Stem cells can produce a variety of specific tissues and are increasingly being used medically to replace bones or cartilage. But stem cells are also present in cancer tissues, where they are involved in the progression of tumors and in metastasis. In turn, nerves are essential for regulating the physiological and regenerative processes in which stem cells participate. Little is known about the interactions between stem cells and neurons in regenerating tissues and in cancer.

Comparison of stem cell types in tissue regeneration

A research team led by Thimios Mitsiadis, professor at the Institute for Oral Biology at the University of Zurich, has now published two studies on the subject. They show how stem cells promote neuronal growth in tissue regeneration and cancer progression. In the first work, the scientists compared the interaction of neurons with two different human stem cell types: dental pulp and bone marrow stem cells. Both can mature into different cell types such as bone, cartilage and fat cells. Bone marrow stem cells are isolated from skeletal bones and are the gold standard for bone regeneration. A promising alternative are dental pulp stem cells, which are obtained from the inside of the tooth.

Dental stem cells are heavily nerved

For their work, the researchers used “organ-on-a-chip” technology – small 3D biochips that simulate the basic functions of human organs and tissues. They were able to show that both types of stem cells promote the growth of nerve cells. However, the dental pulp stem cells produced better results than the bone marrow stem cells: they produced elongated neurons, formed dense neuronal networks and made close contacts with the nerves.

“Dental stem cells produce specific molecules that are central to the growth and attraction of neurons. They are therefore innervated, »says Mitsiadis. Due to the formation of such extensive networks and the establishment of numerous contacts, the scientists suspect that dental stem cells make intact connections to facial nerves. “These cells are therefore a promising option for the regeneration of functional facial tissues that are correctly equipped with nerves,” added co-author and junior group leader Pierfrancesco Pagella.

Cancer stem cells also promote nerve growth

In the second study, the research team investigated the interaction between nerves and cancer stem cells found in ameloblastoma – an aggressive oral cancer. They first showed that ameloblastomas have stem cell properties and are innervated by facial nerves. Isolated ameloblastoma cells retained their stem cell properties even in the “organ-on-a-chip” devices, attracted nerves and made contact with them.

“It seems that nerves are fundamental to the survival and functioning of cancer stem cells,” explains Pagella. “Our results create new opportunities for cancer treatment with drugs that interfere with the communication between nerve cells and cancer stem cells,” added Mitsiadis. The combination of modern molecular and imaging methods as well as “organ-on-a-chip” technology make it possible to investigate the functions of neurons and their interactions with different stem cell types in both healthy and diseased tissue, said Mitsiadis.

The study was published in University of Zurich