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  4. Small Molecules Temporarily Induce Neuronal Features in Adult Canine Dermal Fibroblasts

Small Molecules Temporarily Induce Neuronal Features in Adult Canine Dermal Fibroblasts

Int. J. Mol. Sci., 2023 · DOI: 10.3390/ijms242115804 · Published: October 31, 2023

GeneticsVeterinary Medicine

Simple Explanation

Researchers are looking for easier ways to create neurons for therapies and research, especially for canine models that mimic human nerve diseases. They've found that certain small molecules can change skin cells (fibroblasts) into cells with neuron-like characteristics, offering a potential shortcut compared to more complex methods. This study explored whether adult canine skin cells could be converted into neuron-like cells using a combination of small molecules. The goal was to see if this method could provide a practical source of neurons for studying and treating nerve damage in dogs, which often serve as models for human conditions. The research showed that while small molecules could indeed induce neuron-like features in canine skin cells, these changes were temporary. This means further work is needed to make the conversion more stable and useful for long-term therapies.

Study Duration
Not specified
Participants
Nine beagle dogs
Evidence Level
Not specified

Key Findings

  • 1
    Adult canine dermal fibroblasts (ACDFs) treated with eight small molecules (SMs) developed neuron-like morphology, including a round-shaped cell body with branching processes.
  • 2
    Transcriptome profiling revealed the upregulation of neuron-related genes (e.g., SNAP25, GRIA4) and downregulation of fibroblast-related genes (e.g., COL12A1, CCN5) in SM-treated ACDFs.
  • 3
    Neuronal features induced by SMs in ACDFs were temporary, as they diminished after culturing without SMs or after in vivo transplantation into an injured spinal cord.

Research Summary

This study aimed to induce neuronal features in adult canine dermal fibroblasts (ACDFs) using small molecules (SMs) and to assess the permanency of these changes, addressing the need for efficient neuronal reprogramming methods in canine cells, which are relevant as models for human central nerve diseases. The researchers found that SMs can induce neuronal morphology, protein expression (MAP2, βIII-tubulin, NF-M), and activity (Ca2+ influx) in ACDFs, along with the upregulation of neuron-related genes and downregulation of fibroblast-related genes. However, the induced neuronal features were temporary, as they diminished upon removal of SMs in 2D and 3D cultures, as well as in vivo transplantation into an injured spinal cord, highlighting the need for further optimization to achieve stable and permanent neuronal conversion.

Practical Implications

Regenerative Therapy Potential

The study contributes to the development of cell replacement and transplantation therapies for nerve injuries, offering insights into converting readily available cells into neurons.

Drug Screening and Development

The induced neuronal features in ACDFs can be used to screen drugs targeting neurological disorders, providing a relevant model for canine-specific and potentially human-relevant drug responses.

Understanding Reprogramming Barriers

The finding that neuronal induction is temporary highlights the need to overcome epigenetic and other barriers to achieve stable neuronal conversion, informing future research directions.

Study Limitations

  • 1
    The study did not assess the neuronal induction efficacy with increasing age of canine donors.
  • 2
    Additional electrophysiological evaluation is needed to reliably assess neuronal function.
  • 3
    Further optimization of the induction process is necessary to achieve highly efficient conversion of ACDFs to neurons.

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