All the adult stem cells, where do they all come from? An external source for organ-specific stem cell pools

Stem cells can self-renew and maintain the ability to differentiate into mature lineages. Whereas the "stemness" of embryonic stem cells is not discussed, the primitiveness of a stem cell type within adult organisms is not well determined. Data presently available are either inconclusive or controversial regarding two main topics: maintenance or senescente of the adult stem cell pool; and pluripotentiality of the cells. While programmed senescence or apoptosis following uncorrected mutations represent no problem for mature cells, the maintenance of the stem cell pool itself must be assured. Two different mechanisms can be envisaged for that. In the first mechanism, which is generally accepted, stem cells originate during ontogeny along with the organ which they are responsible for, and remain there during all the lifespan of the organism. Several observations derived from recent reports allow the suggestion of a second mechanism. These observations include: organ-specific stem cells are senescent; adult stem cells circulate in the organism; stem cell niches are essential for the existence and function of stem cells; adult stem cells can present lineage markers; embryo-like, pluripotent stem cells are present in adult organisms, as shown by the development of teratomas, tumors composed of derivatives of the three germ layers; and the fact that the gonads may be a reservoir of embryo-like, pluripotent stem cells in adult organisms. The second mechanism for the maintenance of adult stem cells compartments implies a source external to the organ they belong, consisting of pluripotent, embryo-tike cells of unrestricted life span, presenting efficient mechanisms for avoiding or correcting mutations and capable to circulate in the organism. According to this model, primitive stem cells exist in a specific organ in adult organisms. They undergo asymmetrical divisions, which originate one "true" stem cell and another one which enters the pool of adult stem cells, circulating through the entire organism. Upon signals liberated by organ-specific niches, this cell becomes activated to express lineage-specific genes, homes to that particular organ and repopulates its stem cell compartment, differentiating thus in what is seen as the organ-specific stem cell. The gonads are the natural candidates for homing the primitive stem cells in adult organisms. The model proposed Hin this work for the maintenance of organ-specific stem cell pools from an external source, represented by primitive, embryo-like germinal stem cells present in testes and ovaries, may contribute to the more complete understanding of this complex issue. (c) 2004 Elsevier Ltd. All rights reserved.