Концепция ниши стволовых клеток | ПРЕЦИЗИОННАЯ ОНКОЛОГИЯ

Концепция ниши стволовых клеток

Principles of stem cell biology and cancer: future applications and therapeutics. Edited by T. Regad, T. J. Sayers and R. C. Rees. John Wiley & Sons (2015)

Part I. Stem Cells


В нормальных взрослых тканях стволовые клетки отвечают за обновление, репарацию, и ремоделирование за счет своей способности к самообнавлению и мультипотентности. Они поддерживают гомеостаз тканей при различных физиологических (старение) и патологических (повреждение или заболевание) состояниях в течение всей продолжительности жизни организма. Такой гомеостаз зависит от способности стволовых клеток поддерживать себя длительное время (самообнавление) и дифференцироваться во множественные, но ограниченные, клеточные типы (мультипотентность). Регулируя деления клеток для удовлетворения потребности резидентских тканей, стволовые клетки делают возможной пожизненную оптимизацию тканей и формирование и функционирование органов (О’Брайен и Bilder, 2013). Баланс между самообнавлением и дифференцированием — основа поддержания и восстановления гомеостаза тканей. Гомеостаз может достигаться комбинированным действием различных внеклеточных компонентов как регуляторов этих двух отличительных процессов. Внеклеточные компоненты преимущественно состоят из внеклеточного матрикса (ECM) , который задействуется в клеточной адгезии, межклеточной коммуникации и дифференцировании, клеток и факторов роста (Abedin и King, 2010; Brizzi с соавт., 2012).

In 1977, it was demonstrated that many different cells, including endothelial cells and macrophages, could interact with haematopoietic stem cells (HSCs), to support their survival and differentiation (Dexter et al., 1977). Other studies have shown that many other cells are able to function as a supportive stroma (stromal cells) for HSCs, including adventitial reticular cells (Weiss, 1976), osteoblasts (Calvi et al., 2003), glial cells (Yamazaki et al., 2011), adipocytes (Naveiras et al., 2009), fibroblasts and mesenchymal stem cells (MSCs) (Bianco, 2011). These cells are able to produce a broad combination of ECM and growth factors and to express cell membrane molecules that can interact with and control the self-renewal and differentiation of HSCs (Kunisaki et al., 2013; Morrison and Scadden, 2014). The association of ECM, cells and growth factors organizes the bone microenvironment, which ultimately regulates HSCs. Although complex, the microenvironment influences haematopoiesis in a coordinated manner to maintain homeostasis of the organism. The ability of HSCs to sense and respond to organismal needs derives, in large part, from their intimate association with this microenvironment.

Schofield (1978) proposed the existence of a niche for HSCs that could dynamically regulate stem cell behaviour, maintaining equilibrium amongst quiescence, self-renewal and differentiation. The stem cell niche was understood as a physiological microenvironment consisting of specialized cells within fixed compartments that would act as stromal cells to HSCs and provide the growth factors and ECM required to maintain HSC properties. This niche can be viewed as specific areas of a tissue with local and specialized microenvironments consisting of soluble and surface-bound signalling factors, cell – cell contacts, stem-cell-niche support cells and the ECM, all able to maintain stem cell functions (Figure 3.1). In sum, the stem cell niche provides a protective environment that regulates proliferation, differentiation and apoptosis to control stem cell reserves. Thus, maintaining a balance between stem cell quiescence and activity is a hallmark of a functional niche (Moore and Lemischka, 2006).

Although the idea of a stem cell niche originates from studies on mammalian HSCs, a detailed description of a stem cell compartment at the cellular level was first achieved in the Drosophila melanogaster ovary (Xie and Spradling, 2000; Losick et al., 2011). Since then, the concept of the stem cell niche has been extended to include various stem cell types, including the progenitors of mammalian gut and hair cells.

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