Embryonic stem cells (ESCs) have pluripotency and can develop into different tissues. If a source of adult cells with the same ability could be found, ethical problems associated with the work would disappear.
Now, a German team has grown the sought-after pluripotent stem cells from adult mouse testis. The spermatogonial stem cells (SSCs) differentiate into vascular cells and functional cardiomyocytes.
Gert Hasenfuss and Kerstin Troidl
At yesterday’s Basic Science Hot Line session, Gert Hasenfuss (Georg-August-Universitat Gottingen, Germany) described the functional properties of these cardiac cells. Clusters of beating cardiomyocytes expressed connexion 43 at cell-to-cell contacts, which indicates the presence of gap junctions.
The addition of carbenoxolone, a gap junction uncoupler, significantly decreased recovery. Action potentials typical for pacemaker-, ventricle-, atrial- and Purkinje-like cardiomyocytes were recorded. Beta-adrenergic stimulation with isoproterenol resulted, as predicted, in a significant increase in the magnitude of contractions. Finally, confocal microscopy demonstrated a homogenous increase in calcium throughout the cell, followed by a fine regulated release from intracellular stores.
The amplitudes measured in the SSCderived cells were similar to those in ESC-derived cardiomyocytes; and comparable to adult cardiac myocytes.
Hasenfuss concluded that the cardiomyocytes show action potentials typical of various cardiac cells. They have functional gap junctions and functional calcium cycling: “Adult SCs provide a new source of distinct types of cardiomyocytes for basic research and potential therapeutic action.”
The data presented was based on mice cells and there is some way to go before the work provides practical options in the clinic. Hasenfuss: “It is not established for human tissue. We are in the process of doing this. We have shown the biological principle and therefore I am optimistic that it can be established for human tissue.
The question is how long it will take to find the right way.” In future, because the SSCs could be taken from male patients themselves, it also overcomes the problem of immunological rejection. He said: “It could resolve the ethical problem completely because the cells are taken from adults; and the immunological problem, at least for 50% of the population.”
European researchers have identified a gene which may stimulate the growth of natural bypasses. The discovery could lead to new treatment options for patients with obstructive arterial diseases.
Where blood flow is deficient, the human body tries to compensate by growing bridging arteries, but this spontaneous growth is limited. All previous attempts to stimulate it
have been inconclusive, possibly because the specific physical forces which are the initial triggers for this vessel growth, are insufficient.
Kerstin Troidl (Bad Nauheim, Germany) presented work at same Hot Line session. She and colleagues adapted an animal model to increase these forces, and identified a gene, ABRA, which appears to be the interface between the physical force and the induction of collateral growth.
Using a recombinant adenovirus, ABRA was introduced into animal models and increased the growth of natural bypasses by 70%, compared to the natural response. Troidl said: “Arteriogenesis is, in principle, able to restore the function of an occluded artery. We have discovered a new gene that stimulates the growth of natural bypasses.”