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<p>The ability to regulate stem cell differentiation into organized neural tissue remains a major challenge in regenerative medicine, particularly in the development of physiologically relevant three-dimensional (3D) organoid models. Photobiomodulation (PBM) is a new non-invasive technology for controlling cellular metabolism and differentiation using light-mediated signalling pathways; however, its role in neural organoid development remains insufficiently understood. This study investigated the effects of PBM on the differentiation of adipose-derived mesenchymal stem cells (ADMSCs) into neuronal organoid-like structures using a 3D culture system. Immortalized ADMSCs were exposed to 525&#xa0;nm and 825&#xa0;nm wavelengths, individually and in combination, at fluences of 5 and 10&#xa0;J/cm<sup>2</sup>. PBM’s effects were assessed using morphological assessment, cell viability, ATP-based metabolic activity, mitochondrial membrane potential (ΔΨm), and neural gene expression. PBM treatment affected organoid morphology, metabolic activity, and mitochondrial function in a dose- and wavelength-dependent way. Low-fluence irradiation (5&#xa0;J/cm<sup>2</sup>), especially at 525&#xa0;nm, promotes stem cell maintenance and early neural development, as evidenced by enhanced expression of progenitor and neuronal markers. Higher fluence (10&#xa0;J/cm<sup>2</sup>) inhibited early differentiation responses, but mixed wavelength therapy promoted late-stage neuronal maturation with increased <i>RBFOX3</i> gene expression. These findings indicate PBM as a viable method for controlling stem cell destiny and improving neuronal organoid formation for neuroregenerative applications.</p>

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Photobiomodulation-induced Differentiation of Adipose-derived Stem Cells into Neuronal Organoid-like Structures

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月1日

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  • Precious Earldom Mulaudzi,
  • Heidi Abrahamse,
  • Anine Crous

摘要

The ability to regulate stem cell differentiation into organized neural tissue remains a major challenge in regenerative medicine, particularly in the development of physiologically relevant three-dimensional (3D) organoid models. Photobiomodulation (PBM) is a new non-invasive technology for controlling cellular metabolism and differentiation using light-mediated signalling pathways; however, its role in neural organoid development remains insufficiently understood. This study investigated the effects of PBM on the differentiation of adipose-derived mesenchymal stem cells (ADMSCs) into neuronal organoid-like structures using a 3D culture system. Immortalized ADMSCs were exposed to 525 nm and 825 nm wavelengths, individually and in combination, at fluences of 5 and 10 J/cm2. PBM’s effects were assessed using morphological assessment, cell viability, ATP-based metabolic activity, mitochondrial membrane potential (ΔΨm), and neural gene expression. PBM treatment affected organoid morphology, metabolic activity, and mitochondrial function in a dose- and wavelength-dependent way. Low-fluence irradiation (5 J/cm2), especially at 525 nm, promotes stem cell maintenance and early neural development, as evidenced by enhanced expression of progenitor and neuronal markers. Higher fluence (10 J/cm2) inhibited early differentiation responses, but mixed wavelength therapy promoted late-stage neuronal maturation with increased RBFOX3 gene expression. These findings indicate PBM as a viable method for controlling stem cell destiny and improving neuronal organoid formation for neuroregenerative applications.