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Stem Cells and Development

Carmela Nardelli, Ilaria Granata, Laura Iaffaldano, Valeria D'Argenio, Valentina Del Monaco, Giuseppe Maria Maruotti, Daniela Omodei, Luigi Del Vecchio, Pasquale Martinelli, Francesco Salvatore, Mario Rosario Guarracino, Lucia Sacchetti, Lucio Pastore
Clinical findings and data obtained in animal models indicate that nutrient uptake and exposure to environmental agents during pregnancy may affect fetal/newborn gestational programming thereby resulting in obesity and/or obesity-related disorders in offspring. Human amniotic mesenchymal stem cells (hA-MSCs) differentiate into adipocytes, and are thus a suitable model to investigate adipocyte functions in obesity. The aim of this study was to elucidate the miRNome of hA-MSCs and its contribution to obesity in pregnancy...
October 20, 2016: Stem Cells and Development
Zhong Liu, Cheng Zhang, Alireza Khodadadi-Jamayran, Lam Dang, Xiaosi Han, Kitai Kim, Hu Li, Rui Zhao
Neural stem cells (NSCs) have the capacity to differentiate into neurons, astrocytes, and oligodendrocytes, and therefore represent a promising donor tissue source for treating neurodegenerative diseases and repairing injuries of the nervous system. However, it remains unclear how canonical microRNAs (miRNAs), the subset of miRNAs requiring the Drosha-Dgcr8 microprocessor and the type III RNase Dicer for biogenesis, regulate NSCs. In this study, we established and characterized <i>Dgcr8</i><sup>-/-</sup> NSCs from conditionally <i>Dgcr8</i>-disrupted mouse embryonic brain...
October 20, 2016: Stem Cells and Development
Amanda Faria Assoni, Giuliana Castello, Marcos Valadares, Melinda Beccari, Juliana Gomes, Mayra Pelatti, Miguel Mitne-Neto, Valdemir Melechco Carvalho, Mayana Zatz
Duchenne muscular dystrophy (DMD) is a lethal X-linked disorder caused by null mutations in the dystrophin gene. Although the primary defect is the deficiency of muscle dystrophin, secondary events, including chronic inflammation, fibrosis and muscle regeneration failure are thought to actively contribute to disease progression. Despite several advances, there is still no effective therapy for DMD. Therefore, the potential regenerative capacities, as well as immune-privileged properties of Mesenchymal Stromal Cells (MSCs), have been the focus of intense investigation in different animal models aiming the treatment of these disorders...
October 20, 2016: Stem Cells and Development
Shery Park, Hu Zhao, Mark Urata, Yang Chai
Repair of calvarial bony defects remains challenging for craniofacial surgeons. Injury experiments on animal calvarial bones are widely used to study healing mechanisms and test tissue engineering approaches. Previously we identified Gli1+ cells within the calvarial sutures as stem cells supporting calvarial bone turnover and injury repair. In this study, we tested the regenerative capacity of the suture region compared to other areas of calvarial bone. Injuries were made to mouse sagittal sutures or other areas of the calvarial bone at varying distances from the suture...
October 20, 2016: Stem Cells and Development
Ashley I Beyer, Marcus O Muench
Immunodeficient mice play a critical role in hematology research as in vivo models of hematopoiesis and immunology. Multiple strains have been developed, but hematopoietic stem cell engraftment and immune reconstitution have not been methodically compared among them. Four mouse strains were transplanted with human fetal bone marrow or adult peripheral blood CD34+ cells: NSG, NSG-3GS, hSCF-Tg-NSG and hSIRPα-DKO. Hematopoietic engraftment in the bone marrow, blood, spleen and liver was evaluated by flow cytometry 12 weeks after transplant...
October 19, 2016: Stem Cells and Development
Drake J Smith, Levina J Lin, Heesung Moon, Alexander T Pham, Xi Wang, Siyuan Liu, Sunjong Ji, Valerie Rezek, Saki Shimizu, Marlene Ruiz, Jennifer Lam, Deanna M Janzen, Sanaz Memarzadeh, Donald B Kohn, Jerome A Zack, Scott G Kitchen, Dong Sung An, Lili Yang
The humanized bone marrow-liver-thymus (BLT) mouse model harbors a nearly complete human immune system, therefore providing a powerful tool to study human immunology and immunotherapy. However, its application is greatly limited by the restricted supply of human CD34(+) hematopoietic stem cells and fetal thymus tissues that are needed to generate these mice. The restriction is especially significant for the study of human immune systems with special genetic traits, such as certain human leukocyte antigen (HLA) haplotypes or monogene deficiencies...
October 18, 2016: Stem Cells and Development
Marina Cavazzana, Jean-Antoine Ribeil, Chantal Lagresle-Peyrou, Isabelle André-Schmutz
When considering inherited diseases that can be treated by gene transfer into Hematopoietic stem cells (HSCs), there are only two in which the HSC and progenitor cell distribution inside the bone marrow and its microenvironment are exactly the same as in a healthy subject: metachromatic leukodystrophy (MLD) and ALD. In all other settings (X-linked severe combined immunodeficiency (SCID-X1), adenosine deaminase deficiency, Wiskott-Aldrich syndrome and β-hemoglobinopathies), the bone marrow content of the different stem and precursor cells and the cells' relationship with the stroma have very specific characteristics...
October 17, 2016: Stem Cells and Development
Forrest T Goodfellow, Blanka Tesla, Gregory Simchick, Qun Zhao, Thomas Hodge, Melinda A Brindley, Steven L Stice
The explosive spread of the Zika virus (ZIKV) through South and Central America has been linked to an increase in congenital birth defects, specifically microcephaly. Representative rodent models for investigating infections include direct central nervous system (CNS) injections late in pregnancy and transplacental transmission in immunodeficient mice. Microcephaly in humans may be the result of infection occurring early in pregnancy, therefore recapitulating that the human course of ZIKV infection should include normal embryo exposed to ZIKV during the first trimester...
October 17, 2016: Stem Cells and Development
Ateka Khader, Lauren S Sherman, Pranela Rameshwar, Treena L Arinzeh
Articular cartilage has a limited ability to heal. Mesenchymal stem cells (MSCs) derived from the bone marrow have shown promise as a cell type for cartilage regeneration strategies. In this study, sodium tungstate (Na2WO4), which is an insulin mimetic, was evaluated for the first time as an inductive factor to enhance human MSC chondrogenesis. MSCs were seeded onto three-dimensional electrospun scaffolds in growth medium (GM), complete chondrogenic induction medium (CCM) containing insulin, and CCM without insulin...
October 17, 2016: Stem Cells and Development
Urszula Polak, Yanjie Li, Jill Sergesketter Butler, Marek Napierala
Friedreich's ataxia (FRDA) is the most common autosomal recessive ataxia. This severe neurodegenerative disease is caused by an expansion of guanine-adenine-adenine (GAA) repeats located in the first intron of the frataxin (FXN) gene, which represses its transcription. Although transcriptional silencing is associated with heterochromatin-like changes in the vicinity of the expanded GAAs, the exact mechanism and pathways involved in transcriptional inhibition are largely unknown. As major remodeling of the epigenome is associated with somatic cell reprogramming, modulating chromatin modification pathways during the cellular transition from a somatic to a pluripotent state is likely to generate permanent changes to the epigenetic landscape...
October 17, 2016: Stem Cells and Development
Laila Noli, Antonio Capalbo, Yaser Dajani, Danilo Cimadomo, Jean Bvumbe, Laura Rienzi, Filippo Maria Ubaldi, Caroline Ogilvie, Yacoub Khalaf, Dusko Ilic
Studies reporting term pregnancy and the production of genetically identical offspring from isolated blastomeres of early stage embryos have been carried out in small and large animals. However, very little is known about the effects of embryo splitting on the development and reproductive competency of human embryos. In this study, we investigated the effects of embryo splitting on profile of microRNAs (miRNAs) detected in their spent blastocyst medium (SBM) by comparative analysis of miRNA profiles in SBM of human twin embryos created by blastomere biopsy and SBM of blastocysts that resulted in a healthy pregnancy and live birth following embryo transfer...
October 17, 2016: Stem Cells and Development
Lei Hu, Ying Wen, Junji Xu, Tingting Wu, Chunmei Zhang, Jinsong Wang, Jie Du, Songlin Wang
Mesenchymal stem cell (MSC)-mediated bone regeneration is used to replace lost bone. However, methods to accelerate the process and stabilize regenerated bone remain limited. Therefore, we investigated the effect of bisphosphonates (BPs) on the function of bone marrow mesenchymal stem cells (BMMSCs) to determine if they might enhance MSC-mediated bone regeneration. We isolated and cultured BMMSCs from BALB/c mice and treated the cells with 0.1, 0.5, 1, 5, or 10 μM zoledronic acid (ZA; Zometa, a commercially available BP)...
October 13, 2016: Stem Cells and Development
Maurizio Pesce, Elisa Messina, Isotta Chimenti, Antonio Paolo Beltrami
The life-long story of the heart starts concomitantly with primary differentiation events occurring in multipotent progenitors located in the so called heart tube. This initially tubular structure starts a looping process which leads to formation of the final four chambered heart with a primary contribution of geometric and position-associated cell sensing. While this establishes the correct patterning of the final cardiac structure, it also feedbacks to fundamental cellular machineries controlling proliferation and differentiation, thus ensuring a coordinated restriction of cell growth and a myocyte terminal differentiation...
October 13, 2016: Stem Cells and Development
Kana Yanagihara, Yujung Liu, Kei Kanie, Kazuo Takayama, Minako Okamura, Mitsuhi Hirata, Takayuki Fukuda, Mika Suga, Hiroki Nikawa, Hiroyuki Mizuguchi, Ryuji Kato, Miho K Furue
Functional hepatocytes derived from human pluripotent stem cells (hPSCs) have potential as tools for predicting drug-induced hepatotoxicity in the early phases of drug development. However, the propensity of hPSC lines to differentiate into specific lineages is reported to differ. The ability to predict low propensity of hPSCs to differentiate into hepatocytes would facilitate the selection of useful hPSC clones and substantially accelerate development of hPSC-derived hepatocytes for pharmaceutical research...
October 12, 2016: Stem Cells and Development
Leilei Zhong, Xiaobin Huang, Emilie Dooms Rodrigues, Jeroen Leijten, Theo Verrips, Mohamed El Khattabi, Marcel Karperien, Janine N Post
Hypertrophic differentiation occurs during in vitro chondrogenesis of mesenchymal stem cells (MSCs), decreasing the quality of the cartilage construct. Previously we identified WNT pathway antagonists Dickkopf 1 homolog (DKK1) and frizzled-related protein (FRZB) as key factors in blocking hypertrophic differentiation of hMSCs. In this study, we investigated the role of endogenously expressed DKK1 and FRZB in chondrogenesis of hMSC, chondrocyte redifferentiation and in preventing cell hypertrophy using three relevant human cell based systems, isolated hMSCs, isolated primary human chondrocytes (hChs), and co-cultures of hMSCs with hChs for which we specifically designed neutralizing nano-antibodies...
October 12, 2016: Stem Cells and Development
Mi-Young Son, Young-Dae Kim, Binna Seol, Mi-Ok Lee, Hee-Jun Na, Bin Yoo, Jae-Suk Chang, Yee Sook Cho
Behçet's disease (BD) is a chronic inflammatory and multisystemic autoimmune disease of unknown etiology. Due to the lack of a specific test for BD, its diagnosis is very difficult, and therapeutic options are limited. Induced pluripotent stem cell (iPSC) technology, which provides inaccessible disease-relevant cell types, opens a new era for disease treatment. Here, we generated BD iPSCs from patient somatic cells and differentiated them into hematopoietic precursor cells (BD iPSC-HPCs) as BD model cells...
October 12, 2016: Stem Cells and Development
I-Chung Chen, Christine Hernandez, Xueping Xu, Austin Cooney, Yufeng Wang, John R McCarrey
Pluripotent stem cells hold the potential to form the basis of novel approaches to treatment of disease in vivo as well as to facilitate the generation of models for human disease, providing powerful avenues to discovery of novel diagnostic biomarkers and/or innovative drug regimens in vitro. However, this will require extensive maintenance, expansion, and manipulation of these cells in culture, which raises a concern regarding the extent to which genetic integrity will be preserved throughout these manipulations...
October 12, 2016: Stem Cells and Development
Laura Barrachina, Ana Rosa Remacha, Antonio Romero, Francisco José Vázquez, Jorge Albareda, Marta Prades, Jaime Gosálvez, Rosa Roy, Pilar Zaragoza, Inmaculada Martín-Burriel, Clementina Rodellar
Mesenchymal stem cells (MSCs) have a great potential for treating equine musculoskeletal injuries. Although their mechanisms of action are not completely known, their immunomodulatory properties appear to be key in their functions. The expression of immunoregulatory molecules by MSCs is regulated by pro-inflammatory cytokines, so inflammatory priming of MSCs might improve their therapeutic potential. However, inflammatory environment could also increase MSC immunogenicity and decrease MSC viability and differentiation capacity...
October 6, 2016: Stem Cells and Development
Lucas Eduardo Botelho de Souza, Tathiane Maistro Malta, Simone Kashima Haddad, Dimas Tadeu Covas
Mesenchymal stem cells (MSC) were initially identified as progenitors of skeletal tissues within mammalian bone marrow and cells with similar properties were also obtained from other tissues such as adipose and dental pulp. Although MSC have been extensively investigated, their native behavior and in vivo identity remains poorly defined. Uncovering the in vivo identity of MSC has been challenging due to the lack of exclusive cell markers, cellular alterations caused by culture methods and extensive focus on in vitro properties for characterization...
October 5, 2016: Stem Cells and Development
R Kumar Pramod, Bo Ram Lee, Young Min Kim, Hong Jo Lee, Young Hyun Park, Tamao Ono, Jeong Mook Lim, Jae Yong Han
We reported previously testis-mediated germline chimera production and characterization of germline stem cell-like cells from chicken testes. The present study aimed to establish an in vitro system for culture of quail spermatogonia stem cells (SSCs) for practical applications in germline preservation and transgenesis. Testicular cells from juvenile (4 weeks old) or adult (8 weeks old) quail testis were isolated using sequential enzymatic digestion. The percentages of viability of isolated testicular cells were 91...
October 5, 2016: Stem Cells and Development
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