iPS cell technology for periodontal tissue regeneration

Abstract

Stem cells are proliferative and can develop into other types of specific organ cell. They are responsible for the embryo’s ability to develop normally and enable the human body to heal wounds, grow and replace cells lost daily through wear and tear or disease. There are different types of stem cell, with mesenchymal cells (MSCs) having been identified as the most useful in adults. Clinical studies have shown that infusions of mesenchymal cells can induce healing, without any noted side effects or increased cancer risk. Mesenchymal cells can be extracted from embryos or adult human tissue, including bone marrow, fat and skin. MSCs can also be isolated from orofacial tissue including dental pulp, immature teeth within gums and the periodontal ligament. Bone marrow or dental-origin MSCs have the additional advantage of possessing immunosuppressive properties, which makes them less likely to be rejected and more efficacious for tissue repair. There have been a number of clinical studies of orofacial-source MSC transplantations in small and large animals and humans, which demonstrate their ability to differentiate into the different types of periodontal tissue, including bone, ligament and cementum. However, as Ouchi says: ‘In cases of severe periodontal disease, the periodontal ligament has been eroded and many of the other orofacial sources of MSCs can be degraded. Also, this approach requires a separate operation to extract a tiny proportion of MSCs, which must be cultured and processed prior to reinjection at the sites of damage, or a more intrusive operation to extract bone marrow.’ Ouchi explains: ‘In order to avoid separate surgical operations and to produce a large amount of MSCs in a cost-effective manner, we wanted to find a way of inducing appropriate MSCs for periodontal repair, from adult-sourced induced pluripotent stem cells, following established protocols.’ He adds: ‘We have shown in earlier work that the MSCs most potent for dental tissue regeneration express specific markers, particularly for low affinity nerve growth factor receptor (LNGFR).’ By following the work of other research groups, the team isolated and purified batches of MSCs, but it was found that these were very heterogenous, with few expressing the LNGFR marker. Ouchi and his team considered that they needed to go back to basics and think about the embryonic origins of orofacial MSCs and how iPS cells could be induced to follow this specific developmental pattern.