Generation of c-MycERTAM-transduced human late-adherent olfactory mucosa cells for potential regenerative applications

Scientific Reports, 2019 · DOI: 10.1038/s41598-019-49315-6 · Published: September 13, 2019

Regenerative Medicine Neurology Genetics

Simple Explanation

The study aimed to create a versatile cell line from human olfactory mucosa cells (hOMCs) that could potentially be used for spinal cord injury (SCI) treatment. The researchers focused on late-adherent hOMCs, which are believed to contain olfactory ensheathing cells (OECs). To achieve this, they used a c-MycERTAM gene that allows the cells to multiply when a specific drug (4-hydroxytamoxifen or 4-OHT) is present. They successfully created two cell populations, PA5 and PA7, and characterized their growth and properties. The PA5 cell population, which showed better growth and stability, was further analyzed. Results showed PA5 cells express markers associated with glial cells, neurons and fibroblasts and they were able to promote neurite outgrowth, suggesting a potential role in nerve regeneration.

Study Duration

60 days

Participants

Two independent mucosal biopsies, named as PA5 and PA7, were obtained following informed consent

Evidence Level

Not specified

Key Findings

1
The study successfully generated two c-MycERTAM-derived hOMC populations (PA5 and PA7) through retroviral transduction. These cells incorporated the c-MycERTAM transgene into their genome and expressed the corresponding protein.
2
PA5 hOMCs exhibited a normal human karyotype and faster growth kinetics compared to PA7 cells. This karyotypic stability and growth advantage led to PA5 being selected for further characterization.
3
Co-culture experiments showed that PA5 hOMCs promote neurite outgrowth in neuronal cell lines (NG108-15) and primary dorsal root ganglion (DRG) neurons, indicating their potential to support neural regeneration.

Research Summary

This study successfully generated and characterized c-MycERTAM-transduced human late-adherent olfactory mucosa cells (hOMCs) for potential regenerative applications in spinal cord injury (SCI). Two polyclonal populations, PA5 and PA7, were derived, with PA5 demonstrating superior growth kinetics and karyotypic stability. PA5 cells expressed glial, neuronal, and fibroblast-associated markers. In vitro co-culture assays revealed that PA5 hOMCs promote neurite outgrowth in neuronal cell lines and primary dorsal root ganglion neurons, suggesting their potential as a regenerative therapy for neural cells.

Practical Implications

Therapeutic potential for SCI

The generated PA5 hOMCs show promise as a cell therapy for spinal cord injury due to their ability to promote neurite outgrowth.

Allogeneic Cell Source

The c-MycERTAM technology enables the expansion of hOMCs, potentially providing an 'off-the-shelf' allogeneic cell source for transplantation, overcoming limitations of autologous approaches.

Development of ATMPs

The study provides a foundation for developing advanced therapy medicinal products (ATMPs) using modified hOMCs for CNS injuries.

Study Limitations

1
The study is limited to in vitro experiments, requiring further in vivo validation to assess functional recovery in animal models of spinal cord injury.
2
Long-term culture may lead to epigenetic silencing of the c-MycERTAM transgene, affecting cell proliferation and requiring further investigation.
3
The safety profile of the gene-modified cells needs to be thoroughly evaluated, including assessing the risk of tumorigenesis.

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