Ultrasound‐Responsive Polymeric Piezoelectric Nanoparticles for Remote Activation and Neuronal Differentiation of Human Neural Stem Cells
The regenerative capacity of the central nervous system (CNS) is limited. Understanding and enhancing the mechanisms that induce neural differentiation of neural stem cells (NSCs) is crucial for advancing regenerative medicine; one significant challenge in this effort is the remote delivery of pro‐d...
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Wiley-VCH
2025-02-01
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| Online Access: | https://doi.org/10.1002/smsc.202400354 |
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| author | Arianna Bargero Matteo Battaglini Tommaso Curiale Alessio Carmignani Margherita Montorsi Massimiliano Labardi Carlotta Pucci Attilio Marino Gianni Ciofani |
| author_facet | Arianna Bargero Matteo Battaglini Tommaso Curiale Alessio Carmignani Margherita Montorsi Massimiliano Labardi Carlotta Pucci Attilio Marino Gianni Ciofani |
| author_sort | Arianna Bargero |
| collection | DOAJ |
| description | The regenerative capacity of the central nervous system (CNS) is limited. Understanding and enhancing the mechanisms that induce neural differentiation of neural stem cells (NSCs) is crucial for advancing regenerative medicine; one significant challenge in this effort is the remote delivery of pro‐differentiation cues. In this framework, a nanotechnology‐based solution able to remotely trigger the differentiation of human NSCs (hNSCs) into neurons is proposed. The approach involves organic piezoelectric nanotransducers, which can be remotely activated by low‐intensity ultrasound (US) for local and noninvasive electrical stimulation. Highly biocompatible piezoelectric polymeric nanoparticles, when activated by US, demonstrate the ability to induce calcium influx, exit from the cell cycle, and neuronal differentiation in hNSCs, as evidenced by calcium imaging experiments and the expression analysis of the NeuN post‐mitotic neural marker; additionally, an increased outgrowth of the developing axons is observed. Gene expression analysis moreover suggests that the neural differentiation mechanism induced by piezoelectric stimulation acts by upregulating the calcium signaling‐sensitive NeuroD1 neural inducer and the Lamb1 marker, independently of the c‐Jun/c‐Fos pathway. Considering the high biocompatibility and the good piezoelectricity of the polymeric nanotransducers used in this work, it is believed that this “wireless” stimulation approach holds high potential in CNS regenerative medicine. |
| format | Article |
| id | doaj-art-4c3666cd1e1b4d24a2d5003a2d6ea656 |
| institution | DOAJ |
| issn | 2688-4046 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Small Science |
| spelling | doaj-art-4c3666cd1e1b4d24a2d5003a2d6ea6562025-08-20T03:04:47ZengWiley-VCHSmall Science2688-40462025-02-0152n/an/a10.1002/smsc.202400354Ultrasound‐Responsive Polymeric Piezoelectric Nanoparticles for Remote Activation and Neuronal Differentiation of Human Neural Stem CellsArianna Bargero0Matteo Battaglini1Tommaso Curiale2Alessio Carmignani3Margherita Montorsi4Massimiliano Labardi5Carlotta Pucci6Attilio Marino7Gianni Ciofani8Istituto Italiano di Tecnologia Smart Bio‐Interfaces Viale Rinaldo Piaggio 34 56025 Pontedera ItalyIstituto Italiano di Tecnologia Smart Bio‐Interfaces Viale Rinaldo Piaggio 34 56025 Pontedera ItalyIstituto Italiano di Tecnologia Smart Bio‐Interfaces Viale Rinaldo Piaggio 34 56025 Pontedera ItalyIstituto Italiano di Tecnologia Smart Bio‐Interfaces Viale Rinaldo Piaggio 34 56025 Pontedera ItalyIstituto Italiano di Tecnologia Smart Bio‐Interfaces Viale Rinaldo Piaggio 34 56025 Pontedera ItalySede Secondaria di Pisa CNR‐IPCF Largo Pontecorvo 3 56127 Pisa ItalyIstituto Italiano di Tecnologia Smart Bio‐Interfaces Viale Rinaldo Piaggio 34 56025 Pontedera ItalyIstituto Italiano di Tecnologia Smart Bio‐Interfaces Viale Rinaldo Piaggio 34 56025 Pontedera ItalyIstituto Italiano di Tecnologia Smart Bio‐Interfaces Viale Rinaldo Piaggio 34 56025 Pontedera ItalyThe regenerative capacity of the central nervous system (CNS) is limited. Understanding and enhancing the mechanisms that induce neural differentiation of neural stem cells (NSCs) is crucial for advancing regenerative medicine; one significant challenge in this effort is the remote delivery of pro‐differentiation cues. In this framework, a nanotechnology‐based solution able to remotely trigger the differentiation of human NSCs (hNSCs) into neurons is proposed. The approach involves organic piezoelectric nanotransducers, which can be remotely activated by low‐intensity ultrasound (US) for local and noninvasive electrical stimulation. Highly biocompatible piezoelectric polymeric nanoparticles, when activated by US, demonstrate the ability to induce calcium influx, exit from the cell cycle, and neuronal differentiation in hNSCs, as evidenced by calcium imaging experiments and the expression analysis of the NeuN post‐mitotic neural marker; additionally, an increased outgrowth of the developing axons is observed. Gene expression analysis moreover suggests that the neural differentiation mechanism induced by piezoelectric stimulation acts by upregulating the calcium signaling‐sensitive NeuroD1 neural inducer and the Lamb1 marker, independently of the c‐Jun/c‐Fos pathway. Considering the high biocompatibility and the good piezoelectricity of the polymeric nanotransducers used in this work, it is believed that this “wireless” stimulation approach holds high potential in CNS regenerative medicine.https://doi.org/10.1002/smsc.202400354neural differentiationsneural stem cellspiezoelectric nanoparticlesregenerative medicinesultrasound‐responsive nanomaterials |
| spellingShingle | Arianna Bargero Matteo Battaglini Tommaso Curiale Alessio Carmignani Margherita Montorsi Massimiliano Labardi Carlotta Pucci Attilio Marino Gianni Ciofani Ultrasound‐Responsive Polymeric Piezoelectric Nanoparticles for Remote Activation and Neuronal Differentiation of Human Neural Stem Cells Small Science neural differentiations neural stem cells piezoelectric nanoparticles regenerative medicines ultrasound‐responsive nanomaterials |
| title | Ultrasound‐Responsive Polymeric Piezoelectric Nanoparticles for Remote Activation and Neuronal Differentiation of Human Neural Stem Cells |
| title_full | Ultrasound‐Responsive Polymeric Piezoelectric Nanoparticles for Remote Activation and Neuronal Differentiation of Human Neural Stem Cells |
| title_fullStr | Ultrasound‐Responsive Polymeric Piezoelectric Nanoparticles for Remote Activation and Neuronal Differentiation of Human Neural Stem Cells |
| title_full_unstemmed | Ultrasound‐Responsive Polymeric Piezoelectric Nanoparticles for Remote Activation and Neuronal Differentiation of Human Neural Stem Cells |
| title_short | Ultrasound‐Responsive Polymeric Piezoelectric Nanoparticles for Remote Activation and Neuronal Differentiation of Human Neural Stem Cells |
| title_sort | ultrasound responsive polymeric piezoelectric nanoparticles for remote activation and neuronal differentiation of human neural stem cells |
| topic | neural differentiations neural stem cells piezoelectric nanoparticles regenerative medicines ultrasound‐responsive nanomaterials |
| url | https://doi.org/10.1002/smsc.202400354 |
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