Stem cell differentiation with consistent lineage commitment induced by a flash of ultrafast-laser activation in vitro and in vivo

Recent technological advancements on stem cell differentiation induction have been making great progress in stem cell research, regenerative medicine, and therapeutic applications. However, the risk of off-target differentiation limits the wide application of stem cell therapy strategies. Here, we report a non-invasive all-optical strategy to induce stem cell differentiation in vitro and in vivo that activates individual target stem cells in situ by delivering a transient 100-ms irradiation of a tightly focused femtosecond laser to a submicron cytoplasmic region of primary adipose-derived stem cells (ADSCs). The ADSCs differentiate to osteoblasts with stable lineage commitment that cannot further transdifferentiate because of simultaneous initiation of multiple signaling pathways through specific Ca2+ kinetic patterns. This method can work in vivo to direct mouse cerebellar granule neuron progenitors to granule neurons in intact mouse cerebellums through the skull. Hence, this optical method without any genetic manipulations or exogenous biomaterials holds promising potential in biomedical research and cell-based therapies. [Display omitted] •A transient 100-ms non-invasive photoactivation induces stem cell differentiation•Differentiated ADSCs are stable and cannot transdifferentiate further•This non-invasive method works in vivo in intact cerebellums through skull•Simultaneous activation of multiple signaling pathways work for lineage commitment Tang et al. report an all-optical technology to induce stem cell differentiation by introducing a transient 100-ms photoactivation of a tightly focused femtosecond laser to individual stem cells. This non-invasive method can induce stable differentiation of adipose-derived stem cells in vitro and granule neuron progenitors in intact cerebellums of mice in vivo.