Stem cell therapeutics—reality versus hype and hope

Abstract

In the last decade medical science has started to make the first steps towards a paradigm shift from repair to regeneration [1]. The potential use of a range of stem cells in regenerative medicine is currently one of the most intensively researched areas worldwide [2]. In particular, embryonic stem cells (ESC) and more recently Induced Pluripotent Stemcells (iPS) [3] have provoked a lot of interest as a potential source of stem cells in the treatment of diseases such as Alzheimer’s and Parkinson’s diseases. Nevertheless, these hopes have not yet been fulfilled with either ESC or iPS. Murine ESC were first described in 1981 [4] and subsequent studies showed the regenerative potential of murine stem cells derived from both preand postimplantation embryos [5–7]. This early murine work was followed by the development of human ESC in 1998 [8]. Both murine and human pre-implantation ESC are derived from the inner cell mass (ICM) of the blastocyst at day 5/6 of growth. The ICM consists of primitive ectoderm cells, which subsequently develop into epiblast cells in postimplantation embryos. Despite these ontogenic similarities human and murine ESC do not resemble each other in many aspects [9]. For example, murine ESC rely on leukemia inhibitory factor (LIF) and bone morphogenic protein-4 (BMP4) for maintenance of pluripotency [10, 11], whilst human ESC are dependent on TGFβ/Activin/Nodal pathway activity and fibroblast growth factor-2 (FGF2) [12–17] and thus resemble epiblast stem cells (EpiSC). Usually EpiSC cannot be reverted to a state such that they respond to LIF and BMP4. Furthermore, primordial germ cells, which originate from pluripotent epiblast cells in mice, respond in a similar way to LIF and BMP4, such as murine ESC derived from the ICM [18]. Additionally, murine ESC can be cultured as single cells while human ESC are particularly sensitive to dissociation and should be cultured in clumps [19]. There are clearly many basic concepts still to be explored in the biology of ESC of various species. Thorough understanding of these cells is still in its’ infancy despite 20 years of basic research. Bearing this is mind there should be an air of caution when proposing future clinical applications. Can or should we move forward into thinking about clinical applications when the fundamentals Capsule Human cord blood stem cells have a realistic and proven potential for the treatment of various diseases compared to embryonic stem cells / iPS cells.