5.1 What is a Stem Cell?

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What is a Stem Cell?

 

Stem cells are classically defined as unspecialized cells with the ability to self-renew as well as clonally differentiate into specialized cell types [1, 2, 3]. Stem cells can be divided into pluripotent embryonic stem (ES) cells, which are capable of giving rise to all germline and somatic cell types, and adult stem cells, which can differentiate into at least one mature tissue-specific cell [1, 3, 4]. Stem cell fate, the choice between continued self-renewal or lineage commitment, is governed by intrinsic and extrinsic signals. Intrinsic signals include the expression of transcription factors necessary for maintenance and asymmetric division, while extrinsic signals include secreted factors and cell-to-cell interactions within a stem cell's niche/microenvironment [3].  As stem cells differentiate, they gradually lose their capacity for self-renewal and subsequently give rise to progenitor cells, which in turn develop into specialized cells along different lineages [6].

However, certain progenitor cells have been observed to revert into a more "stem-like" phenotype and renew their proliferative capacity [6, 7]. These observations differentiate the evolving view from the traditional view of stem cell development [6]. The traditional view proposes that stem cells undergo permanent differentiation into an absolute specialized cell.  On the other hand, the evolving view suggests that differentiation is not complete and that the cell retains some “stem-like” phenotype, allowing it to reverse its differentiation [6]. Although stem cells can be classified based on what cells types they give rise to and where they reside, we will only discuss them in in terms of being either embryonic or adult stem cells in this section. 

 

 

 

Embryonic Stem Cells

 

At the early stages of embryonic development, the inner cell mass of the blastocyst is made up of a few undifferentiated cells capable of forming all somatic and germline (i.e., ectoderm, mesoderm, endoderm) cells. These pluripotent cells are commonly known as embryonic stem (ES) cells [1, 4]. Due to their capacity for long term self-renewal and multi-lineage differentiation, ES cells possess enormous potential for applications in regenerative medicine and tissue engineering [1, 8].   

 

 

Adult Stem Cells

 

Adult stem cells are a rare population of non-embryonic stem cells which give rise to specialized cell types found within the same tissue of origin [1]. Like ES cells, adult stem cells have the capacity for self-renewal, though to a lesser extent [1, 8]. Due to the small population of adult stem cells, some progenitors with a limited self-renewal capacity act as transit amplifying cells (TACs) to help increase the production of specialized cells from adult stem cells [3]. Adult stem cells have been used successfully in the regeneration of damaged tissues resulting from injury or disease [1, 11, 12].

There are many different types of adult stem cells, some of which are summarized in Table 8.1.1.

 

Table 5.1.1. Characteristics of adult stem cell types.

Stem Cell Type

What they form?

Where they live?

Mesenchymal

Bone, cartilage, muscle, marrow stroma, CNS cells, skin, tendons, fat [10]

Marrow [10]

Neural

Neurons, astrocytes, oligodendrocytes

Cell centricular zone

Intestinal

Enterocytes, goblet cells, paneth cells, enteroendrocrine cells

Intestinal crypts

Muscle/Satellite

Muscle

Muscle fibers

Hematopoietic

All blood cells

Bone marrow

Endothelial

Endothelial cells lining inner surfaces of blood and lymphatic vesels

Bone marrow

Epidermal

Different layers of the epidermis

Basal layer of epidermis

Olfactory

All cells of olfactory epithelium

Lining of the nose

 

Adult stem cells may live in different structures as outlined above, but they all reside in defined anatomical niches, which are specific microenvironments restricting the differentiation of stem cells (11). Stem cell niches wil be further discussed in later sections of the chapter.

 

 

Cancer Stem Cells (CSCs)

 

Cancer stem cells (CSCs) represent a rare group of cells within a given tumor cell population that possesses the ability to self-renew and differentiate into diverse cell progenies. Much like the cancer phenotype itself, the CSC phenotype is thought to evolve by the acquisition of genetic and epigenetic alterations in normal stem cells, progenitor cells or differentiated cells. Stem cells may represent a critical component of the tumour cell population, and provide important targets for cancer therapies. 

 

The focus of this chapter is to elaborate upon the role of cancer stem cells as well as the use of stem cell isolation and research techniques. 

 

 

References

1. Commission on Life Sciences National Research Council. (2002). Stem cells and the future of regenerative medicine (Washington, D.C.: National Academy Press).

2. Weissman, I.L. (2000). Stem Cells: Units of Development, Units of Regeneration, and Units in Evolution. Cell 100, 157-168.

3. Watt, F.M., and Hogan, B.L.M. (2000). Out of Eden: Stem Cells and Their Niches. Science 287, 1427-1230.

4. Sylvester, K.G., and Longaker, M.T. (2004). Stem Cells Review and Update. Arch Surg 139, 93-99.

5. Blau, H.M., et al. (2001). The Evolving Concept of a Stem Cell: Entity or Function? Cell 105, 829-841.

6. van Es, J.H., et al. (2012). Dll1+ secretory progenitor cells revert to stem cells upon crypt damage. Nature Cell Biology 14, 1099-1104.

7. Eckfeldt, C.E., et al. (2005). The molecular repertoire of the 'almighty' stem cell. Nature Reviews Mol. Cell. Biol 6, 726-737.

8. Caplan, A.I. (2007) Adult Mesenchymal Stem Cells for Tissue Engineering Versus Regenerative Medicine. J. Cell. Physiol. 213, 341-347.

9. Bianco, P., and Robey, P.G. (2001).  Stem cells in tissue engineering. Nature 414, 118-121.

10. Pitterger, M.F., Mackay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., Moorman, M.A., Simonetti, D.W., Craig, S., Marshak, D.R. 1999. Multilineage potential of adule human mesenchymal stem cells. Science. 284(5411): 143-147

11. Scadden DT (2006). The stem-cell niche as an entity of action. Nature 441, 1075-1079.