# Schwann cells modified to secrete MANF is a potential cellular therapy for peripheral nerve regeneration

## TL;DR

This study shows that Schwann cells can be modified to continuously deliver MANF, a protein that promotes nerve regeneration, offering a new therapy for nerve injuries.

## Contribution

Programming Schwann cells to locally and continuously deliver MANF for peripheral nerve regeneration is a novel therapeutic approach.

## Key findings

- Exogenous MANF promotes growth of all adult sensory neuron subtypes and Schwann cell proliferation and migration.
- Local and repeated MANF administration improves axon regeneration in mouse nerve injury models.
- Engineering Schwann cells to secrete MANF enhances nerve repair outcomes.

## Abstract

Effective therapies for peripheral nerve repair are still lacking despite active research in this field over the past years. The limited knowledge of biomolecules that equally promote axon regeneration and glial cell dynamics, which are critical for nerve regeneration, poses a major challenge in developing effective therapies. Here, we showed that the neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) equally promotes axon regeneration and glial cell dynamics favorable for nerve regeneration. Using adult rodent models, we showed that the endogenous expression of MANF is restricted to non-peptidergic sensory neurons. However, supplementation of exogenous MANF promoted the growth of all subtypes of adult sensory neurons. We also demonstrated that exogenous MANF promotes the proliferation and migration of adult primary Schwann Cells (SCs). Furthermore, we showed that local and repeated administration of MANF to injured nerves promotes axon regeneration in mice models. Finally, we devised a therapeutic approach by programming nerve-resident SCs to locally and continuously deliver MANF to injured nerves and showed that this approach improves axon regeneration. Overall, this work developed a therapeutic approach by harnessing the power of SCs as a local delivery system for MANF for nerve repair.

The online version contains supplementary material available at 10.1186/s13619-025-00247-9.