A team of researchers, led by Prof. Jeong Beom Kim (School of Natural Science) at UNIST has announced that they have successfully developed a new technology to produce customized stem cells that can be used towards cell replacement therapy, as well as drug screening in spinal cord injury (SCI) or demyelinating disorders.
The findings appeared in the October 27 edition of the journal of the European Molecular Biology Organization (EMBO).
In this study, the team engineered oligodendrocyte precursor cells (OPCs) by using one particular single gene. OPCs, the nerve cells that make up the insulating myelin sheath around axons. According to the team, the use of this newly developed cell production technology overcomes the limitations of current OPC production methods. In fact, this new cell can not only contribute to myelin repair, but they become activated in response to the treatment of damaged spinal cords.
In contrast to the previously reported three-factor-derived induced oligodendrocyte progenitor cells (iOPCs), Prof. Kim’s team used a minimal number of transcription factors. They employed Oct4-mediated direct reprogramming strategy, which induces cell fate plasticity at the early phase of reprogramming through mediating ectopic expression of Oct4.
Through this study, the team discovered that single-factor-derived iOPCs have higher levels of genomic stability by having lower chance of viral integration into the host genome, thereby reducing the chance of viral insertional mutagenesis.
This research was partly supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) and funded by the ICT R&D Program of Ministry of Science, ICT & Future Planning (MSIP) and Max Planck Partner Group, Max Planck Society (MPG), Germany.
1) Title: Oct4-induced oligodendrocyte progenitor cells enhance functional recovery in spinal cord injury model
2) Authors: Jeong Beom Kim (Corresponding author, Assistant Professor, UNIST), Hyunah Lee (co-author, MS/Ph.D. combined programme, UNIST), Donggyu Nam (co-author, MS programme, UNIST), Myung Rae Park (co-author, Ph.D. programme, UNIST), Seok-Jin Lee (co-author, Post-Doc, UNIST)
3) Summary of research: In this research, iOPC that forms myelin sheath in spinal cord was generated from the terminally differentiated somatic cells by Oct4-mediated direct conversion method. The homogeneous iOPC-cell line expressed OPC-specific markers (A2B5, NG2 and PDGFR-α) and shares very similar gene expression pattern with wild-type OPC. Also, the iOPCs are self-renewing and bipotent cells that differentiate to both astrocytes and myelinating oligodendrocytes in vitro and in vivo. The iOPC showed 90% higher differentiation rate to matured oligodendrocytes than the previously reported OPCs.
4) Future use: The direct conversion strategy that converts somatic cells to OPC can eliminate the risk of tumorigenesis, and the generation of self-renewing stem cells using this strategy enables the large-scale expansion of the target cells that can be used in patient-specific cell therapy or drug screening. Moreover, the generated cells can be used as the cell source for 3D bio-printing the patient specific spinal cord tissue in the future. The iOPC-cell line generated from this research will be developed as the cell therapy products for treating the spinal cord injury and we expect that it will contribute in strengthening the national economy through leading the regenerative medicine market. Moreover, it will also contribute in improving the quality of life through advancing the health care service.