Health: ENEA explores new stem cell strategy

Two international studies conducted as part of the European RISEUP project, coordinated by ENEA and published in the journals *Journal of Molecular Sciences* and *Stem Cell Research and Therapy*, offer new prospects for the development of innovative therapies in the field of regenerative medicine. According to this research, the fate of stem cells^[1] can be steered toward proliferation or differentiation into fat, bone and neuronal cells through the application of ultra-short electrical pulses (PEF).

“Stem cells are an extremely powerful tool for tissue regeneration, but the success of cell transplantation depends on several factors, including the cells’ caapcity to colonize the injured tissue, survive and differentiate” explained RISEUP project coordinator Claudia Consales, a researcher at the ENEA RED Biotechnology Laboratory. “For this reason,” she continued “it is essential to adopt targeted strategies to promote these processes.

“In addition to transplantation using scaffolds—support structures that facilitate cell engraftment—it is preferable to employ protocols capable of initially stimulating cell proliferation, thereby improving cell survival, and subsequently promoting differentiation. This is because one of the primary obstacles to cell transplantation is the massive death of the implanted cells during the engraftment phase.”

These two studies demonstrated that the fate of stem cells is guided by calcium oscillations induced by ultrashort electrical pulses (PEFs), lasting 100 microseconds and of moderate intensity, which cause the formation of pores in the cell membrane (electroporation)^[2]. In fact, laboratory tests have shown that an increase in the frequency of calcium oscillations induced by PEFs can promote cell proliferation and the maintenance of their undifferentiated state. Conversely, their reduction or disappearance accompanies differentiation processes.

Electroporation induced by electrical stimulation^[3] at varying intensities, is already widely used in biological and clinical settings. For example, temporary electroporation is very useful for transferring genetic material or drugs into cells (electrochemotherapy); permanent electroporation is indicated in cancer therapies because, since the pores do not close, the tumor cell dies without damaging healthy tissue.

“The success of our tests stems precisely from the integration of a well-established electrical stimulation technique with knowledge of calcium’s key role in cellular processes: the combination of these elements has led to an unprecedented result—an effective and easily applicable approach that makes it possible to control the fate of cells” concluded ENEA researcher Claudia Consales.

[1] Studies were conducted on mesenchymal stem cells derived from adipose tissue (MSCs) and on neural stem cells (iNSCs) obtained from induced pluripotent stem cells (iPSCs).

[2] PEFs act by modulating the presence of the calcium ion (Ca²⁺), a positively charged form of calcium, inside the cell. Normally, calcium (Ca) is a neutral chemical element, but when it loses two electrons it becomes Ca²⁺, an ion with a double positive charge. This ion is essential for many cellular and biological functions.

[3] All living cells possess natural electric fields and therefore present a stable electric potential, which can be modified by the application of an external electric field. Furthermore, the effect of electrical stimulation depends on the intensity and duration of the electric field, as well as the type of cell involved.