Designing and Engineering Stem Cell Niches

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Engineering Stem Cell Niches Ana I. Teixeira, Ola Hermanson, and Carsten Werner

Abstract Stem cells have received a lot of attention due to great promises in medical treatment, for example, by replacing lost and sick cells and re-constituting cell populations. There are several classes of stem cells, including embryonic, fetal, and adult tissue specific. More recently, the generation of so-called induced pluripotent stem (iPS) cells from differentiated cells has been established. Common criteria for all types of stem cells include their ability to self-renew and to retain their ability to differentiate in response to specific cues. These characteristics, as well as the instructive steering of the cells into differentiation, are largely dependent on the microenvironment surrounding the cells. Such “stem cell friendly” microenvironments, provided by structural and biochemical components, are often referred to as niches. Biomaterials offer attractive solutions to engineer functional stem cell niches and to steer stem cell state and fate in vitro as well as in vivo. Among materials used so far, promising results have been achieved with low-toxicity and biodegradable polymers, such as polyglycolic acid and related materials, as well as other polymers used as structural “scaffolds” for engineering of extracellular matrix components. To improve the efficiency of stem cell control and the design of the biomaterials, interfaces among stem cell research, developmental biology, regenerative medicine, chemical engineering, and materials research are rapidly developing. Here we provide an introduction to stem cell biology and principles of niche engineering and give an overview of recent advancements in stem cell niche engineering from two stem cell systems—blood and brain.

Introduction Stem cells show great promise for use in medical treatment (e.g., by cell therapy [transplantation]) when sick cells are to be replaced by healthy ones. An alternative approach could be to activate dormant endogenous stem cell populations. Stem cells also may be used as vehicles for drug delivery. In addition, by studying stem cells and the mechanisms that control stem cell characteristics, we learn more about other types of disease, such as developmental and genetic defects, and cancer. While aiming at engineering stem cell–promoting microenvironments, we learn more about biomaterials, bioengineering, and protein characteristics. However, there is still a long way to go for stem cell therapy to become a reality in many medical disciplines, and an increased understanding of the signals

and cues that maintain and steer stem cell state and fate is highly desired. Two features common for all stem cells are the abilities to (1) self-renew and (2) to differentiate and mature into at least one terminal cell type.1 Self-renewal is defined as giving rise to at least one identical cell after cell division. This is regarded as a required signature for a stem cell; however, note that the issue of true selfrenewal is highly discussed in the field.2 Stem