The success of stem cell transplantations and the potential post-transplantation complications may be dependent, among other factors, on the capacity of the recipient and the transplanted cells to repair DNA damage

Lewis Reynolds

doi:10.3897/biodiscovery.19.e9076

Abstract

Cell therapy is presently a treatment of choice for many types of haematological and metabolic diseases and is likely to become a therapeutic option for other severe human diseases and conditions in the near future. The success of cell transplantation depends on a variety of factors, including the degree of HLA match between the donor and the recipient, the infectious burden of the graft, cell dosage, age, general state of the recipient and other incompletely characterised features of the donor and the recipient. It is likely that the individual capacity for identification and repair of DNA damage and maintenance of genomic integrity may account, at least in part, for these elusive factors that modulate transplantation outcome in terms of success rate and both long and short term post-transplantation complications. This paper outlines the role of individual repair capacity of the donor and recipient in cell transplantations, summarising the little knowledge already accumulated in the field whilst analysing the known major issues of the use of different types of stem cells. Attention will be given to their capacity to maintain the integrity of their genome, the ability to renew their own population, differentiate into various cell types and in some cases, succumb to carcinogenic transformation. Analysis of the individual capacity may become a useful tool in the assessment of the suitability of a set of freshly collected stem cells or an in vitro propagated cell line for potential clinical applications.

Highlights

The Discovery of Individual Repair CapacityIn the last third of the 20th century, DNA repair proved itself as a fundamental process in living cells, probably no less important as the triad of replication, transcription and translation that made up the famous central dogma of molecular biology as formulated by Francis Crick in 1970
N Reynolds L some cases, succumb to carcinogenic transformation
Autologous haematopoietic stem cells (HSCs) transplantations are not recommended for most types of leukaemia, with the possible exception of patients with acute myeloid leukaemia placed in the "favourable" and

Summary

The Discovery of Individual Repair Capacity

In the last third of the 20th century, DNA repair proved itself as a fundamental process in living cells, probably no less important as the triad of replication, transcription and translation that made up the famous central dogma of molecular biology as formulated by Francis Crick in 1970. After it became clear that a molecular defect in a single gene coding for a protein functioning in DNA repair could be associated with severe early-onset systemic disease (CLEAVER 1968), and later, that inherited defects in the tumoursuppressor gene RB1 were associated with development of retinoblastoma (Fung et al 1987), it was believed that all genetic alterations that affected genes of DNA damage detection and repair had immediate adverse effects on the phenotype. This meant that there could be very little degree of polymorphism in genes coding for proteins of DNA repair and maintenance of genomic integrity.

The Role of IRC as a Factor Determining the Outcome of HSC

Findings

Conclusions