Adult Stem Cells

Adult stem cells are those cells found in tissues after birth that are able to self-renew and yield differentiated cell types. Initially it was thought that adult stem cells were only located in a limited selection of organs and could differentiate into just those phenotypes found in the originating tissue. The field is still developing, however, and recent studies have identified stem cells in more tissues and indicate a greater range of potential than that originally believed. Already stem cells have been derived from human bone marrow (Edwards, 2004), blood (Ogawa, 1993; Asahara et al., 1997), brain (Steindler and Pincus, 2002), fat (Zuk et al., 2002), liver (Tosh and Strain, 2005), muscle (Alessandri et al., 2004), pancreas (Zulewski et al., 2001), and umbilical cord blood (Erices et al., 2000; Benito et al., 2004).

As with many rapidly expanding fields, the use of non-standardized methods makes interpreting results from different investigators difficult, and this thus has led to controversy. Since adult stem cells are often a very small percentage of the total cells isolated from a given tissue, generating a pure population is difficult. In many cases different investigators use different means of isolating the stem cells from a given tissue. The question then arises whether the stem cells generated from the various techniques are identical or distinct stem cell populations. This difficulty is further exacerbated as these cells are commonly identified using a range of criteria, such as isolation procedure, morphology, protein expression, etc., leaving some question as to the defining characteristics of these stem cell populations.

The potential to yield mature phenotypes is typically shown through either differentiation in vitro using biochemical cues or implantation in vivo in immunosuppressed mice. The lack of lineage tracing and clonal expansion in some studies has called into question whether observed phenotypes are due to the differentiation potential of a stem cell or to a heterogeneous initial population. As standardized protocols develop for adult stem cells, more rigorous criteria will develop for determining stem cell populations and their differentiation potential.

There is a growing argument that all adult stem cells may have a signature expression profile. It is possible that self-renewing capabilities combined with multipotency, regardless of the cell origin, are associated with a set of characteristic properties. While such properties have not yet been determined, one candidate may be dye exclusion. When stained with Hoechst, some adult stem cells have been found to actively exclude the dye using transmembrane pumps. These cells have been coined side population cells, as they appear in a peripheral area when analyzed by flow cytometry using a UV laser. Originally identified in murine bone marrow (Goodell et al., 1996), the commonality of this functional property across adult stem cells has best been shown in the mouse model, where side population cells have been found in muscle, liver, lung, brain, kidney, heart, intestine, mammary tissue, and spleen (Asakura and Rudnicki, 2002). Expression of the ABCG2 protein, which plays a role in the transmembrane pump (Scharenberg et al., 2002), may be a convenient expression marker of this functional property. It is still unclear, however, which signature expressions, if any, are inherently associated with all adult stem cells.

While adult stem cells may ultimately be derived from practically every tissue in the body, there is a subset, based on ease of isolation, availability, or potency, that is most likely to contribute to regenerative medicine. These stem cells, and the phenotypic lineages they have been shown to generate, are indicated in Table 3.2. Bone marrow- and blood-derived stem cells are fairly easy to isolate and have been the most thoroughly investigated. Both contain hematopoietic stem cells (HSCs) (Ogawa, 1993; Tao and Ma, 2003), which give rise to blood cells, and endothelial progenitor cells (EPCs) (Asahara et al., 1997; Kocher et al., 2001). Bone marrow additionally contains mesenchymal stem cells (MSCs) (Pittenger et al., 1999; Jiang et al., 2002), which have been shown to differentiate into mesodermal phenotypes, including orthopedic and vascular. The low yield of stem cells from marrow and blood motivates efforts to find alternative adult stem cell sources. HSCs and MSCs can also be derived from umbilical cord blood (Broxmeyer et al., 1989; Erices et al., 2000). As a widely available source of stem cells with extensive expansion capabilities in vitro, stored umbilical cord blood is considered an exciting resource for regenerative medicine applications (Chiu et al., 2005). One plentiful autologous adult stem cell source is fat. Lipoaspirate-derived stem cells have yet to be thoroughly investigated, but have already been shown to differentiate into multiple phenotypes (Zuk et al., 2002; Ashjian et al., 2003; Huang, J.I., et al., 2004). Overall, the proven differentiation potential of human adult stem cells is limited. Research in stem cell plasticity and animal adult stem cells, however, implies that the full potential of human adult stem cells is likely to be more extensive than has been currently shown.

Table 3.2. Differentiated cells derived from human adult stem cells

PLA: processed lipoaspirate

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Adult Stem Cell - an overview | ScienceDirect Topics