In the December 17th supplement of Cell Transplantation, T. Ma et al. from Tsinghua University (Beijing, China) published their study observations on intracerebral transplantation of adipose-derived mesenchymal stem cells (ADSCs) in transgenic mice with Alzheimer's disease (AD). The investigators conducted a study to determine if ADSCs transplantation in AD mice and their immunomodulatory effects on microglial cells. The experimental results showed that ADSC transplantation dramatically reduced b-amyloid (Ab) peptide deposition in the hippocampus and cortex of mouse brains. The researchers also observed dramatic improvement in learning and memory function post ADSC transplantation. Additionally, activated microglial cells were observed to surround preferentially and infiltrate the Ab plaques in both the hippocampus and cortex. The microglia had adopted an alternative activated phenotype with decreased expression levels of pro-inflammatory cytokines (TNF-a and IL-1b) and an increase in levels of alternative activation markers (IL-4 and ARG1) and Ab degradation enzymes. The authors concluded from their study results that "ADSC transplantation could modulate microglial activation in AD mice, mitigate AD symptoms, and alleviate cognitive decline...which suggest ADSC transplantation as a promising choice for AD therapy."
In the December 5th online early publication of PNAS, K. F. Au et al. from Stanford University published their study results on identification of isoforms expressed by human genes associated with tissue-specific functions. The investigators used a combination of both second and third generation RNA-Sequencing (RefSeq) in identifying isoforms in human embryonic stem cells (hESCs). The isoform dataset revealed 8,084 full-length isoforms and 5,459 isoforms predicted by statistical inference. Analysis of the dataset showed 273 RNAs from gene loci that have not been previously identified. Additionally, characterization of the novel loci uncovered a subset of genes expressed in "pluripotent cells, but not in diverse fetal and adult tissues;" which appears to perturb "network of pluripotency-associated genes." The authors concluded from their results which "suggest that gene identification, even in well-characterized human cell lines and tissues, is likely far from complete."
In the November 20th online early publication of PNAS, M. Koyanagi-Aoi et al. from Kyoto University (Japan) reported their study results on comparing the molecular signatures and differentiation properties between embryonic stem cells (ESCs) and human induced pluripotent stem cells (hiPSCs). The investigators found overlapping variations in gene expression and DNA methylation among ESCs and hIPSCs clones which had been differentiated in vitro into neural progenitors. The experimental results also revealed seven of the hiPSC clones "retained a significant number of undifferentiated cells after neural differentiation. These differentiated neural stem cells formed teratomas when transplanted into mouse brains." The researchers found that the differentiation-defective hiPSCs had higher expression of several genes which included expression of long terminal repeats of human endogenous retroviruses. The authors concluded from their experimental results that their data "demonstrated a subset of hiPSC lines that have aberrant gene expression and defective potential in neural differentiation, which need to be identified and eliminated before applications in regenerative medicine."
In the December issue of Cell Stem Cell, Y. S. Choi et al. from the University of Pennsylvania Perelman School of Medicine reported their study results on the role of Wnt/b-catenin signaling on hair follicle stem cells. The investigators performed deletion of b-catenin either in skin epithelia, hair follicle stem cells, or interfollicular epidermis and comparing the phenotypes caused by ectopic expression of the Wnt/b-catenin inhibitor, Dkk1. LRP (Wnt co-receptor lipoprotein receptor-related protein). The experimental data revealed that LRP inhibition allows for stem cell survival and blocks hair growth. However, "b-catenin is required in the bulge stem cells for their proliferation, but not survival." The researchers concluded the latter observation indicates "persistence of functional progenitors. The study results also demonstrated that removal of Dkk1, as ectopic inhibitor, hair follicle cells continue to proliferate. b-catenin signaling was also shown to contribute to proliferation of interfollicular epidermis "under homeostatic, but not inflammatory, conditions."
In the December issue of Stem Cell Research & Therapy, W.-J. Zhange et al. from China-Japan Friendship Hospital (Beijing, China) published their study results on expanding and differentiating human fetal pancreatic progenitor cells into insulin-producing cells. The investigators expanded the fetal progenitor cells in a culture medium containing fibroblast growth factor (bFGF) and leukemia inhibitor factor (LIF). Following ex vivo expansion, the pancreatic progenitor cells were differentiated into insulin-producing cells with nicotinamide, all-trans retinoic acid, glucagon-like peptide-1, and activin A (introduced during the last week of cultivation). The researchers found ha the differentiated cells expressed insulin, glucagon, glucose transporter 1(GLUT1), GLUT2, and voltage-dependent calcium channel (VDCC). Additionally, the experimental results demonstrated that the aggregated islet-like structures expressed higher level of insulin than adherent monolayer cultures. The aggregated cells transplanted into diabetic nude mice maintained normoglycemia. The authors concluded from their study results that "human fetal pancreatic progenitor cells have a good capacity for generating producing cells and provide a promising potential source for diabetes treatment."
In the November 8th online early publication of Stem Cells, X. Li et al. from Massachusetts General Hospital reported their experimental results on the role of the Krüppel-like transcription factor ZBP-89 (Zfp148) in hematopoiesis of adult mouse hematopoietic stem/progenitor cells (HSPCs). The investigators performed conditional deletion of ZBP-89 in HSPCs which results in anemia and thrombocytopenia; particularly, after chemically induced erythro/megakaryopoietic stress. Additionally, bone marrow transplantation of ZBP89-/- HSPC resulted in myeloid-to-B lymphoid switch in the bone marrow recipients. In vitro experiments demonstrated that myeloid-to-B lymphoid switch is associated with the up-regulation of PU.1 and down-regulation of SCL/Tal1 and GATA-1 in ZBP-89 deficient cells. The researchers further demonstrated that ZBP-89 is a direct repressor of PU.1 and activator of SCL/Tal1 and GATA-1. The authors concluded that their experimental results demonstrated the role of "ZBP-89 in regulating stress hematopoiesis in adult mouse bone marrow."
In the November 21st advanced online publication of Cell Stem Cell, R. Le et al. from China Agricultural University (Beijing, China) reported their experimental results comparing somatic cell nuclear transfer (SCNT) in rejuvenating telomeres in telomerase-deficient (Terc-/-) mice. The investigators found that embryonic stem cells derived from SCNT (Terc-/- ntESCs) embryos have greater differentiation potential than Terc-/- iPSCs. Telomere lengthening and capping are more active in the Terc-/-ntESCs. Additionally, mitochondria function is severly impairs in Terc-/- iPSCs which limits their differentiation potential. Conversely, mitochondria function is significantly improved in Terc-/- ntESCs. The authors concluded from their study results that "SCNT-mediated reprogramming mitigates telomere dysfunction and mitochondrial defects to a greater extent than iPSC-based reprogramming. Understanding the basis of this differential could help optimize reprogramming strategies."
In the November 8th online early publication of Stem Cells, A. Richter et al. from University of Iceland published their experimental results on the underlying mechanism(s) in which bone morphogenetic protein initiate differentiation in human embryonic stem cells (hESCs). The investigators found that the transcription factors SLUG and MSX2 which are involved in Epithelial-Mesenchymal Transition (EMT) are important mediators of BMP4 induced differentiation. SLUG and MSX2 are also involved in gastrulation during embryonic development and tumor progression. BMP was shown to target SLUG which results in phosphorylated Smad1/5/8 co-localizing with the SLUG protein and differentiation along the edges of hESC colonies. Knockdown of SLUG by shRNA blocked BMP mediated mesodermal differentiation. The authors also noted from their study results that "BMP4 induced MSX expression results in mesodermal formation and preferential differentiation towards the cardiovascular lineage."
In the November 17th early online publication of Nature Biotechnology, L. Baeyens et al. from the University of California, San Francisco published their experimental results on using cytokines to reprogram pancreatic exocrine (acinar) cells into beta-like cells. The investigators administered epidermal growth factor and ciliary neutrophic factor into adult mice with chronic hyperglycemia. Epigenetically reprogramming of terminally differentiated acinar resulted in the generation of functional beta-like cells which were glucose responsive. The treated diabetic mice were able to maintain normoglycemia for up to 248 days. The researchers found that reprogramming of acinar cells were dependent upon Stat3 signaling and a threshold number of Neurogenin 3 (Ngn3)-expressing acinar cells. The authors concluded from their experimental observation that their approach of transient exposure of cytokines in vivo was a more efficient method for reprogramming acinar-to-beta cell than using viral vectors for delivering exogenous transcription factors.
In the December issue of Stem Cells Translational Medicine, S. S. Bedi et al. from the University of Texas, Houston reported their study results on the mechanism by which intravenous infusion of bone marrow-drived multipotent adult progenitor cells (MAPCs) attenuates inflammation following traumatic brain injury (TBI) in rodents. The investigators infused MAPCs (2 and 10 million cells per kilogram) 2 and 24 hours after cortical contusion injury (CCI). The experimental data revealed that the rats receiving 10 million MAPCs (CCI-10) had significant improvement in motor function and improved memory. The researchers also observed signification decrease in the number of activated microglia cells in the dentate gyrus inf the CCI-10 group compared to controls. The authors concluded that their "results demonstrate that intravenous MAPC treatment after TBI in a rodent model offers long-term improvement in spatial learning as well as attenuation of neuroinfammation."