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Adult mesenchymal stem cells support cisplatin-treated dorsal root ganglion survival
Arianna Scuteri1, Elisabetta Donzelli, Maddalena Ravasi
1Dipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca, Via Cadore 48, 20052 Monza, Italy. arianna.scuteri@unimib.it
Abstract:
Mesenchymal stem cells (MSCs) have been found to be useful in the management of different models of neurological diseases. In the present study, we tested the possible protective effect of MSCs on sensory dorsal root ganglia (DRG) explants exposed to the toxic effect of CDDP, a widely used anticancer drug. DRG explants cultured on a collagen layer and exposed to NGF for 2h (differentiating neurons) or for 5 days (fully differentiated neurons) were treated with CDDP and subsequently co-cultured with MSCs. MSCs were able to support the survival of both differentiating and fully differentiated DRG neurons up to 2 months after the drug treatment, reducing the CDDP-induced death of DRG neurons. MSCs were, however, unable to restore the correct length of DRG neurites compromised by CDDP treatment. The positive effect on neuronal survival was exerted through the contact between DRG and MSCs, and not mediated by neurotrophic factors released by the MSCs. Our observations could represent a starting point for designing a neuroprotective strategy to limit CDDP induced neuropathy without interfering with its anticancer properties.
Insights
Mesenchymal stem cells (MSCs) protect sensory neurons from chemotherapy drug damage. MSCs enhance neuron survival but do not restore nerve length, offering a potential neuroprotective strategy.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Mesenchymal stem cells (MSCs) show promise in neurological disease models.
- Chemotherapy drugs like CDDP can cause neurotoxicity, particularly affecting dorsal root ganglia (DRG) neurons.
- Developing strategies to mitigate chemotherapy-induced neuropathy is crucial for patient care.
Purpose of the Study:
- To investigate the neuroprotective potential of MSCs against CDDP-induced toxicity in sensory DRG neurons.
- To determine if MSCs can support the survival and neurite integrity of DRG neurons exposed to CDDP.
- To elucidate the mechanism underlying MSC-mediated neuroprotection.
Main Methods:
- DRG explants (both differentiating and fully differentiated neurons) were cultured and exposed to CDDP.
- Explants were subsequently co-cultured with MSCs.
- Neuronal survival and neurite length were assessed up to two months post-treatment.
- The role of cell contact versus secreted factors was investigated.
Main Results:
- MSCs significantly enhanced the survival of DRG neurons treated with CDDP for up to two months.
- MSCs did not restore the CDDP-induced shortening of DRG neurites.
- The neuroprotective effect of MSCs was mediated by direct cell-to-cell contact, not by secreted neurotrophic factors.
Conclusions:
- MSCs offer a viable neuroprotective strategy against CDDP-induced DRG neuron death.
- MSC-mediated neuroprotection relies on physical contact rather than paracrine signaling.
- This finding opens avenues for developing treatments that reduce chemotherapy-induced neuropathy without compromising anticancer efficacy.
