Biomedical Engineering Reference
In-Depth Information
6.3.4 The Tissue Microenvironment: Cell Therapy and Bioreactor
Design Principles
A main task in tissue engineering is to recreate tissue function by constructing a tissue.
Achieving this goal is challenging, and it is based on some fundamental axioms:
The developmental program and the wound healing response require the systematic
and regulated unfolding of the information on the DNA through coordinated execution
of genetic subroutines and programs. Participating cells require detailed information
about the activities of their neighbors. Proper cellular communications are of key concern
and in many cases the concept of the “stem cell niche” is important.
Upon completion of organogenesis or wound healing, the function of fully formed
organs is strongly dependent on the coordinated function of multiple cell types. Tissues
function based on multicellular aggregates, called functional subunits of tissues.
The microenvironment has a major effect on the function of an individual cell. The
characteristic length scale of the microenvironment is 100
m.
The microenvironment is characterized by (1) neighboring cells: cell-cell contact, soluble
growth factors, and so on; (2) the chemical environment: the extracellular matrix, the
dynamics of the nutritional environment; and (3) the local geometry.
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Cellular Function In Vivo: The Tissue Microenvironment and Communication
An important requirement for successful tissue function is a physiologically acceptable
environment in which the cells will express the desired tissue function. One common
way to approach this goal is to attempt to recreate or mimic the physiological in vivo envi-
ronment. This task involves mimicking a variety of features of the microenvironment
including cell-cell and cell-matrix communications, the biochemical and mechanical milieu,
as well as communication between tissues.
Examples of tissue microenvironments are shown in Figure 6.25, and some are discussed
in Section 6.2.2. The communication of every cell with its immediate environment and other
tissues can be examined using a topological representation of the organization of the body.
The DNA in the center of the diagram contains the information that the tissue engineer
wishes to express and manage. This cell is in a microenvironment that has important
spatiotemporal characteristics.
Signals to the nucleus are delivered at the cell membrane and are transmitted through
the cytoplasm by a variety of signal transduction mechanisms. Some signals are delivered
by soluble growth factors after binding to the appropriate receptors. These growth factors
may originate from the circulating blood or from neighboring cells. Nutrients, metabolic
waste products, and respiratory gases traffic in and out of the microenvironment in a highly
dynamic manner. The microenvironment is also characterized by its cellular composition,
the ECM, and local geometry, and these components also provide the cell with important
signals. The size scale of the microenvironment is on the order of 100
m. Within this
domain, cells function in a coordinated manner. If this arrangement is disrupted, appropri-
ate cell function will not be obtained.
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