Human nasal olfactory stem cells, puriﬁed as advanced therapy medicinal products, improve neuronal differentiation

Frontiers in Neuroscience, 2022 · DOI: 10.3389/fnins.2022.1042276 · Published: November 17, 2022

Simple Explanation

This study focuses on olfactory ecto-mesenchymal stem cells (OE-MSCs) derived from the nasal mucosa, known for their neurogenic and immunomodulatory properties. The aim was to develop a culture protocol meeting health agency standards and to assess the stem cells' effectiveness in promoting neuron differentiation. The researchers compared different methods for purifying and cultivating these stem cells, including enzymatic digestion versus explant culture, and the use of platelet lysate versus fetal calf serum. They also evaluated the impact of OE-MSC conditioned media on the differentiation of neuroblastoma cells into neurons. The study concluded that enzymatic digestion is more efficient for obtaining higher cell numbers, and platelet lysate promotes better cell proliferation compared to fetal calf serum. The OE-MSC conditioned medium also promoted the differentiation of neuroblastoma cells into neurons.

Study Duration

Not specified

Participants

Five healthy adult individuals undergoing a turbinoplasty or a septoplasty

Evidence Level

Not specified

Key Findings

1
Enzymatic digestion yields higher cell numbers more rapidly compared to explant culture-based methods.
2
Platelet lysate is more effective than fetal calf serum in promoting cell proliferation, with an optimal percentage of 10%.
3
Conditioned medium from purified OE-MSCs promotes cell differentiation of Neuro2a neuroblastoma cells.

Research Summary

The study aimed to develop a safer and more efficient manufacturing process for clinical-grade olfactory stem cells, in line with the requirements of human health agencies for advanced therapy medicinal products (ATMP). The researchers found that enzymatic digestion provides a higher number of cells more rapidly than the explant culture method, and platelet lysate is a more potent inducer of cell proliferation compared to fetal calf serum. The study also demonstrated that the conditioned medium of purified OE-MSCs promotes the differentiation of neuroblastoma cells into neurons, suggesting a potential therapeutic application for these stem cells.

Practical Implications

Clinical Translation

The developed protocol allows for the production of clinical-grade OE-MSCs, suitable for use in Phase I clinical trials for nerve injury repair.

Improved Cell Culture

The findings support the use of enzymatic digestion and platelet lysate for more efficient and safer stem cell culture.

Therapeutic Potential

OE-MSC-conditioned medium shows promise as a therapeutic agent for promoting neuronal differentiation and regeneration.

Study Limitations

1
Further studies are required to unveil the underlying mechanisms of action.
2
Banking is necessary in clinical practice to provide therapeutic treatments during the acute phase of injury. This implies testing the eﬃcacy of frozen and thawed OE-MSC-conditioned media.
3
we only tested a single administration of the conditioned medium. However, nerve regeneration is a long process and repeated administrations may be beneﬁcial.

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