Generation of mesenchymal stem cells from induced pluripotent stem cells for use in periodontal regeneration (#125)
Mesenchymal stem cells (MSCs) have received significant attention in recent years due to their suitability for use in regenerative medicine. The vast therapeutic potential of MSCs has however highlighted the need for identifying easily accessible and reliable sources of these cells. Current procedures for obtaining MSCs are invasive, expensive and laborious. An attractive alternative source for obtaining large populations of MSCs is through controlled differentiation of readily expandable induced pluripotent stem cells (iPSCs).
We have establish a protocol for inducing human iPSCs to differentiate into MSCs. We generated MSCs by differentiating iPS cells in MSC media for two weeks followed by serial passaging to select for fast growing MSC like cells which have the capacity to attach and proliferate in mono-layer cultures, whilst eliminating slow-growing differentiating iPS cells. We have successfully generated MSC like cells from iPS cell lines derived from three different somatic tissues; gingiva, periodontal ligament, and foreskin. The resulting MSC like cells generated express key mesenchymal stem cell markers including: CD73, CD90 and CD105. In vitro differentiation revealed the MSC like cells have the capacity to differentiate into cementoblast-like cells, adipocytes and collagen-forming cells.
Finally we have performed a pilot study to assess if the MSC like cells generated were able to contribute to periodontal tissue repair. We transplanted the MSC like cells into surgically created periodontal defects in immune-compromised rats. Initial results indicate that the MSC like cells contributed to the enhanced level of regeneration seen in rats which received the MSC like cells when compared to control rats.
Together our findings demonstrate that MSC like cells can be generated from iPS cells and could provide a novel and unlimited source of MSC cells which will be much safer for use in periodontal regenerative therapy.