Hematopoietic tissue engineering: Effects of fluid dynamics and mass transfer on cell growth and migration.
Peng, Ching-An
1995
Abstract
Tissue function is a complex interplay between biological and physicochemical rate processes. The design of bioreactors must account for these processes simultaneously in order to obtain a bioreactor that provides a uniform environment for tissue growth and development. To date, the techniques for the growth of hematopoietic (blood-forming) cells on stromal (feeder) layers in long-term ex vivo bone marrow cell culture have been established. However, the processes involved in the development of bone marrow in extracorporeal devices are not well characterized. In this study, engineering analyses are applied to investigate the interaction of biological and physicochemical processes within bone marrow bioreactors which are of a parallel-plate configuration. In the bioreactor, the hematopoietic cells grow on a stromal layer that secretes cytokines that stimulate hematopoietic stem cell replication, differentiation and migration. The biological dynamics are described by a uni-lineage model that describes the replication and differentiation of the tissue stem cell. The physicochemical rates are described by the Navier-Stokes and convection-diffusion equations. A cell-chemotactic transport model is then proposed to describe cell migration. These model equations are solved by the finite element method and Runge-Kutta method. Two dimensionless groups govern the uniformity of cell growth. One is the Graetz number (Gz) that describes the relative rates of convection and diffusion, and the other is a new dimensionless ratio that describes the interplay of the growth factor production, diffusion and stimulation. The simulation results of cell-chemotactic model indicate that the spatio-temporal distribution of cells is governed by the interaction of cell chemotactic migration and cell mitosis. A dimensionless number that balances these two effects predicts the extent of non-uniformity in slab chambers. Based on the measured ex vivo oxygen uptake rate of bone marrow cells, a mathematical model of oxygen diffusion is formulated and used to investigate issues associated with hematopoietic bioreactor design including initial cell density, medium depth, and oxygen tension. High density hematopoietic cultures present design challenges in terms of sufficient and uniform delivery of oxygen to an active hematopoietic culture. These challenges can be met by using parallel plate bioreactors with thin liquid layers. Among the parallel-plate configurations analyzed, the radial-flow type bioreactor provides the most uniform environment in which hematopoietic cells can grow and differentiate ex vivo due to the absence of walls that are parallel to the flow paths creating slow flowing regions.Subjects
Cell Migration Dynamics Effects Engineering Fluid Growth Hematopoietic Mass Tissue Transfer
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