HSC Niche Dynamics in Regeneration, Pre-malignancy, and Cancer: Insights From Mathematical Modeling

Overview

Journal Stem Cells

Publisher Oxford University Press

Specialties Cell Biology
Reproductive Medicine

Date 2022 Nov 13

PMID 36371719

Authors

Rasmus Kristoffer Pedersen

Morten Andersen

Vibe Skov

Lasse Kjaer

Hans C Hasselbalch

Johnny T Ottesen

Thomas Stiehl

Affiliations

Soon will be listed here.

Abstract

The hematopoietic stem cell (HSC) niche is a crucial driver of regeneration and malignancy. Its interaction with hematopoietic and malignant stem cells is highly complex and direct experimental observations are challenging. We here develop a mathematical model which helps relate processes in the niche to measurable changes of stem and non-stem cell counts. HSC attached to the niche are assumed to be quiescent. After detachment HSC become activated and divide or differentiate. To maintain their stemness, the progeny originating from division must reattach to the niche. We use mouse data from literature to parametrize the model. By combining mathematical analysis and computer simulations, we systematically investigate the impact of stem cell proliferation, differentiation, niche attachment, and detachment on clinically relevant scenarios. These include bone marrow transplantation, clonal competition, and eradication of malignant cells. According to our model, sampling of blood or bulk marrow provides only limited information about cellular interactions in the niche and the clonal composition of the stem cell population. Furthermore, we investigate how interference with processes in the stem cell niche could help to increase the effect of low-dose chemotherapy or to improve the homing of genetically engineered cells.

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