derived) and contained cells capable of initiating differentiation into cells expressing the cardiac marker Nkx2.5.
Affiliation: Institut Pasteur-Cenci Bolognetti Foundation, Department of Experimental Medicine, University of Rome La Sapienza, Rome, Italy.Show MeSH
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Mentions: CSs grow by expansion of a central core of immature cells, which initiate differentiation in the course of their displacement to the periphery of the sphere; this results in the appearance of a small number of cells positive for Nkx2.5, a transcription factor representing an early cardiac marker, and occasionally Troponin I, a latter cytoplasmic marker . A very low level of in vitro differentiation of a type of Kit+ CSC was also reported by Anversa’s group . A representative pool of about 120 CSs, derived from six different transplanted mice, were collected and individually stained with antibodies against Nkx2.5 or Troponin I to evaluate both antibody staining and GFP fluorescence. Confocal analysis shows cells that express GFP together with Nkx2.5 (Figs 3A, B and S2). The percentage of GFP+ cells co-expressing Nkx2.5 is rather variable, ranging between 5% and 50% and depends on the developmental stage of the CSs. Conversely, a very low level of GFP, if any, is stained by anti-TnI-antibody (data not shown). This suggests that cells, which occasionally commit to cardiomyocyte differentiation (i.e. are Nkx2.5+), progressively extinguish Kit/GFP expression, while up-regulating cardiac-specific genes. Interestingly, when a GFP+ CS is dissociated and the resulting cells are replated in fibronectin, the kit/GFP gene is substantially down-regulated; however, if the cells are again grown on polylisine, GFP expression is reactivated (Fig. 3C). This is in agreement with previous findings by Messina et al. . Thus, BM-derived cells present in the CS may express cardiac markers.
Affiliation: Institut Pasteur-Cenci Bolognetti Foundation, Department of Experimental Medicine, University of Rome La Sapienza, Rome, Italy.