How do stem cells promote neuronal growth in tissue regeneration and cancer progression?

Written by Sharon Salt, Senior Editor

Nerves are a fundamental aspect for regulating the physiological and regenerative processes that involve stem cells. However, little is known about how stem cells promote neuronal growth in regenerating tissues and in cancer progression.

A team of scientists, led by Thimios Mitsdiadis (University of Zurich, Switzerland), have recently published two studies that elucidate how stem cells can promote neuronal growth in both of these circumstances.

Neurotrophic effects of dental pulp stem cells and bone marrow stem cells

In their first study, which has been published in The FASEB Journal, the investigators compared the neurotrophic effects of human dental pulp stem cells and human bone marrow stem cells on trigeminal and dorsal root ganglia neurons by using microfluidic organ-on-chip devices.

The team demonstrated that both types of stem cells promoted neuronal growth. However, the dental pulp stem cells expressed significantly higher levels of neurotrophins compared with the bone marrow stem cells. Additionally, the dental pulp stem cells induced more elongated neurons, formed dense neuronal networks and established close contacts with nerves compared with bone marrow stem cells.

“Dental stem cells produce specific molecules that are fundamental for the growth and attraction of neurons. Therefore, stem cells are abundantly innervated,” commented Mitsiadis. “Therefore, these cells could represent an attractive choice for the regeneration of functional, properly innervated facial tissues,” added co-author Pierfrancesco Pagella (University of Zurich).

Nerves are fundamental for the survival of cancer stem cells

In their second study, published in Cells, the team investigated the interaction between nerves and cancer stem cells of human ameloblastomas. First, they demonstrated that ameloblastomas contain stem cell properties and are innervated by facial neurons.

Once they isolated the ameloblastoma cells and inserted them into organ-on-chip devices, they were able to retain their stem cell properties, attracted nerves and established contact with them.

“It appears that nerves are fundamental for the survival of cancer stem cells,” explained Pagella. “These results create new possibilities for cancer treatment using drugs that modify the communication between neurons and cancer stem cells,” added Mitsiadis.

To conclude, Mitsiadis stated that: “The combination of advanced molecular and imaging tools and organ-on-a-chip technology offers an exciting opportunity to reveal the hidden functions of neurons and their interactions with various stem cell types, in both healthy and pathological conditions.”

Sources: Pagella P, Miran S, Neto E, Martin I, Lamghari M, Mitsiadis TA. Human dental pulp stem cells exhibit enhanced properties in comparison to human bone marrow stem cells on neurites outgrowth. FASEB J. doi:10.1096/fj.201902482R (2020); Pagella P, Caton J, Meisel C, Mitsiadis TA. Ameloblastomas exhibit stem cell potential, possess neurotrophic properties and establish connections with trigeminal neurons. Cells 9(3), 644 (2020);

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