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Stem Cell Research

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https://www.readbyqxmd.com/read/28314201/inhibition-of-mirna-212-132-improves-the-reprogramming-of-fibroblasts-into-induced-pluripotent-stem-cells-by-de-repressing-important-epigenetic-remodelling-factors
#1
Nils Pfaff, Steffi Liebhaber, Selina Möbus, Abbas Beh-Pajooh, Jan Fiedler, Angelika Pfanne, Axel Schambach, Thomas Thum, Tobias Cantz, Thomas Moritz
MicroRNAs (miRNAs) repeatedly have been demonstrated to play important roles in the generation of induced pluripotent stem cells (iPSCs). To further elucidate the molecular mechanisms underlying transcription factor-mediated reprogramming we have established a model, which allows for the efficient screening of whole libraries of miRNAs modulating the generation of iPSCs from murine embryonic fibroblasts. Applying this model, we identified 14 miRNAs effectively inhibiting iPSC generation, including miR-132 and miR-212...
March 7, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28257933/genetic-ablation-of-the-mammalian-sterile-20-like-kinase-1-mst1-improves-cell-reprogramming-efficiency-and-increases-induced-pluripotent-stem-cell-proliferation-and-survival
#2
Abigail Robertson, Tamer M A Mohamed, Zeinab El Maadawi, Nicholas Stafford, Thuy Bui, Dae-Sik Lim, Elizabeth J Cartwright, Delvac Oceandy
Adult fibroblasts can be reprogrammed into induced pluripotent stem cells (iPSC) for use in various applications. However, there are challenges in iPSC generation including low reprogramming efficiency, yield, cell survival and viability. Since the Hippo signalling pathway is a key pathway involved in regulating cell proliferation and survival, we here test whether modification of the Hippo pathway will enhance the efficiency of iPSC generation and improve their survival. The Hippo pathway was modified by genetic ablation of the mammalian sterile-20 like kinase 1 (Mst1), a major component of the pathway...
February 27, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28249229/differentiation-and-characterization-of-rhesus-monkey-atrial-and-ventricular-cardiomyocytes-from-induced-pluripotent-stem-cells
#3
Xiaoqian Zhang, Henghua Cao, Shuyun Bai, Weibang Huo, Yue Ma
The combination of non-human primate animals and their induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) provides not only transplantation models for cell-based therapy of heart diseases, but also opportunities for heart-related drug research on both cellular and animal levels. However, the subtypes and electrophysiology properties of non-human primate iPSC-CMs hadn't been detailed characterized. In this study, we generated rhesus monkey induced pluripotent stem cells (riPSCs), and efficiently differentiated them into ventricular or atrial cardiomyocytes by modulating retinoic acid (RA) pathways...
February 11, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28232155/modeling-glanzmann-thrombasthenia-using-patient-specific-ipscs-and-restoring-platelet-aggregation-function-by-cd41-overexpression
#4
Liang Hu, Lili Du, Yan Zhao, Wen Li, Qi Ouyang, Di Zhou, Guangxiu Lu, Ge Lin
Glanzmann thrombasthenia (GT) is a rare monogenic hemorrhagic disorder involving aggregation defect of non-nuclear platelets. In this study we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of a GT patient with complex heterogeneous mutations of ITGA2B gene. GT-iPSCs could be successfully differentiated into platelets (GT-iPS-platelets). GT-iPS-platelets were CD41-/CD42b+/CD61- and were platelet activation marker (PAC-1) negative after adenosine diphosphate (ADP) activation. Furthermore, GT-iPS-platelets were defective in platelet aggregation tests in vitro...
February 11, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28192743/behavior-of-leucine-rich-repeat-containing-g-protein-coupled-receptor-5-expressing-cells-in-the-reprogramming-process
#5
Yuko Arioka, Hiroyasu Ito, Akihiro Hirata, Katsunori Semi, Yasuhiro Yamada, Mitsuru Seishima
It remains unclear what cells are proper for the generation of induced pluripotent stem cells (iPSCs). Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is well known as a tissue stem cell and progenitor marker, both of which are reported to be sensitive to reprogramming. In the present study, we examined the reprogramming behavior of Lgr5-expressing cells (Lgr5+ cells). First, we compared reprogramming behavior using mouse Lgr5+ and Lgr5 negative (Lgr5-) hair follicles (HFs). The number of alkaline phosphatase staining-positive cells was lesser in a well of Lgr5+ HFs than in Lgr5- HFs; however, the ratio of Nanog+ SSEA1+ cells in the cell mixture derived from Lgr5+ HFs was much higher than that from Lgr5- HFs...
February 4, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28174013/update-on-fertility-restoration-from-prepubertal-spermatogonial-stem-cells-how-far-are-we-from-clinical-practice
#6
Maria Grazia Giudice, Francesca de Michele, Jonathan Poels, Maxime Vermeulen, Christine Wyns
Fertility preservation in prepubertal boys facing gonadotoxic treatment is still at the experimental stage. Nevertheless cryopreservation of immature testicular tissue (ITT) obtained by small testicular biopsy is being increasingly proposed in reproductive care clinics for this purpose. Different approaches to in vivo or in vitro mature spermatogonial stem cells (SSCs) contained in ITT have been studied: autografting of testicular tissue pieces, transplantation of one's own purified germ cell suspensions, and in vitro maturation (IVM) for subsequent use of sperm for intra cytoplasmic sperm injection (ICSI)...
February 2, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28110125/chemical-defined-and-albumin-free-generation-of-human-atrial-and-ventricular-myocytes-from-human-pluripotent-stem-cells
#7
Fei Pei, Junjie Jiang, Shuyun Bai, Henghua Cao, Luyang Tian, Ya Zhao, Chuanxiu Yang, Haiheng Dong, Yue Ma
Most existing culture media for cardiac differentiation of human pluripotent stem cells (hPSCs) contain significant amounts of albumin. For clinical transplantation applications of hPSC-derived cardiomyocytes (hPSC-CMs), culturing cells in an albumin containing environment raises the concern of pathogen contamination and immunogenicity to the recipient patients. In addition, batch-to-batch variation of albumin may cause the inconsistent of hPSC cardiac differentiation. Here, we demonstrated that antioxidants l-ascorbic acid, trolox, N-acetyl-l-cysteine (NAC) and sodium pyruvate could functionally substitute albumin in the culture medium, and formulated an albumin-free, chemical-defined medium (S12 medium)...
January 12, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28086122/increasing-the-physical-size-and-nucleation-status-of-human-pluripotent-stem-cell-derived-ventricular-cardiomyocytes-by-cell-fusion
#8
Chi-Wing Kong, Shuxun Chen, Lin Geng, Angie Man-Yee Shum, Dong Sun, Ronald A Li
Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) provide an unlimited source of donor cells for potential cardiac regenerative therapies. However, hPSC-CMs are immature. For instance, hPSC-CMs are only 1/10 of the physical size of their adult counterparts; the majority are mono- rather than bi- or multi-nucleated, which is an evolutionary adaptive feature in metabolically active cells such as adult CMs. Here, we attempted to increase the physical size and nucleation status of hPSC-derived ventricular (V) cardiomyocytes (hPSC-VCMs) using chemically-induced cell fusion, and examined the subsequent functional effects...
January 6, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28088038/evidence-of-functional-duplicity-of-nestin-expression-in-the-adult-mouse-midbrain
#9
Parisa Farzanehfar, Shi Sheng Lu, Anupa Dey, Dharshani Musiienko, Hamzah Baagil, Malcolm K Horne, Tim D Aumann
Whether or not neurogenesis occurs in the adult substantia nigra pars compacta (SNc) is an important question relevant for developing better treatments for the motor symptoms of Parkinson's disease (PD). Although controversial, it is generally believed that dividing cells here remain undifferentiated or differentiate into glia, not neurons. However, there is a suggestion that Nestin-expressing neural precursor cells (NPCs) in the adult SNc have a propensity to differentiate into neurons, which we sought to confirm in the present study...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28073086/human-neural-progenitors-derived-from-integration-free-ipscs-for-sci-therapy
#10
Ying Liu, Yiyan Zheng, Shenglan Li, Haipeng Xue, Karl Schmitt, Georgene W Hergenroeder, Jiaqian Wu, Yuanyuan Zhang, Dong H Kim, Qilin Cao
As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28076753/cd25-targeted-therapy-of-chemotherapy-resistant-leukemic-stem-cells-using-dr5-specific-trail-peptide
#11
Jayaprakasam Madhumathi, Surapally Sridevi, Rama Shanker Verma
Chemotherapy resistant leukemic stem cells (LSCs) are being targeted as a modern therapeutic approach to prevent disease relapse. LSCs isolated from methotrexate resistant side population (SP) of leukemic cell lines HL60 and MOLT4 exhibited high levels of CD25 and TRAIL R2/DR5 which are potential targets. Recombinant immunotoxin conjugating IL2α with TRAIL peptide mimetic was constructed for DR5 receptor specific targeting of LSCs and were tested in total cell population and LSCs. IL2-TRAIL peptide induced apoptosis in drug resistant SP cells from cell lines and showed potent cytotoxicity in PBMCs derived from leukemic patients with an efficacy of 81...
January 4, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28171825/ex-vivo-expansion-of-cd3-depleted-cord-blood-mncs-in-the-presence-of-bone-marrow-stromal-cells-an-appropriate-strategy-to-provide-functional-nk-cells-applicable-for-cellular-therapy
#12
Ehteramolsadat Hosseini, Mehran Ghasemzadeh, Maedeh Kamalizad, Anthony P Schwarer
Considering umbilical cord blood (UCB) as a rich source of hematopoietic stem cells, we introduced a cost-effective approach to expand CD3(depleted) UCB-MNCs into functional NK cells. CD3(depleted) UCB-MNCs were expanded in the presence or absence of a feeder [bone marrow stem cells (BMSCs) or osteoblasts], with or without cytokines and their differentiation into NK cells was determined by flow cytometry. NK cell function was quantified by LAMP-1/CD107a expression, TNF-α/IFN-γ release, and LDH release/PI staining in targets...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28167342/cellular-transformation-of-human-mammary-epithelial-cells-by-satb2
#13
Wei Yu, Yiming Ma, Augusto C Ochoa, Sharmila Shankar, Rakesh K Srivastava
Breast tumors are heterogeneous and carry a small population of progenitor cells that can produce various subtypes of breast cancer. SATB2 (special AT-rich binding protein-2) is a newly identified transcription factor and epigenetic regulator. It is highly expressed in embryonic stem cells, but not in adult tissues, and regulates pluripotency-maintaining factors. However, the molecular mechanisms by which SATB2 induces transformation of human mammary epithelial cells (HMECs) leading to malignant phenotype are unknown...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28135684/evaluation-of-the-immunogenicity-of-human-ips-cell-derived-neural-stem-progenitor-cells-in-vitro
#14
Masahiro Ozaki, Akio Iwanami, Narihito Nagoshi, Jun Kohyama, Go Itakura, Hiroki Iwai, Soraya Nishimura, Yuichiro Nishiyama, Soya Kawabata, Keiko Sugai, Tsuyoshi Iida, Kohei Matsubayashi, Miho Isoda, Rei Kashiwagi, Yoshiaki Toyama, Morio Matsumoto, Hideyuki Okano, Masaya Nakamura
To achieve the goal of a first-in-human trial for human induced pluripotent stem cell (hiPSC)-based transplantation for the treatment of various diseases, allogeneic human leukocyte antigen (HLA)-matched hiPSC cell banks represent a realistic tool from the perspective of quality control and cost performance. Furthermore, considering the limited therapeutic time-window for acute injuries, including neurotraumatic injuries, an iPS cell bank is of potential interest. However, due to the relatively immunoprivileged environment of the central nervous system, it is unclear whether HLA matching is required in hiPSC-derived neural stem/progenitor cell (hiPSC-NS/PC) transplantation for the treatment of neurodegenerative diseases and neurotraumatic injuries...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28131957/the-role-of-methylation-dna-polymorphisms-and-micrornas-on-hla-g-expression-in-human-embryonic-stem-cells
#15
A Verloes, C Spits, M Vercammen, M Geens, J LeMaoult, K Sermon, W Coucke, H Van de Velde
The human leukocyte antigen (HLA)-G gene seems to play a pivotal role in maternal tolerance to the fetus. Little is known about HLA-G expression and its molecular control during in vivo human embryogenesis. Human embryonic stem cells (hESC) provide an interesting in vitro model to study early human development. Different studies reported discrepant findings on whether HLA-G mRNA and protein are present or absent in hESC. Several lines of evidence indicate that promoter CpG methylation and 3' untranslated region (3'UTR) polymorphisms may influence HLA-G expression...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28129601/pluripotent-cells-display-enhanced-resistance-to-mutagenesis
#16
Daniel J Cooper, I-Chung Chen, Christine Hernandez, Yufeng Wang, Christi A Walter, John R McCarrey
Pluripotent cells have been reported to exhibit lower frequencies of point mutations and higher levels of DNA repair than differentiated cells. This predicts that pluripotent cells are less susceptible to mutagenic exposures than differentiated cells. To test this prediction, we used a lacI mutation-reporter transgene system to assess the frequency of point mutations in multiple lines of mouse pluripotent embryonic stem cells and induced pluripotent cells, as well as in multiple lines of differentiated fibroblast cells, before and after exposure to a moderate dose of the mutagen, methyl methanesulfonate...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28126658/pluripotency-of-embryo-derived-stem-cells-from-rodents-lagomorphs-and-primates-slippery-slope-terrace-and-cliff
#17
REVIEW
Pierre Savatier, Pierre Osteil, Patrick P L Tam
The diverse cell states and in vitro conditions for the derivation and maintenance of the mammalian embryo-derived pluripotent stem cells raise the questions of whether there are multiple states of pluripotency of the stem cells of each species, and if there are innate species-specific variations in the pluripotency state. We will address these questions by taking a snapshot of our knowledge of the properties of the pluripotent stem cells, focusing on the maintenance of pluripotency and inter-conversion of the different types of pluripotent stem cells from rodents, lagomorphs and primates...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/27984756/non-reconstructable-peripheral-vascular-disease-of-the-lower-extremity-in-ten-patients-treated-with-adipose-derived-stromal-vascular-fraction-cells
#18
Michael H Carstens, Arturo Gómez, Ronald Cortés, Elizabeth Turner, Cecilia Pérez, Marlon Ocon, Diego Correa
We present a series of ten patients with non-reconstructable peripheral vascular disease (PVD), secondary to arteriosclerosis (AS) and/or diabetes mellitus (DM), treated with local injection of non-expanded autologous, adipose-derived stromal vascular fraction (SVF) cells for the purposes of enhancing neovascularization and chronic wound healing. Adipose tissue was surgically harvested and processed to yield the heterogeneous SVF cells for immediate point-of-care injection. The gastrocnemius muscles and ulcers or wounds where present were locally injected with the resulting SVF...
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/27939557/the-administration-of-multipotent-stromal-cells-at-precancerous-stage-precludes-tumor-growth-and-epithelial-dedifferentiation-of-oral-squamous-cell-carcinoma
#19
Flavia Bruna, Martha Arango-Rodríguez, Anita Plaza, Iris Espinoza, Paulette Conget
Multipotent stromal cells (MSCs) are envisioned as a powerful therapeutic tool. As they home into tumors, secrete trophic and vasculogenic factors, and suppress immune response their role in carcinogenesis is a matter of controversy. Worldwide oral squamous cell carcinoma (OSCC) is the fifth most common epithelial cancer. Our aim was to determine whether MSC administration at precancerous stage modifies the natural progression of OSCC. OSCC was induced in Syrian hamsters by topical application of DMBA in the buccal pouch...
January 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28038351/microrna-29-impairs-the-early-phase-of-reprogramming-process-by-targeting-active-dna-demethylation-enzymes-and-wnt-signaling
#20
Mariane Serra Fráguas, Reto Eggenschwiler, Jeannine Hoepfner, Josiane Lilian Dos Santos Schiavinato, Rodrigo Haddad, Lucila Habib Bourguignon Oliveira, Amélia Góes Araújo, Marco Antônio Zago, Rodrigo Alexandre Panepucci, Tobias Cantz
Somatic cell reprogramming by transcription factors and other modifiers such as microRNAs has opened broad avenues for the study of developmental processes, cell fate determination, and interplay of molecular mechanisms in signaling pathways. However, many of the mechanisms that drive nuclear reprogramming itself remain yet to be elucidated. Here, we analyzed the role of miR-29 during reprogramming in more detail. Therefore, we evaluated miR-29 expression during reprogramming of fibroblasts transduced with lentiviral OKS and OKSM vectors and we show that addition of c-MYC to the reprogramming factor cocktail decreases miR-29 expression levels...
December 19, 2016: Stem Cell Research
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