In the January 6th issue of Cell Stem Cell, E. Salero et al. from the Neural Stem Cell Institute (Rensselar, NY) published their study results on isolating adult human stem cells from the retinal pigment epithelium (RPE). This subpopulation of cells from adult human RPE were activated in vitro and found to have self-renewing properties and the potential to differentiate into cells representing all three germ layers as well progenies of mesenchymal stem cells (MSCs). Clonal analyses demonstrated that the RPE-derived stem cells (RPESCs) are multipotent and they were able to differentiate into stable RPE cells. The investigators also reported that they were able isolate RPESCs from the elderly including a 99 years old donors. The authors concluded from their experimental observations that establish "RPESC as an accessible, human CNS-derived multipotent stem, useful for the stuyd of fate choice, replacement therapy, and disease modeling."

In the January 6th online edition of Stem Cells, M. H. Kamal et al. from MD Anderson Cancer Center (Houston, TX) published their experimental results on the regulation of gliboblastoma-derived stem-like cells (GSCs) and their ability to self renew. With cells from glioblastoma multiforme(GBM) tumors, the investigators found that different patients' specimens had varying expression levels in the transcriptional repressor, REST. Additionally, the experimental data revealed that REST maintained self-renewal in GSCs in which its high level of expression produced tumors that were morphologically distinct from tumors derived GSCs expressing low levels of REST. Knockdown of REST in GSCs with high REST resulted in GSCs producing tumors with low invasive properties and highly apoptotic when transplanted into mice. Conversely, forced expression of exogenous REST in GSCs producing low REST produced tumors that were highly invasive and decreased survival in transplanted mice. Based upon their results, the authors proposed "that a novel function of REST is to maintain self-renewal and other oncogenic properties of GSCs and that REST can play a major role in mediating tumorigenicity in GBM."

In the December 29th online edition of Stem Cells, R. Zhang et al. from Sichuan University (China) reported their study results on the mechanisms driving differentiation both in vivo and in vitro for human adipose-derived stem cells (hASCs). The investigators conducted excperiments in which they examined smooth muscle differentiation when the hASC were injected into smooth muscle of the urinary bladder as well co-cultures of the hASCs with primary smooth muscle cells in vitro. The experimental data revealed a time dependent differentiation of hASC into smooth muscle resulting from cues of the microenvironment. Chromosomal analysis demonstrated that nuclear fusion was not involved. The authors concluded from their observation "that cell plasticity is present in hASCs and their differentiation is accomplished in the absence of nuclear fusion."

In the December 27th online edition of PNAS, R. M. Kanashiro-Takeuchi et al. from the University of Miami published their study results the effects of the growth hormone releasing hormone (GHRH) on recovery of ventricular function following myocardial infarction (MI). The investigators performed animal experiments based upon the observation that a GHRH agonist reversed ventricular remodeling and enhanced functional recovery in chronic MI models. One month post MI, the animals received either placebo, GHRH agonist, rat recombinant GH, GHRH antagonist, GHRH agonist (GHRH-A), or a combination of the GHRH agonist plus antagonist. Following morphometric, immunoflourescence and quanatative RT-PCR analyses, the experiment data revealed that GHRH-A markedly improved cardiac function, MI size substantially reduced, and an increase in both myocyte and nonmyocyte mitoses. GHRH-A was also found to increase ex vivo expansion of cardiac stem cells which was "offset" by the introduction of a GHRH antagonist. The authors concluded from their observations thaat GHRH signaling is an important pathway within the heart that can substantially improve cardiac performance and reduce infarct size, "suggesting a regenerative process."

In the December 16th online edition of PNAS, N. Quarto et al. from Stanford University of School of Medicine published their study observations on comparing the phenotypes of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) carrying the mutant gene found in Marfan syndrome (MFS). MFS is characterized by mutations in the gene encoding for FIBRILLIN-1 (FBN1) which results in abnormal ocular, skeletal, and cardiovascular development. Mutation in FBN1 results in upregulation in TGF-β signaling which inhibits osteogenesis in ESCs. The investigators also found that the skeletal phenotypes observed in human ESCs carrying the FBN1 mutation are faithfully copied in iPSCs derived from MFS patient fibroblasts. Since the experimental results "demonstrate the faithful alignment of phenotypes in differentiated cells obtained from both ESCs and iPSCs" from MFS patients, the authors concluded from their observation that both human ESCs and iPSCs can provide complementary tools for uncovering the molecular pathogenesis in MFS.

In the December 12th online edition of PNAS, M. Agostini et al. from Leicester University (U.K.) reported their study results on the uncovering the role of p73 and miR-34a axis in modulating neuronal development. The investigators found that p73 drives the expression of miR-34a in mouse cortical neurons. It also discovered from the experimental results, that miR-34a in turn modulates the synaptotagmin-1 and syntaxin-1A. Expression of this axis is retained in embryonic stem cells that are differentiating into a neurological phenotype. However, overexpression of miR-34a results in electrophysiologic changes such as a reduction in spinal function. The authors concluded from their study's observation that " the TAp73/miR-34a axis has functional relevance in primary neurons...as well as reinforcing "a role for miR-34a in neuronal development."

Scientists from the Dresden University of Technology (Germany), M. Löhle et al., reported their study results in the December 28th online edition of Stem Cells. The investigators conducted experiments comparing the efficiency of neuronal differentiation from induced pluripotent stem cells (iPSCs) which were generated from postnatal murine neural stem cells (NSCs) transduced with either one (Oct4) or two (Oct4 and Klf4) reprogramming factors and compared their level of neuronal differentiation efficiency with embryonic stem cells (ESCs) and iPSCs generated from fibroblasts with all four reprogramming factors (Oct4, Klf4, c-Myc, and Sox2). The experimental results revealed that neuronal differentiation from neural stem cells transduced with one or two reprogramming factors were less efficient than ESCs or iPSCs produced with 4 transcrpition factors. The researchers also note that similar results were "obtained after hematoendolthelial differentition on OP9 bone marrow stromal cells, where factor-reduced iPSCs generated lower proportion of colonies with hematoendolthelial progenitors than colonies of ESC," iPSC (generated from NSCs with 4 factors) and iPSCs generated from hematoendolthelial cells with 4 reprogramming factors. The authors concluded from their observtion "that a reduction of reprogramming factors does not only reduce reprogramming efficiency, but may also worsen subsequent differentiation and hinder future application of iPSCs in cell replacement therapies."

In the December 28th online edition of Stem Cells, S. G. Ball et al. from the University of Manchester (U.K.) reported their study results the role of platelet-derived growth factor receptor (PDGFR) signaling on controlling the fate of human mesenchymal stem cells (hMSCs). With a small molecule PDGFR inhibitor, the investigators observed rounding of MSCs concomitant with upregulation in the expression of Oct4 and Nanog. The experimental data suggested that PDGFR signaling inhibition resulted in JAK, MEK, and EGFR signaling modulating MSC differentiation. Also, the PDGFR inhibitor-treated MSC were observed to express endodermal, ectodermal and mesodermal markers which enhanced their "potency." The authors concluded from their study results that "inhibiting these specific receptor tyrosine kinases, which play essential roles in tissue formation, offers a novel approach to unlock the therapeutic capacity of MSCs."

In the December 12th online edition of Stem Cells, E. Narva et al. from University of Turku (Finland), published their experimental results correlating regulatory process for human embryonic stem cells (hESCs) to self-renew and the disruptive process that can result in neoplastic cells. The investigators discovered a stem cell specific RNA binding protein, L1TD1, whose expression results in hESC self-renewal and cancer cell proliferation. The study revealed that depleting L1TD1 leads to downregulation of Oct4 and Nanog. The researchers also found that L1TD1 is highly expressed in seminomas and its depletion in the cancer cells inhibits self=renewal and their prolfieration. It appear L1TD1 interacts with microRNA Lin28 and RNA helicaseA (RHA) which in turn regulates the translation of Oct4. From their experimental observations, the atuhors hypothesized that "L1TD1 is part of the L1TD1-RHA complex that influence levels of Oct4."

In the November 30th online edition of Stem Cells, S.-C. Yu et al. from the Third Military Medical University (Chongqing, China) reported their study findings on the role of the gap junctional intercellular communication (GJIC) in modulating the malignant behaviour of cancer stem cells. The investigators compared the GJIC of glioma stem cells (GSCs) derived from tumorspheres to adherent GSCs. Although all GSCs had reduced GJIC, the experimental data revealed more gap junction-like structures in differentiated GSCs than in GSCs. The researchers found that GSCs expressed very low levels of connexin 43 (Cx43) concomitant with hypermethylation in the promoter for gap junction protein α1 (GJA1). Additionally, re-expression of Cx43 in GSCs inhibited their ability to self-renew as well as decreasing their invasive and tumorigenic potential. It was also shown that Cx43 expression upregulated E-cadherin gene expression concomitant with changes in Wnt/β-catenin expression. The authors concluded that their "results suggest that GSCs require low expression of Cx43 for maintaining their malignant phenotype, and up-regulation of Cx43 might be a potential strategy for treatment of malignant glioma."