Stem Cell Defects Uncovered in DS

Down's syndrome (DS) is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21 and is the most common chromosome abnormality in humans, associated with physical growth delays and a severe degree of intellectual disability. It is also associated with early aging and related disorders and, as recent research has linked aging to impaired or exhausted stem cells (Liu and Rando), suggests that DS may also be associated with adult stem cell defects. In a recent report in ­Nature, researchers from the laboratory of Michael F. Clarke at Stanford University School of Medicine, California, USA have begun to unravel the molecular underpinnings of DS through the examination of one of the genes known to be triplicated in human DS: the deubiquitinase Usp16 gene. The group's exciting findings suggest that overexpression of Usp16 leads to dysfunction in multiple stem cells populations through epigenetic mechanisms which may give rise to the DS related phenotype (Adorno et al).

Immune Response to iPSC-Derivatives Analysed in Non-human Primates

Recent studies on the host immune response to induced pluripotent stem cells (iPSCs) in mice found that while iPSC-derived teratomas raised a potentially deleterious immune response in genetically identical mice (Zhao et al), their derivatives seem to lack this effect (Araki et al and Guha et al). To better simulate a clinical situation, in a recent study in Stem Cell Reports the group of Jun Takahashi at Kyoto University, Japan have compared immunological responses of dopaminergic (DA) neurons (the cells required for cell replacement therapy in Parkinson's Disease) derived from cynomolgus monkeys in an autologous and allogeneic manner (Morizane et al).

Cell Cycle and Stem Cells: An intimate Relationship Delineated

The importance of the cell cycle to human embryonic stem cells (hESCs) is demonstrated by a wealth of data emanating from multiple labs across the world. The unique pattern of the cell cycle in hESCs is signified by a large S phase and a short but vitally important G1 phase (Coronado et al and Savatier et al) which lengthens as a cell moves towards its final somatic state, indicating that differentiation affects cell-cycle regulation and that the short G1 phase is highly linked to the pluripotent state (Calder et al and Coronado et al). Moreover, research has also shown that pluripotent cells are more receptive to differentiation signals when in G1 compared to other phases of the cell cycle (Sela et al).   Siim Pauklin and Ludovic Vallier from the Cambridge Stem Cell Institute, University of Cambridge, UK have now utilised new tools in an attempt to delineate the mechanisms that integrate pluripotency, differentiation and the cell cycle in hESCs, in a study published in Cell with an excellent accompanying summary article.

Analyses of Immunosuppressants Effect on NSCs Therapeutic Function

Stem cell therapy in humans currently relies on the use of immunosuppressants to ensure long-term cell survival and function. Commonly used immunosuppressants include Cyclosporine A (CsA), tacrolimus (FK506) and sirolimus (rapamycin); all of which have been shown to have some effect on pathways present in neural cells (Aramburu et al and Hoeffer et al). Researchers from the groups of Aileen J. Anderson and Brian J. Cummings at the University of California, Irvine, California, USA have previously shown robust engraftment, survival, and differentiation of transplanted human central nervous system-derived neural stem cells propagated as neurospheres (hCNS-SCns) (Uchida et al) following SCI in mouse (Cummings et al and Salazar et al). Now, in a report in Stem Cells Translational Medicine, Sontag et al have investigated the potential effects of immunosuppressant treatment in this in vivo model system.

Age Related Decline in ASC Therapeutic Function in MS Model

Multiple sclerosis (MS) is a neurodegenerative disease characterized by inflammation and scarring throughout the central nervous system (CNS) which currently has no cure (Jadasz et al). Mesenchymal stem cell (MSC) transplantation is a potential therapy, due to their ability to migrate to areas of damage, release trophic factors and exert neuroprotective and immunomodulatory effects (Bai et al and Freedman et al). Clinical trials have also confirmed the safety of MSC therapy (Connick et al, and Uccelli et al). However, one question which remains unanswered is that of any correlation of MSC functionality with the age of the donor (Lassmann et al). Now, in a report in Stem Cells Translational Medicine, researchers from the laboratory of Bruce A. Bunnell at the Tulane University School of Medicine, New Orleans, Louisiana, USA have used an experimental mouse model of MS to analyse the functionality of MSCs derived from human adipose tissue (ASCs) from donors of different ages (Scruggs et al).