Importance and regulation of adult stem cell migration

Abstract

Cell migration is an essential process throughout the life of vertebrates, beginning during embryonic development and continuing throughout adulthood. Stem cells have an inherent ability to migrate, that is as important as their capacity for self-renewal and differentiation, enabling them to maintain tissue homoeostasis and mediate repair and regeneration. Adult stem cells reside in specific tissue niches, where they remain in a quiescent state until called upon and activated by tissue environmental signals. Cell migration is a highly regulated process that involves the integration of intrinsic signals from the niche and extrinsic factors. Studies using three-dimensional in vitro models have revealed the astonishing plasticity of cells in terms of the migration modes employed in response to changes in the microenvironment. These same properties can, however, be subverted during the development of some pathologies such as cancer. In this review, we describe the response of adult stem cells to migratory stimuli and the mechanisms by which they sense and transduce intracellular signals involved in migratory processes. Understanding the molecular events underlying migration may help develop therapeutic strategies for regenerative medicine and to treat diseases with a cell migration component.

Keywords: cancer; cytoskeleton; migration; stem cells.

Figure 1

Stem cell migration is required for embryogenesis, for homeostasis and repair of adult tissues, but also plays an important role in the development of cancer. Therefore, migration capacity of stem cells is a fundamental characteristics necessary to carry out their function. The acquisition of knowledge of this process could be potentially used in cell therapy increasing and/or directing migration and in treatments of diseases with cell migration involved inhibiting this migration.

Figure 2

Stem cell behaviour is controlled by the niche which comprises their cellular, physical and chemical components. Cellular components include all the cells types that reside in the niche as blood vessels, immune cells or tissue‐specific cells. Secreted factors such as chemokines, growth factors or cytokines are considered chemical components of the niche. The physical components as extracellular matrix (ECM), mechanical forces are also involved in the regulation of stem cell functions. The quiescence, self‐renewal, proliferation, differentiation and migration of stem cells are governed by the combination of these three components of the niche.

Figure 3

Cells are able to sense a great variety of migratory stimuli using different types of receptors. They have receptors for soluble factors as chemokines and growth factor receptors. To sense environmental mechanical signals, cells have receptors as integrins and cadherins that have the capacity to translate mechanical signals into biochemical responses, knowing this process as mechanotransduction. Once the cell receives the signal (physical, chemical or cellular) different signalling pathways are triggered and converge on the Rho family of small GTPases which are considered as master regulators of actin cytoskeleton reorganization. They are molecular switches by cycling between a GTP‐bound active state (mediated by GEF) and a GDP‐bound inactive state (catalysed by GAP).