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CHA PTE R

Computational Simulation of Cell Behavior

for Tissue Regeneration

S.Jamaleddin Mousavi* ,†,‡ , Mohamed H. Doweidar* ,†,‡

*Mechanical Engineering Department, School of Engineering and Architecture (EINA), University of Zaragoza,
†
‡
Zaragoza, Spain Arago ´n Institute of Engineering Research (I3A), University of Zaragoza, Zaragoza, Spain Biomedical
Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain

15.1 INTRODUCTION

In this chapter, a numerical discrete model is represented to consider the role of cell migration in different processes
such as cell differentiation, cell proliferation, and cell morphology. Cell migration is essential for normal tissue devel-
opment and morphogenesis of the human body and organ systems. Therefore, over the last few decades, the inves-
tigation of cell behavior in the presence of different stimulating cues has become a hotbed for researchers. It is well
known that cell migration regulates numerous physiological processes, such as morphogenesis [1–6], tissue develop-
ment [7, 8], cell differentiation and proliferation [9–11], and pathological processes such as wound healing [12, 13] and
tumor metastasis [14, 15].
In the case of tissue development, the tissue should be generated in a correct geometry with a proper cell type.
Abnormal cell migration may lead to uncontrolled states such as invasion and the metastasis of cancer. In such cases,
cells may migrate in individual routines or in groups of cells as tightly associated epithelial sheets or clusters (e.g.,
Drosophila border cells and zebrafish lateral line primordium), or they may possess a mesenchymal character such
as during gastrulation and neural crest migration [1]. Wound healing is another coordinated multicell response pro-
grammed through a defined timetable in which each phase prepares the wound for subsequent phases that are
required for reestablishing the tissue. One of the most important stages in this timetable is cell migration, by which
fibroblasts migrate in the direction of the wound to improve the matrix structure and to modify the wound contraction
[16]. Stimuli that regulate cell behavior may change the rate of cell migration toward the wound to speed up wound
healing [17]. Additionally, a change of cell morphology is another significant parameter in wound healing during
which cells lengthen themselves during their migration toward wound locations [12] to cover the wound through
changing their shape to fill all intercellular gaps [13]. Further, malignant cells invade healthy tissues during metastasis
in response to different conditions. For instance, neoplastic cells follow this process to come into lymphatic and blood
vessels to spread into the circulatory system, causing metastatic development in distant organs [18].
Stem cells have the potential to proliferate or differentiate into different cell phenotypes. Different signaling such as
physicochemical factors, including particular mechanical mechanisms, can control both processes. However, the
control of stem cell lineage specification by mechanical cues is less understood. However, certain key themes have
been experimentally proven. For instance, stem cells can experience any alterations in the stiffness of their surrounding
microenvironment and consequently differentiate to a specific lineage specification. Besides, external mechanical
forces exerted on the stem cells can control stem cell differentiation to a specific cell phenotype. In addition, the
differentiation process can affect the mechanical properties of the cells and their specific subcellular components.
The combination of these three fundamental concepts allows introducing a new theory for the behavior of stem
cells [19, 20].

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