Chapter 066. Stem Cell Biology (Part 2)

Self-Renewal and Proliferation of Stem CellsSymmetric and Asymmetric Cell DivisionThe 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) 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 uniquecapacity to produce unaltered daughter cells (self-renewal) and to generatespecialized cell types (potency). Self-renewal can be achieved in two ways.Asymmetric cell division produces one daughter cell that is identical to the parentalcell and one daughter cell that is different from the parental cell and is a progenitoror differentiated cell. Asymmetric cell division does not increase the number ofstem cells. Symmetric cell division produces two identical daughter cells. For stemcells to proliferate in vitro, they must divide symmetrically. Self-renewal alonecannot define stem cells, because any established cell line, e.g., HeLa cells orNIH3T3 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 thecapacity to divide continuously and the ability to proliferate beyond the normallimit of passages typical of primary cultured cells (sometimes called immortality).These features are primarily seen in ES cells, but have also been demonstrated forNS cells, MS cells, MAPCs, maGSCs (adult-derived tissue stem cells), andUSSCs (newborn-derived tissue stem cells), thereby enhancing the potential ofthese cells for therapeutic use (Table 66-1). Stability of Genotype and Phenotype The capacity to actively proliferate is associated with the potentialaccumulation of chromosomal abnormalities and mutations. Mouse ES cells havebeen extensively used to produce gene-targeted animals and are known tomaintain their euploid karyotype and genome integrity. In contrast, human EScells appear to be more susceptible to mutations after long-term culture. Anotherlimitation is the possible formation of tumors after transplanting actively dividingstem cells. Mouse ES cells can form teratomas when injected intoimmunosuppressed animals. Potency and Differentiation of Stem Cells Developmental Potency The term potency is used to indicate a cells ability to differentiate intospecialized cell types. The current lack of knowledge about the molecular natureof potency requires the experimental manipulation of stem cells to demonstratetheir potency. For example, in vivo testing can be done by injecting stem cells intomouse blastocysts or immunosuppressed adult mice and determining how manydifferent cell types are formed from the injected cells. In vitro testing can be doneby differentiating cells in various culture conditions to determine how manydifferent cell types are formed from the cells. The in vivo assays are not applicableto human stem cells. The formal demonstration of self-renewal and potency isperformed 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. Forabbreviations of stem cells, see Table 66-1. Note that stem cells are oftenabbreviated with or without cells, e.g., ES cells or ESCs for embryonic stemcells. m, mouse; h, human From Totipotency to Unipotency Totipotent cells can form an entire organism autonomously. Only afertilized egg (zygote) possesses this feature. Pluripotent cells (e.g., ES cells) canform almost all the bodys cell lineages (endoderm, mesoderm, and ectoderm),including germ cells. Multipotent cells (e.g., HS cells) can form multiple celllineages but cannot form all of the bodys cell lineages. Oligopotent cells (e.g., NScells) can form more than one cell lineage but are more restricted than multipotentcells. Oligopotent cells are sometimes called progenitor cells or precursor cells;however, these terms are often more strictly used to define partially differentiatedor lineage-committed cells (e.g., myeloid progenitor cells) that can divide intodifferent cell types but lack self-renewing capacity. Unipotent cells or monopotentcells, e.g., spermatogonial stem (SS) cells, can form a single differentiated celllineage. Terminally differentiated cells, such as fibroblast cells, also have acapacity to proliferate (which may be called self-renewal) but maintain the samecell type (e.g., no potency to form another cell type) and are not, therefore,considered unipotent cells.