Clonal Dominance and Transplantation Dynamics in Hematopoietic Stem Cell Compartments

TL;DR

This paper develops a mathematical model of hematopoietic stem cell migration between bone marrow and blood, analyzing clonal dynamics and transplantation outcomes to inform treatment strategies.

Contribution

It introduces a novel individual-based model of stem cell migration and engraftment, providing quantitative insights into clonal hematopoiesis and transplantation dynamics.

Findings

Quantifies migration rates between bone marrow and blood.

Predicts clone expansion times and chimerism levels.

Analyzes impact of conditioning on engraftment success.

Abstract

Hematopoietic stem cells in mammals are known to reside mostly in the bone marrow, but also transitively passage in small numbers in the blood. Experimental findings have suggested that they exist in a dynamic equilibrium, continuously migrating between these two compartments. Here we construct an individual-based mathematical model of this process, which is parametrised using existing empirical findings from mice. This approach allows us to quantify the amount of migration between the bone marrow niches and the peripheral blood. We use this model to investigate clonal hematopoiesis, which is a significant risk factor for hematologic cancers. We also analyse the engraftment of donor stem cells into non-conditioned and conditioned hosts, quantifying the impact of different treatment scenarios. The simplicity of the model permits a thorough mathematical analysis, providing deeper insights into the dynamics of both the model and of the real-world system. We predict the time taken for mutant clones to expand within a host, as well as chimerism levels that can be expected following transplantation therapy, and the probability that a preconditioned host is reconstituted by donor cells.