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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Recent Advances in Neuronal-like Differentiation of Mesenchymal Stem/Stromal Cells

  1. 1Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
  2. 2Department of Medicine and Surgery, University of Enna “Kore”, 94100 Enna, Italy
  3. 3Chi.Pla Chirurgia Plastica, Via Suor Maria Mazzarello, 54, 95128 Catania, Italy

Abstract

Mesenchymal stem/stromal cells (MSCs) have been widely investigated in recent decades because of their multipotent differentiation abilities. In fact, MSCs are able to differentiate not only into mesodermal cell lines (adipocytes, chondrocytes, osteocytes), but also into neuronal and glial cells. MSCs can be derived from different sources, such as bone marrow, adipose tissue, peripheral blood and various neonatal birth-associated tissues. They are suitable candidate in cell-based approaches for both autologous and heterologous transplantation in the field of regenerative medicine. Unlike other types of stem cells, MSCs raise no ethical issues and feature low risks of tumorigenesis after transplantation into humans or animals. In addition, they may exert beneficial effects due to their paracrine actions which help tissue recovery. Numerous studies describe effects obtained following MSC treatments in a variety of human pathologies, including nervous system diseases. The nervous tissue is characterized by very limited recovery properties, likely because of a scarce presence of stem cell niches, which are confined to the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. These niches cannot be able to counteract the neuronal loss after damage or degenerative events. Many efforts have been made to obtain functional neuronal differentiated MSCs to be used for transplantation. However, evidence of complete neuronal maturation and functional integration of neuronal-like MSCs remains limited, and clinical studies have used undifferentiated MSCs rather than neuronal-like cell populations. In this review, we mainly focus on various differentiation protocols that have been adopted for in vitro studies, taking also into account the underlying pathways involved.

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BibTeX
@article{romano2026recent,
  title = {{Recent Advances in Neuronal-like Differentiation of Mesenchymal Stem/Stromal Cells}},
  author = {Ivana Roberta Romano and Floriana D’angeli and Grazia Maugeri and Giuseppe Musumeci and Serena Tamburino and Giuseppe Angelo Giovanni Lombardo and Rosario Giuffrida and Giuliana Mannino and Debora Lo Furno},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = nov,
  doi = {10.3390/ijms27219902},
  url = {https://www.mdpi.com/1422-0067/27/21/9902},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Recent Advances in Neuronal-like Differentiation of Mesenchymal Stem/Stromal Cells
AU  - Ivana Roberta Romano
AU  - Floriana D’angeli
AU  - Grazia Maugeri
AU  - Giuseppe Musumeci
AU  - Serena Tamburino
AU  - Giuseppe Angelo Giovanni Lombardo
AU  - Rosario Giuffrida
AU  - Giuliana Mannino
AU  - Debora Lo Furno
PY  - 2026
DA  - 2026/11/05
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219902
UR  - https://www.mdpi.com/1422-0067/27/21/9902
AB  - Mesenchymal stem/stromal cells (MSCs) have been widely investigated in recent decades because of their multipotent differentiation abilities. In fact, MSCs are able to differentiate not only into mesodermal cell lines (adipocytes, chondrocytes, osteocytes), but also into neuronal and glial cells. MSCs can be derived from different sources, such as bone marrow, adipose tissue, peripheral blood and various neonatal birth-associated tissues. They are suitable candidate in cell-based approaches for both autologous and heterologous transplantation in the field of regenerative medicine. Unlike other types of stem cells, MSCs raise no ethical issues and feature low risks of tumorigenesis after transplantation into humans or animals. In addition, they may exert beneficial effects due to their paracrine actions which help tissue recovery. Numerous studies describe effects obtained following MSC treatments in a variety of human pathologies, including nervous system diseases. The nervous tissue is characterized by very limited recovery properties, likely because of a scarce presence of stem cell niches, which are confined to the dentate gyrus of the hippocampus and the subventricular zone of the lateral ventricles. These niches cannot be able to counteract the neuronal loss after damage or degenerative events. Many efforts have been made to obtain functional neuronal differentiated MSCs to be used for transplantation. However, evidence of complete neuronal maturation and functional integration of neuronal-like MSCs remains limited, and clinical studies have used undifferentiated MSCs rather than neuronal-like cell populations. In this review, we mainly focus on various differentiation protocols that have been adopted for in vitro studies, taking also into account the underlying pathways involved.
SN  - 1422-0067
ER  -