Nerve growth factor (NGF) and NGF receptors in mesenchymal stem/stromal cells: Impact on potential therapies

Abstract

Mesenchymal stem/stromal cells (MSCs) are promising for the treatment of degenerative diseases and traumatic injuries. However, MSC engraftment is not always successful and requires a strong comprehension of the cytokines and their receptors that mediate the biological behaviors of MSCs. The effects of nerve growth factor (NGF) and its two receptors, TrkA and p75NTR, on neural cells are well studied. Increasing evidence shows that NGF, TrkA, and p75NTR are also involved in various aspects of MSC function, including their survival, growth, differentiation, and angiogenesis. The regulatory effect of NGF on MSCs is thought to be achieved mainly through its binding to TrkA. p75NTR, another receptor of NGF, is regarded as a novel surface marker of MSCs. This review provides an overview of advances in understanding the roles of NGF and its receptors in MSCs as well as the effects of MSC-derived NGF on other cell types, which will provide new insight for the optimization of MSC-based therapy.

Keywords: P75NTR; TrkA; cellular therapy; mesenchymal stem/stromal cell; nerve growth factor.

FIGURE 1

Overview of NGF/TrkA signaling pathways in neurons and MSCs. A, NGF binds to the extracellular ligand of TrkA and then actives PI3K‐Akt, Ras‐MAPK and PLCγ‐PKC signaling pathways to promote the survival and differentiation of neurons. B, After binding to TrkA, NGF can activate the PI3K/Akt and MAPK/Erk signaling pathways in MSCs. Sirt is also involved in the activation of Akt and Erk, both of which can stimulate the neural differentiation of MSCs. In addition, the activation of Akt can promote the proliferation, chondrogenic differentiation and osteogenic differentiation of MSCs and prevent their apoptosis. MSCs, mesenchymal stem/stromal cells; NGF, nerve growth factor