Physical Stimulation Methods Developed for In Vitro Neuronal Differentiation Studies of PC12 Cells: A Comprehensive Review

Author:

Tominami Kanako1,Kudo Tada-aki1ORCID,Noguchi Takuya2ORCID,Hayashi Yohei34,Luo You-Ran5ORCID,Tanaka Takakuni5,Matsushita Ayumu1,Izumi Satoshi1,Sato Hajime6,Gengyo-Ando Keiko1,Matsuzawa Atsushi2ORCID,Hong Guang5ORCID,Nakai Junichi1

Affiliation:

1. Division of Oral Physiology, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan

2. Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan

3. Cell Resource Center for Biomedical Research, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan

4. Graduate School of Life Sciences, Tohoku University, Sendai 980-8577, Japan

5. Division for Globalization Initiative, Tohoku University Graduate School of Dentistry, Sendai 980-8575, Japan

6. Division of Pharmacology, Meikai University School of Dentistry, Sakado 350-0283, Japan

Abstract

PC12 cells, which are derived from rat adrenal pheochromocytoma cells, are widely used for the study of neuronal differentiation. NGF induces neuronal differentiation in PC12 cells by activating intracellular pathways via the TrkA receptor, which results in elongated neurites and neuron-like characteristics. Moreover, the differentiation requires both the ERK1/2 and p38 MAPK pathways. In addition to NGF, BMPs can also induce neuronal differentiation in PC12 cells. BMPs are part of the TGF-β cytokine superfamily and activate signaling pathways such as p38 MAPK and Smad. However, the brief lifespan of NGF and BMPs may limit their effectiveness in living organisms. Although PC12 cells are used to study the effects of various physical stimuli on neuronal differentiation, the development of new methods and an understanding of the molecular mechanisms are ongoing. In this comprehensive review, we discuss the induction of neuronal differentiation in PC12 cells without relying on NGF, which is already established for electrical, electromagnetic, and thermal stimulation but poses a challenge for mechanical, ultrasound, and light stimulation. Furthermore, the mechanisms underlying neuronal differentiation induced by physical stimuli remain largely unknown. Elucidating these mechanisms holds promise for developing new methods for neural regeneration and advancing neuroregenerative medical technologies using neural stem cells.

Funder

Japan Society for the Promotion of Science

Cooperative Research Project Program of the Joint Usage/Research Center at the Institute of Development, Aging, and Cancer, Tohoku University

Publisher

MDPI AG

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