Cardiac Cell Culture Technologies by Zbigniew Brzozka & Elzbieta Jastrzebska

Author:Zbigniew Brzozka & Elzbieta Jastrzebska
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

6.4 Mesenchymal Stem Cells—What Are They and Where Do They Come from?

Mesenchymal stem cells (MSCs) are heterogeneous population of postnatal cells that are present in adult organisms. The term “mesenchymal stem cells ” is pretty widely used to describe the populations of cells which differ in their localization and properties. Moreover, MSC term has also alternative meanings, such as multipotent stromal cells or mesenchymal stromal cells (Dominici et al. 2006). As a result, many controversies, for different reasons, arise around “MSCs.” First, MSCs are described as the multipotent, self-renewing “skeleton-related” stem cells , i.e., present within the mammalian bone marrow stroma. According to this concept, bone marrow stromal cells play a role in the growth and turnover of the bone, form hematopoietic microenvironment, and also are able to initiate and complete bone organogenesis in vivo (Bianco et al. 2013; Bianco 2014, 2015). Second, MSCs are often described as ubiquitous cells, present within the connective tissue of different organs, and able to adhere to the plastic during in vitro culture and also to differentiate into chondrocytes, adipocytes, and osteocytes (Dominici et al. 2006). Thus, each time one confronts the term MSCs, one has to ask the question about the characteristic of these cells.

The stringent and rigorous assays allowing to define stem cells base on the following clues: stemness probed during in vivo serial transplantations, self-renewal, i.e., ability to generate identical population of stem cells in vivo and clonogenity in vitro, i.e., ability to proliferate and give rise to cell colonies, long-term expansion in vitro without phenotypic change, and finally multipotency probed by in vivo differentiation assay (e.g., heterotopic transplantation) (Bianco et al. 2008, 2013). However, difficulties connected with in vitro culture and analysis of stem cells , in general, and mesenchymal stem cells , in particular, not always allow simple identification of a cell as a stem cell (Bianco et al. 2013).

The story of MSCs started in the 1960s when Friedenstein found skeletal stem/progenitor cells in the bone marrow stroma (Friedenstein et al. 1966). These bone marrow stromal cells (BMSCs) enclosed in a diffusion chamber and heterotopically transplanted subcutaneously produced bone and bone marrow (Friedenstein et al. 1987). The BMSCs grafted without chamber, i.e., in open transplants, formed bone that was colonized by host hematopoietic cells (Tavassoli and Crosby 1968). Thus, the naïve osteogenic potential of BMSCs and their ability to form hematopoietic microenvironment and hematopoietic stem cell (HSC) niche have been showed unquestionably (Friedenstein et al. 1968; Friedenstein and Kuralesova 1971). Further studies documented that the population of adherent BMSCs contains cells that are able to grow in vitro when cultured at clonal density and to form so-called colony-forming units-fibroblastic (CFU-F). These clonogenic cells, i.e., cells able to proliferate and give rise to cell colonies, were able to generate bone after their heterotopic transplantation in vivo (Friedenstein 1980; Friedenstein et al. 1987). Importantly, even single bone marrow-derived cell was able to give rise to bone, cartilage, and adipocytes, i.e., other types of connective tissue, after heterotopic transplantation (Friedenstein et al. 1987; Owen and Friedenstein 1988).

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