Mesenchymal stem cell-derived exosomes (MSC-Exo) have attracted much attention for their "cell-free" therapies.

It provides a promising strategy for skeletal tissue regeneration. However, the regeneration capacities of exosomes are susceptible to MSC sources, as well as cell status, and further improvements are usually required.

Recently, a research team led by Dr. ZHAO Xiaoli from the Shenzhen Institute of Advanced Technology (SIAT) of the Chinese Academy of Sciences (CAS), along with collaborators from the University of Hong Kong-Shenzhen Hospital, has developed a strategy of genetically engineered stem cells by bone morphogenetic protein-2 (BMP2) gene to produce exosomes (MSC-BMP2-Exo) with enhanced bone regeneration potency.

The study was published in the Journal of Nanobiotechnology on March 15.

Exosomes are nano-sized vesicles secreted by living cells containing proteins, RNAs and metabolites. As a natural means for cellular communication, exosomes can transport their contents to recipient cells to regulate their functions and behaviors. Stem cell derived exosomes have been found an important mediator for regulation of tissue regeneration.

In this study, the researchers adapted a stem cell-mediated gene therapy (MSC-GT) strategy and applied it in bone regeneration. BMP2-modified MSCs function as cellular factories. These factories effectively produce exosomes with designed and enhanced therapeutic effects.

In vitro and in vivo studies through activating BMP2/Smad signaling pathway proved that the enhanced bone regeneration function was attributed to the synergistic effect of the content derived from MSCs and the up-regulated BMP2 gene expression.

"The safety of drug delivery vehicles is important, and exosomes produced by these MSCs exhibited excellent biocompatibility," said Dr. ZHAO, "in addition, plasmid DNAs only induce temporary gene expression modulation, which avoids the risks of insertional mutation."

By DNA tracking, a proportion of plasmid DNAs were re-encapsulated by mediator MSCs and delivered to the recipient cells through exosomes.

Exosomes derived from BMP2-engineered MSCs promote bone regeneration. (Image by SIAT) 

Written by ZHANG Xiaomin (Shenzhen Institute of Advanced Technology)

Source: Chinese Academy of Sciences