A multiscale model of the bone marrow and hematopoiesis

Ariosto Silva; Alexander R. A. Anderson; Robert Gatenby

doi:10.3934/mbe.2011.8.643

Article Contents

2011, Volume 8, Issue 2: 643-658. Doi: 10.3934/mbe.2011.8.643

This issue Previous Article A delay-differential equation model of HIV related cancer--immune system dynamics Next Article

A multiscale model of the bone marrow and hematopoiesis

1.
H Lee Moffitt Cancer Center, 12902 Magnolia Dr, Tampa, FL 33612
2.
H. Lee Moffitt Cancer Center & Research Institute, Integrated Mathematical Oncology, 12902 Magnolia Drive, Tampa, FL 33612

Received: February 28, 2010

Revised: November 30, 2010

Published: March 2011

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Abstract

The bone marrow is necessary for renewal of all hematopoietic cells and critical for maintenance of a wide range of physiologic functions. Multiple human diseases result from bone marrow dysfunction. It is also the site in which liquid tumors, including leukemia and multiple myeloma, develop as well as a frequent site of metastases. Understanding the complex cellular and microenvironmental interactions that govern normal bone marrow function as well as diseases and cancers of the bone marrow would be a valuable medical advance. Our goal is the development of a spatially-explicit in silico model of the bone marrow to understand both its normal function and the evolutionary dynamics that govern the emergence of bone marrow malignancy. Here we introduce a multiscale computational model of the bone marrow that incorporates three distinct spatial scales, cell, hematopoietic subunit, whole marrow. Our results, using parameter estimates from literature, recapitulates normal bone marrow function and suggest an explanation for the fractal-like structure of trabeculae and sinuses in the marrow, which would be an optimization of the hematopoietic function in order to maximize the number of mature blood cells produced daily within the volumetric restrictions of the marrow.

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Mathematics Subject Classification: Primary: 92B05; Secondary: 92C99.

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