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Stem Cells and Development

Fares Ould-Brahim, Sailendra Nath Sarma, Charvi Syal, Kevin Jiaqi Lu, Matthew Seegobin, Anthony Carter, Matthew S Jeffers, Carole Doré, William L Stanford, Dale Corbett, Jing Wang
While transplantation of human induced pluripotent stem cell-derived neural stem cells (hiPSC-NSCs) shows therapeutic potential in animal stroke models, major concerns for translating hiPSC therapy to the clinic are efficacy and safety. Therefore, there is a demand to develop an optimal strategy to enhance the engraftment and regenerative capacity of transplanted hiPSC-NSCs to produce fully differentiated neural cells to replace lost brain tissues. Metformin, an FDA-approved drug, is an optimal neuroregenerative agent that not only promotes NSC proliferation but also drives NSCs toward differentiation...
July 18, 2018: Stem Cells and Development
Anna-Maria Husa, Maria Regina Strobl, Agata Strajeriu, Matthias Wieser, Sabine Strehl, Klaus Fortschegger
Hematopoietic stem and progenitor cells (HSPCs) derived from human induced pluripotent stem cells (hiPSCs) hold great promise for disease modeling, drug screens and eventually cell therapy approaches. During in vitro differentiation of hiPSC into hemato-endothelial progenitors, the emergence of CD34-positive cells indicates a critical step of lineage specification. To facilitate the monitoring of hematopoietic differentiation of hiPSCs, we established fluorescent reporter cells for the stem and progenitor cell marker CD34...
July 16, 2018: Stem Cells and Development
Yong Chen, Jianqi Feng, Shanshan Zhao, Le Han, Hongcheng Yang, Ying Lin, Zhili Rong
Human embryonic stem cells (hESCs) derived 3D lung organoids (HLOs) provide a promising model to study human lung development and disease. HLOs containing proximal or/and immature distal airway epithelial cells have been successfully generated in vitro, such as early staged alveolar type 2 (AT2) cells (SPC+/SOX9+) and immature alveolar type 1 (AT1) cells (HOPX+/SOX9+). When HLOs were transplanted into immunocompromised mice for further differentiation in vivo, only few distal epithelial cells could be observed...
July 16, 2018: Stem Cells and Development
Li Sun, Qianqian Wang, Bin Chen, Yuanyuan Zhao, Bo Shen, Xinlong Wang, Miaolin Zhu, Zhuqian Li, Xiangdong Zhao, Changgen Xu, Zhihong Chen, Mei Wang, Wenrong Xu, Wei Zhu
Several studies show that mesenchymal stem cells (MSCs) homing to tumors not only provide the microenvironment for tumor cells but also promote tumor growth and metastasis. However, the exact mechanism remains unclear. Our study aims to investigate the role of gastric cancer MSCs (GCMSCs)-derived IL15 during GC progression. The effects of IL15 secreted by GCMSCs on GC development were evaluated by detecting the stemness, epithelial-mesenchymal transition (EMT), and migration abilities of GC cell lines. The expression of IL15 in serum and tissues of GC patients was also assessed...
July 16, 2018: Stem Cells and Development
Erica K Low, Egil Brudvik, Bradford Kuhlman, Paul F Wilson, Graça Almeida-Porada, Christopher D Porada
Astronauts on missions beyond low-Earth orbit are exposed to a hostile environment in which they are continually bombarded with unique high-energy species of radiation, while in conditions of microgravity (μG), which can alter radiation response and immunity. In the present studies, we examined the impact exposing human hematopoietic stem/progenitor cells (HSC) to μG had upon their capacity to repair DNA damage and their ability to generate immune cells critical for mounting an effective antitumor response...
July 16, 2018: Stem Cells and Development
Bhairab N Singh, Cyprian Weaver, Mary Garry, Daniel J Garry
Urodele amphibians have a tremendous capacity for the regeneration of appendages including limb and tail following injury. While studies have focused on the cellular and morphological changes during appendicular regeneration, the signaling mechanisms that govern these cytoarchitectural changes during the regenerative response are unclear. Here, we describe the essential role of hedgehog (Hh) and Wnt signaling pathways following tail amputation in the newt. Quantitative PCR (qPCR) studies revealed that members of both the Hh and Wnt signaling pathways including: shh, ihh, ptc-1, wnt-3a, -catenin, axin2, frizzled (frzd)-1, and frzd-2 transcripts were induced following injury...
July 13, 2018: Stem Cells and Development
Soukaina Bahsoun, Karen Coopman, Nicholas R Forsyth, Elizabeth Claire Akam
Most cells in the human body, including human mesenchymal stem cells (hMSCs), have evolved to survive and function in a low, physiological, oxygen (O<sub>2</sub>) environment. Investigators have become increasingly aware of the effects of O<sub>2</sub> levels on hMSC biology and culture and are mimicking the natural niche of these cells in vitro to improve cell culture yields. This presents many challenges in relation to hMSC identity and function and in the maintenance of a controlled O<sub>2</sub> environment for cell culture...
July 13, 2018: Stem Cells and Development
Rika Sakuma, Ai Takahashi, Akiko Nakano-Doi, Rikako Sawada, Saeko Kamachi, Mikiya Beppu, Toshinori Takagi, Shinichi Yoshimura, Tomohiro Matsuyama, Takayuki Nakagomi
Mesenchymal stem cells (MSCs) are multipotent stem cells localized to the perivascular regions of various organs, including bone marrow (BM). While MSC transplantation represents a promising stem-cell based therapy for ischemic stroke, increasing evidence indicates that exogenously administered MSCs rarely accumulate in the injured central nervous system (CNS). Therefore, compared with MSCs, regionally derived brain multipotent stem cells may be a superior source in order to elicit regeneration of the CNS following ischemic injury...
July 12, 2018: Stem Cells and Development
Camille Syrett, Isabel Sierra, Corbett L Berry, Daniel Beiting, Montserrat Anguera
The placenta is a short-lived tissue required for embryonic growth and survival, and it is fetal-derived. Fetal sex influences gestation, and many sexual dimorphic diseases have origins in utero. There is sex-biased gene expression in third trimester human placentas, yet the origin of sex-specific expression is unknown. Here we used an in vitro differentiation model to convert human embryonic stem cells (hESCs) into trophoblastic progenitor cells of the first trimester placenta, which will eventually become mature extravilllous trophoblasts and syncytiotrophoblasts...
July 11, 2018: Stem Cells and Development
Yean Ju Hong, Kwonho Hong, Seki Byun, Hyun Woo Choi, Jeong Tae Do
Pluripotential reprogramming has been examined using various technologies including nuclear transfer, cell fusion, and direct reprogramming. Many studies have used differentiated cells for reprogramming experiments, and nearly all type of somatic cells can acquire pluripotency. However, within the embryo, other cells types are present in addition to somatic cells. The blastocyst stage embryo consists of two main types of cells, inner cell mass and trophectoderm. Trophectoderm cells are the first differentiated form of the totipotent zygote and differ from epiblast cells...
July 11, 2018: Stem Cells and Development
Morteza Zarrabi, Elaheh Afzal, Marzieh Ebrahimi
Self-renewal and multi-potential differentiation are two important features of hematopoietic stem/progenitor cells (HS/PCs) which make them as an ideal source of stem cells for treatment of many hematologic disorders and cancers. Regarding the limited number of cord blood HS/PCs, proper ex vivo expansion can significantly increase the clinical use of cord blood stem cells. Meanwhile, expansion of HS/PCs will be feasible through bypassing the quiescent state of HS/PCs and simultaneously enhancing their proliferative potential and survival while delaying the terminal differentiation and exhaustion...
July 10, 2018: Stem Cells and Development
Kwang Hwan Park, Yoorim Choi, Dong Suk Yoon, Kyoung-Mi Lee, Dohyun Kim, Jin Woo Lee
The crucial trace element zinc stimulates osteogenesis in vitro and in vivo. However, the pathways mediating these effects remain poorly understood. This study aimed to investigate the effects of zinc on osteoblast differentiation in human bone marrow-derived mesenchymal stem cells (hBMSCs) and to identify the molecular mechanisms of these effects. In hBMSCs, zinc exposure resulted in a dose-dependent increase in osteogenesis and increased mRNA and protein levels of the master transcriptional factor RUNX2. Analyzing the upstream signaling pathways of RUNX2, we found that protein kinase A (PKA) signaling inhibition blocked zinc-induced osteogenic effects...
July 9, 2018: Stem Cells and Development
Takeshi Imura, Kei Nakagawa, Yumi Kawahara, Louis Yuge
Recent years have witnessed a rapid increase in space experiments. Initially, scientists focused on understanding the phenomenon of microgravity to discover countermeasures for preventing the adverse effects of microgravity on the astronauts' bodies. Lately, the application of microgravity environment has been gradually increasing with diverse objectives. Protein crystallization and three-dimensional cell culture are typical examples of microgravity application. Our recent studies suggested that microgravity is a useful tool for cell culture in cell-based therapy...
July 6, 2018: Stem Cells and Development
Manuel Delgado Caceres, Christian Pfeifer, Denitsa Docheva
Tendons and ligaments are connective tissues which have been comparatively less studied than muscle and cartilage/bone, even though they are crucial for proper function of the musculoskeletal system. In tendon biology, considerable progress has been made in identifying tendon-specific genes (Scleraxis, Mohawk, and Tenomodulin) in the past decade. However, besides tendon function and the knowledge of a small number of important players in tendon biology, neither the ontogeny of the tenogenic lineage nor signaling cascades have been fully understood...
July 6, 2018: Stem Cells and Development
Luis Marinas-Pardo, Javier Garcia-Castro, Isabel Rodríguez-Hurtado, María Isabel Rodríguez-García, Laura Núñez-Naveira, Manuel Hermida-Prieto
Osteoarthritis (OA) commonly causes lameness in the horse and has a great impact in performance animals. Due to the limitations of current medical therapies, allogenic mesenchymal stem cells (MSCs) may become an alternative method to control inflammation, reduce tissue damage and pain, and therefore improve lameness. We present the results of a regulatory clinical trial testing adipose derived MSCs (Horse Allo 20) in veterinary (Agencia Española del Medicamento y Productos Sanitarios, AEMPS, Spanish Medicines Agency, Reference number 325/ECV) involving a total number of 80 participants and with 90 days of follow-up period...
July 6, 2018: Stem Cells and Development
Kaijian Zhou, Shu Guo, Shuang Tong, Qiang Sun, Fei Li, Xiaowei Zhang, Ying Qiao, Guoxin Liang
Adipose-derived stem cells (ADSCs) are a type of multipotent mesenchymal stem cells (MSCs) with immunosuppressive capacities. However, the underlying mechanisms involved in the inhibitory effects of ADSCs on T cells are not completely elucidated. In this study, human peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3/CD28 antibody-coated beads were cultured with or without allogeneic ADSCs (ADSC-to-PBMC ratio, 1:5). Surface marker levels, violet-labeled cell proliferation, apoptosis, interferon-gamma (IFN-gamma) production, and nuclear factor-kappaB (NF-kappaB) phosphorylation of CD4<sup>+</sup> and CD8<sup>+</sup> T cells were detected using flow cytometry...
July 6, 2018: Stem Cells and Development
Jennifer J P Collins, Marissa A Lithopoulos, Claudia C Dos Santos, Nahla Issa, Marius A Möbius, Caryn Ito, Shumei Zhong, Arul Vadivel, Bernard Thébaud
Bronchopulmonary dysplasia (BPD), the most common complication of extreme preterm birth, can be caused by oxygen-related lung injury and is characterized by impaired alveolar and vascular development. Mesenchymal stromal cells (MSCs) have lung protective effects. Conversely, BPD is associated with increased MSCs in tracheal aspirates. We hypothesized that endogenous lung (L-)MSCs are perturbed in a well-established oxygen-induced rat model mimicking BPD features. Rat pups were exposed to 21% or 95% oxygen from birth to postnatal day 10...
June 29, 2018: Stem Cells and Development
Tingting Gao, Xin Zhao, Chenchen Liu, Binbin Shao, Xi Zhang, Kai Li, Jinyang Cai, Su Wang, Xiaoyan Huang
Spermatogonial stem cell (SSC) self-renewal is an indispensable part of spermatogenesis. Angiotensin I-converting enzyme (ACE) is a zinc dipeptidyl carboxypeptidase that plays a critical role in the regulation of the renin-angiotensin system. In this study, we used reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis to confirm that somatic ACE (sACE), but not testicular ACE (tACE), is expressed in mouse testis before postpartum day 7 and in cultured SSCs. Our results revealed that sACE is located on the membrane of SSCs...
June 29, 2018: Stem Cells and Development
B Elisabeth Rink, Teresa Beyer, Hilari M French, Elaine Watson, Christine Aurich, F Xavier Donadeu
Because of their distinct differentiation, immunomodulatory, and migratory capacities, endometrial mesenchymal stromal cells (MSCs) may provide an optimum source of therapeutic cells not only in relation to the uterus but also for regeneration of other tissues. This study reports the fate of endometrial MSCs following intrauterine application in mares. Stromal cell fractions were isolated from endometrial biopsies taken from seven reproductively healthy mares, expanded, and fluorescence labeled in culture. Phosphate-buffered saline (PBS) or MSCs (15 × 106 ) were autologously infused into each uterine horn during early diestrus and subsequently tracked by fluorescence microscopy and flow cytometry of endometrial biopsies and blood samples taken periodically after infusion...
June 29, 2018: Stem Cells and Development
Masaru Abiko, Takafumi Mitsuhara, Takahito Okazaki, Takeshi Imura, Kei Nakagawa, Takashi Otsuka, Jumpei Oshita, Masaaki Takeda, Yumi Kawahara, Louis Yuge, Kaoru Kurisu
The functional disorders caused by central nervous system (CNS) diseases, such as ischemic stroke, are clinically incurable and current treatments have limited effects. Previous studies suggested that cell-based therapy using mesenchymal stem cells (MSCs) exerts therapeutic effects for ischemic stroke. In addition, the characteristics of MSCs may depend on their sources. Among the derived tissues of MSCs, we have focused on cranial bones originating from the neural crest. We previously demonstrated that the neurogenic potential of human cranial bone-derived MSCs (cMSCs) was higher than that of human iliac bone-derived MSCs...
June 29, 2018: Stem Cells and Development
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