mRNA-Engineered Stem Cells Produce Nerve Growth Factor and Induce Neurite Outgrowth in Recipient Cells.

Innervation is essential for tissue healing, yet strategies to enhance nerve growth during repair remain limited. Here, we show that chemically modified messenger RNA (cmRNA) encoding nerve growth factor (NGF) can stimulate neurogenic responses in vitro. NGF cmRNA was delivered to human bone marrow-derived mesenchymal stem cells using lipid carriers, leading to efficient NGF production. In co-culture, NGF-secreting stem cells induced differentiation of neural crest-derived PC-12 cells, as evidenced by increased neurite outgrowth and branching. Proteomic analyses revealed activation of neurogenesis-related pathways in both cell types. Notably, NGF cmRNA-transfected stem cells produced lower NGF levels than recombinant protein yet achieved comparable neurite-outgrowth response, demonstrating the efficiency of the transcript-based approach. These findings demonstrate that NGF cmRNA can induce NGF production by hMSCs and promote neurite outgrowth in NGF-responsive PC12 cells in vitro. This approach may provide the neurotrophic component of future regenerative strategies combining NGF cmRNA with osteogenic signals; however, its effects on functional tissue innervation and bone healing remain to be established in vivo.