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Roles of Stem Cells in Nerve Regeneration
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Roles of Stem Cells in Nerve Regeneration

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (14 December 2018) | Viewed by 15100

Special Issue Editors

Prof. Dr. Umberto Di Porzio

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Guest Editor
Institute of Genetics and Biophysics “Adriano Buzzati Traverso”, CNR, Naples, Italy
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Gian Carlo Bellenchi

E-Mail Website
Guest Editor
Institute of Genetics and Biophysics “Adriano Buzzati Traverso”, CNR, Naples, Italy

Special Issue Information

Dear Colleagues,

Stem cells, neural or adult mesenchymal or IPSC, have great translational potential and offer a powerful tool for basic research and regenerative medicine.

They have been shown to grow brain organoids to model brain disorders, replace CNS neurons or Schwann cells, improve nerve regeneration, through direct conversion into specific neuronal cell types, capable to be included in existing neural circuits, or into myelinating cell lines. Endogenous or exogenous stem cells exert they potential also through the production of local neurotrophic factors for the sustenance of residual healthy neurons or induction of axonal growth and circuitry restoration.

However, important basic biological questions in regeneration and repair are still unanswered.

We wish to stimulate contributions on stem cell isolation, application in the treatment of various disorders of nerves and the nervous system.

We hope thus to summarize the current state of understanding on the role of stem cells in neurodegeneration and nerve regeneration and help us to focus on effective therapies. To this end, we welcome experts in the field to contribute research papers and critical reviews on the various facets of stem cell-ness including new therapeutic pharmacological strategies.

Prof. Dr. Umberto Di Porzio
Prof. Dr. Gian Carlo Bellenchi
Guest Editors

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Keywords

  • neural stem cells
  • mesenchymal stem cells
  • resident stem cells
  • adult neurogenesis
  • IPSC
  • nerve injury
  • nerve regeneration
  • trophic factors
  • functional remodeling
  • repair

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Published Papers (3 papers)

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Research

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19 pages, 2891 KiB  
Article
Proteomic Analysis of Cyclic Ketamine Compounds Ability to Induce Neural Differentiation in Human Adult Mesenchymal Stem Cells
by Jerran Santos, Bruce Kenneth Milthorpe and Matthew Paul Padula
Int. J. Mol. Sci. 2019, 20(3), 523; https://doi.org/10.3390/ijms20030523 - 26 Jan 2019
Cited by 10 | Viewed by 4149 | Correction
Abstract
Neural regeneration is of great interest due to its potential to treat traumatic brain injuries and diseases that impact quality of life. Growth factor mediated differentiation can take up to several weeks to months to produce the cell of interest whereas chemical stimulation [...] Read more.
Neural regeneration is of great interest due to its potential to treat traumatic brain injuries and diseases that impact quality of life. Growth factor mediated differentiation can take up to several weeks to months to produce the cell of interest whereas chemical stimulation may be as minimal as a few hours. The smaller time scale is of great clinical relevance. Adipose derived stem cells (ADSCs) were treated for up to 24 h with a novel differentiation media containing the cyclic ketamine compounds to direct neurogenic induction. The extent of differentiation was investigated by proteome changes occurring during the process. The treatments indicated the ADSCs responded favorably to the neurogenic induction media by presenting a number of morphological cues of neuronal phenotype previously seen and a higher cell population post induction compared to previous studies. Furthermore, approximately 3500 proteins were analyzed and identified by mass spectrometric iTRAQ analyses. The bioinformatics analyses revealed hundreds of proteins whose expression level changes were statistically significant and biologically relevant to neurogenesis and annotated as being involved in neurogenic development. Complementing this, the Bioplex cytokine assay profiles present evidence of decreased panel of stress response cytokines and a relative increase in those involved in neurogenesis. Full article
(This article belongs to the Special Issue Roles of Stem Cells in Nerve Regeneration)
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12 pages, 4550 KiB  
Article
Cellular and Molecular Mechanisms Mediated by recPrPC Involved in the Neuronal Differentiation Process of Mesenchymal Stem Cells
by Stefano Martellucci, Costantino Santacroce, Francesca Santilli, Luca Piccoli, Simona Delle Monache, Adriano Angelucci, Roberta Misasi, Maurizio Sorice and Vincenzo Mattei
Int. J. Mol. Sci. 2019, 20(2), 345; https://doi.org/10.3390/ijms20020345 - 16 Jan 2019
Cited by 29 | Viewed by 4378
Abstract
Human Dental Pulp Stem Cells (hDPSCs) represent a type of adult mesenchymal stem cells that have the ability to differentiate in vitro in several lineages such as odontoblasts, osteoblasts, chondrocytes, adipocytes and neurons. In the current work, we used hDPSCs as the experimental [...] Read more.
Human Dental Pulp Stem Cells (hDPSCs) represent a type of adult mesenchymal stem cells that have the ability to differentiate in vitro in several lineages such as odontoblasts, osteoblasts, chondrocytes, adipocytes and neurons. In the current work, we used hDPSCs as the experimental model to study the role of recombinant prion protein 23–231 (recPrPC) in the neuronal differentiation process, and in the signal pathway activation of ERK 1/2 and Akt. We demonstrated that recPrPC was able to activate an intracellular signal pathway mediated by extracellular-signal-regulated kinase 1 and 2 (ERK 1/2) and protein kinase B (Akt). Moreover, in order to understand whether endogenous prion protein (PrPC) was necessary to mediate the signaling induced by recPrPC, we silenced PrPC, demonstrating that the presence of endogenous PrPC was essential for ERK 1/2 and Akt phosphorylation. Since endogenous PrPC is a well-known lipid rafts component, we evaluated the role of these structures in the signal pathway induced by recPrPC. Our results suggest that lipid rafts integrity play a key role in recPrPC activity. In fact, lipid rafts inhibitors, such as fumonisin B1 and MβCD, significantly prevented ERK 1/2 and Akt phosphorylation induced by recPrPC. In addition, we investigated the capacity of recPrPC to induce hDPSCs neuronal differentiation process after long-term stimulation through the evaluation of typical neuronal markers expression such as B3-Tubulin, neurofilament-H (NFH) and growth associated protein 43 (GAP43). Accordingly, when we silenced endogenous PrPC, we observed the inhibition of neuronal differentiation induced by recPrPC. The combined data suggest that recPrPC plays a key role in the neuronal differentiation process and in the activation of specific intracellular signal pathways in hDPSCs. Full article
(This article belongs to the Special Issue Roles of Stem Cells in Nerve Regeneration)
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Review

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22 pages, 362 KiB  
Review
Do Neural Stem Cells Have a Choice? Heterogenic Outcome of Cell Fate Acquisition in Different Injury Models
by Felix Beyer, Iria Samper Agrelo and Patrick Küry
Int. J. Mol. Sci. 2019, 20(2), 455; https://doi.org/10.3390/ijms20020455 - 21 Jan 2019
Cited by 9 | Viewed by 5971
Abstract
The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon [...] Read more.
The adult mammalian central nervous system (CNS) is generally considered as repair restricted organ with limited capacities to regenerate lost cells and to successfully integrate them into damaged nerve tracts. Despite the presence of endogenous immature cell types that can be activated upon injury or in disease cell replacement generally remains insufficient, undirected, or lost cell types are not properly generated. This limitation also accounts for the myelin repair capacity that still constitutes the default regenerative activity at least in inflammatory demyelinating conditions. Ever since the discovery of endogenous neural stem cells (NSCs) residing within specific niches of the adult brain, as well as the description of procedures to either isolate and propagate or artificially induce NSCs from various origins ex vivo, the field has been rejuvenated. Various sources of NSCs have been investigated and applied in current neuropathological paradigms aiming at the replacement of lost cells and the restoration of functionality based on successful integration. Whereas directing and supporting stem cells residing in brain niches constitutes one possible approach many investigations addressed their potential upon transplantation. Given the heterogeneity of these studies related to the nature of grafted cells, the local CNS environment, and applied implantation procedures we here set out to review and compare their applied protocols in order to evaluate rate-limiting parameters. Based on our compilation, we conclude that in healthy CNS tissue region specific cues dominate cell fate decisions. However, although increasing evidence points to the capacity of transplanted NSCs to reflect the regenerative need of an injury environment, a still heterogenic picture emerges when analyzing transplantation outcomes in injury or disease models. These are likely due to methodological differences despite preserved injury environments. Based on this meta-analysis, we suggest future NSC transplantation experiments to be conducted in a more comparable way to previous studies and that subsequent analyses must emphasize regional heterogeneity such as accounting for differences in gray versus white matter. Full article
(This article belongs to the Special Issue Roles of Stem Cells in Nerve Regeneration)
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