Stem cells obtained from early mammalian embryos and the subsequent establishment of self replicating embryonic stem cell lines (ES) provided a legacy resource of pluripotent cells capable of differentiating into specific cell lineages of the adult organism. Still the most versatile source of pluripotent cells, their application to potential human therapeutic use has been encumbered by various technical and ethical objections. New sources of embryonic pluripotent stem cells have been sought, the isolation of ES cell lines from a single blastomere that avoids destruction of the human embryo, the use of arrested embryos no longer capable of completing development or using post-implantation embryos as stem cell providers. The successful cloning and reprogramming of adult animal cell nuclei by somatic cell nuclear transplantation (SCNT) or nuclear transfer (NT) provides stem cells tailored to the donor organism, though a step away for human use. Variations in this procedure are altered SCNT, that would block human use for reproduction and the use of parthenotes to induce pluripotent stem cell lines. All of these NT methods depend upon a very limited supply of healthy oocyte host cells. Enucleated fertilized eggs have been substituted for oocytes and the production of stem cell somatic cell hybrids by cell fusion have potential use for nuclear transfer ES cells not directly dependent on oocytes. Recovery of cells from human amniotic fluid has yielded stem cells that share some pluripotent characteristics but are multipotent stem cells. Adult somatic cells have been reprogrammed recently by retroviral transduction using four transcription factors to induce pluripotent stem cells (iPS) with great promise. Each of these procedures has limitations at present for extensive use in human regenerative medicine.
The developmental potential of the limb regeneration blastema, a mass of mesenchymal cells of mixed origins, was once considered as being pluripotent, capable of forming all cell types. Now evidence asserts that the blastema is a heterogeneous mixture of progenitor cells derived from tissues of the amputation site, with limited developmental potential, plus various stem cells with multipotent abilities. Many specialized cells, bone, cartilage, muscle, and Schwann cells, at the injury site undergo dedifferentiation to a progenitor state and maintain their cell lineage as they redifferentiate in the regenerate. Muscle satellite reserve stem cells that are active in repair of injured muscle may also dedifferentiate and contribute new muscle cells to the limb blastema. Other cells from the dermis act as multipotent stem cells that replenish dermal fibroblasts and differentiate into cartilage. The blastema primordium is a self-organized, equipotential system, but at the cellular level can compensate for specific cell loss. It is able to induce dedifferentiation of introduced exogenous cells and such cells may be transformed into new cell types. Indigenous cells of the blastema associated with amputated tissues may also transform or possibly transdifferentiate into new cell types. The blastema is a microenvironment that enables dedifferentiation, redifferentiation, transdifferentiation, and stem cell activation, leading to progenitor cells of the limb regenerate.
Aside from the morphological similarities which they share with the chordates (Hyman, 1959), the Enteropneusta have developed regenerative methods common to both the invertebrates and the vertebrates. The regenerative capacity of the tongue worms has been noted in early reports by Spengel (1893) in Glossobalanus minutus, by Willey (1899) in Ptychodera flava, by Cori (1902) in Balanoglossus
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