New Paths to Pluripotent Stem Cells

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.