Transient arrest of cell ageing during amplification of human cells in culture

Project description

Project Summary

One of the strategies that we are currently using to investigate tissue replacement for dental pulps involves seeding cells into inert scaffolds made from biocompatible materials. However, amplification of dental pulp cells to provide a sufficient population size for establishing a synthetic pulp results in the propagation of an aged cell population that is unsuitable for use in dental pulp tissue replacement.

In our previous studies, we have confirmed that human dental pulp (hDPCs) cells undergo chromosomal attrition and usually reach cell senescence by cell passage 12. Analysis of the telomeres in such amplified populations suggests a telomere attrition rate of 0.4-0.5kb per generation. In order to overcome this problem we have used synthetic telomere linker oligonucleotides for rescuing human dental pulp cells (hDPCs) from ageing associated with the “end replication problem”. One such linker oligonucleotide, “telome 3”, was found to arrest ageing in hDPCs, as judged by cell viability and total cell numbers, in a reproducible manner. Since current methods for measuring telomere length are either clumsy, inaccurate or both, we are investigating novel approaches to measuring telomere length as a guide to determining rates of cell ageing.

Aims and Objectives

The aim of the proposed research is to investigate the potential of delivering optimum oligonucleotides such as “telome 3’ to arrest hDPSCs ageing and whether this effect is transient and controllable. Other cell types may also be used as the control to look at if this arrest is a general phenomenon or is restricted to hDPCs. Moreover, the mechanism of delivery method will also be investigated, which may provide insight into future strategies for gene delivery. The novel methods for measuring telomere length will be further optimised in order to measure the length of individual telomeres. This would open up a whole new avenue to investigate the possibility that ageing is controlled by the attrition of specific chromosomes.

Entry requirements

Please contact our staff for further details about entry requirements.

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How to apply (phone)

+44 (0)113 343 7497