Header

UZH-Logo

Maintenance Infos

Clonal dominance and transplantation dynamics in hematopoietic stem cell compartments


Ashcroft, Peter; Manz, Markus G; Bonhoeffer, Sebastian (2017). Clonal dominance and transplantation dynamics in hematopoietic stem cell compartments. PLoS Computational Biology, 13(10):e1005803.

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.

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.

Statistics

Altmetrics

Downloads

4 downloads since deposited on 30 Oct 2017
4 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Hematology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:9 October 2017
Deposited On:30 Oct 2017 15:08
Last Modified:09 Dec 2017 03:05
Publisher:Public Library of Science (PLoS)
ISSN:1553-734X
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1371/journal.pcbi.1005803
PubMed ID:28991922

Download

Download PDF  'Clonal dominance and transplantation dynamics in hematopoietic stem cell compartments'.
Preview
Content: Published Version
Language: English
Filetype: PDF
Size: 5MB
View at publisher
Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)