Chapter 066. Stem Cell Biology (Part 2)

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Self-Renewal and Proliferation of Stem Cells Symmetric and Asymmetric Cell Division The most widely accepted stem cell definition is a cell with a unique capacity to produce unaltered daughter cells (self-renewal) and to generate specialized cell types (potency). Self-renewal can be achieved in two ways. Asymmetric cell division produces one daughter cell that is identical to the parental cell and one daughter cell that is different from the parental cell and is a progenitor or differentiated cell. Asymmetric cell division does not increase the number of stem cells. Symmetric cell division produces two identical daughter cells. For stem cells to proliferate...

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Chapter 066. Stem Cell Biology (Part 2) Self-Renewal and Proliferation of Stem Cells Symmetric and Asymmetric Cell Division The most widely accepted stem cell definition is a cell with a unique capacity to produce unaltered daughter cells (self-renewal) and to generate specialized cell types (potency). Self-renewal can be achieved in two ways. Asymmetric cell division produces one daughter cell that is identical to the parental cell and one daughter cell that is different from the parental cell and is a progenitor or differentiated cell. Asymmetric cell division does not increase the number of stem cells. Symmetric cell division produces two identical daughter cells. For stem cells to proliferate in vitro, they must divide symmetrically. Self-renewal alone cannot define stem cells, because any established cell line, e.g., HeLa cells or NIH3T3 cells, proliferate by symmetric cell division.
Unlimited Expansion In Vitro Resident stem cells are often quiescent and divide infrequently. However, once the stem cells are successfully cultured in vitro, they often acquire the capacity to divide continuously and the ability to proliferate beyond the normal limit of passages typical of primary cultured cells (sometimes called immortality). These features are primarily seen in ES cells, but have also been demonstrated for NS cells, MS cells, MAPCs, maGSCs (adult-derived tissue stem cells), and USSCs (newborn-derived tissue stem cells), thereby enhancing the potential of these cells for therapeutic use (Table 66-1). Stability of Genotype and Phenotype The capacity to actively proliferate is associated with the potential accumulation of chromosomal abnormalities and mutations. Mouse ES cells have been extensively used to produce gene-targeted animals and are known to maintain their euploid karyotype and genome integrity. In contrast, human ES cells appear to be more susceptible to mutations after long-term culture. Another limitation is the possible formation of tumors after transplanting actively dividing stem cells. Mouse ES cells can form teratomas when injected into immunosuppressed animals. Potency and Differentiation of Stem Cells
Developmental Potency The term potency is used to indicate a cell's ability to differentiate into specialized cell types. The current lack of knowledge about the molecular nature of potency requires the experimental manipulation of stem cells to demonstrate their potency. For example, in vivo testing can be done by injecting stem cells into mouse blastocysts or immunosuppressed adult mice and determining how many different cell types are formed from the injected cells. In vitro testing can be done by differentiating cells in various culture conditions to determine how many different cell types are formed from the cells. The in vivo assays are not applicable to human stem cells. The formal demonstration of self-renewal and potency is performed by demonstrating that a single cell possesses such abilities in vitro (clonality). Cultured stem cells are tentatively grouped according to their potency (Fig. 66-1). Figure 66-1
Potency and source developmental stage of cultured stem cells. For abbreviations of stem cells, see Table 66-1. Note that stem cells are often abbreviated with or without "cells," e.g., ES cells or ESCs for embryonic stem cells. m, mouse; h, human From Totipotency to Unipotency Totipotent cells can form an entire organism autonomously. Only a fertilized egg (zygote) possesses this feature. Pluripotent cells (e.g., ES cells) can form almost all the body's cell lineages (endoderm, mesoderm, and ectoderm), including germ cells. Multipotent cells (e.g., HS cells) can form multiple cell lineages but cannot form all of the body's cell lineages. Oligopotent cells (e.g., NS cells) can form more than one cell lineage but are more restricted than multipotent cells. Oligopotent cells are sometimes called progenitor cells or precursor cells; however, these terms are often more strictly used to define partially differentiated or lineage-committed cells (e.g., myeloid progenitor cells) that can divide into different cell types but lack self-renewing capacity. Unipotent cells or monopotent cells, e.g., spermatogonial stem (SS) cells, can form a single differentiated cell lineage. Terminally differentiated cells, such as fibroblast cells, also have a capacity to proliferate (which may be called self-renewal) but maintain the same cell type (e.g., no potency to form another cell type) and are not, therefore, considered unipotent cells.