Cell Rejuvenation Technology Using Transient Expression of Trophoblast Stem Cell Reprogramming Transcription Factors

Almost all cells experience aging, a progressive decline in functionality, leading to tissue dysfunction and disease. At the cellular level, it is associated with reduced function, altered gene expression, and most importantly epigenetic changes.

Converting somatic cells to induced pluripotent stem cells (iPSCs) or induced trophoblast stem cells (iTSCs) can reverse those age-associated changes. However, during the reprogramming process, cell identity is lost, and it can be difficult to reacquire it, as re-differentiated iPSCs often resemble fetal rather than mature adult cells.

In this project, I aim to use transient expression of TSC reprogramming factors in order to achieve human cell rejuvenation. We wish to find the balance between reversing age-related processes and keeping the cell identity and function.
Firstly, I aim to demonstrate the capability of TSC reprogramming transcription factors to partially rejuvenate human elderly fibroblasts and to improve their overall function. I will confirm cell rejuvenation by assessing the expression of aging-related gene markers, epigenetic age, telomere length and improved cell function. Secondly, I will apply the same technology on human CD34+ cells and mouse RPE cells.

Rejuvenation of these cell types has a lot of potential applications – from anti-aging in case of fibroblasts, through bone marrow transplantation and preventive medicine affected by the immune system in CD34+, until preventing AMD in RPE.