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Publisher: Smart Science and Technology LLC   (Total: 21 journals)   [Sort by number of followers]

Showing 1 - 21 of 21 Journals sorted alphabetically
Abdomen     Open Access  
Cancer Cell & Microenvironment     Open Access   (Followers: 8)
Cardiovascular Regenerative Medicine     Open Access  
Evidence-based Medicine & Public Health     Open Access   (Followers: 6)
Immunoendocrinology     Open Access   (Followers: 1)
Inflammation and Cell Signaling     Open Access   (Followers: 2)
Itch & Pain     Open Access   (Followers: 2)
J. of Advanced Nutrition and Human Metabolism     Open Access   (Followers: 14)
Macrophage     Open Access  
Molecular & Cellular Epilepsy     Open Access   (Followers: 2)
Musculoskeletal Regeneration     Open Access   (Followers: 2)
Neurotransmitter     Open Access  
Precision Medicine     Open Access   (Followers: 1)
Receptors & Clinical Investigation     Open Access   (Followers: 1)
RNA & Disease     Open Access   (Followers: 1)
Science Proceedings     Open Access   (Followers: 1)
Stem Cell and Translational Investigation     Open Access   (Followers: 2)
Stem Cell Epigenetics     Open Access   (Followers: 3)
Telomere and Telomerase     Open Access  
Therapeutic Targets for Neurological Diseases     Open Access   (Followers: 1)
Uterus & Ovary     Open Access  
Journal Cover Stem Cell and Translational Investigation
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   ISSN (Online) 2377-2557
   Published by Smart Science and Technology LLC Homepage  [21 journals]
  • Transgenic silkworms producing sericin cocoons applicable for tissue

    • Authors: Eiji Kotnai, Hajime Mori
      Abstract: Specific gene functions have been successfully suppressed by gene silencing or editing in many organisms. However, genetic manipulation to suppress the function of a target tissue has not been achieved using genes such as cytotoxin family members. We established transgenic silkworms with posterior silk glands (PSGs) that express the enzymatic domain of the cytotoxin pierisin-1A (P1A), a recently identified cytotoxic protein from the cabbage butterfly Pieris rapae, which has a relatively lower DNA ADP-ribosylating activity among the pierisin family. Larvae with the modified PSGs produced sericin cocoons with potential utility in tissue engineering. Our observations of an embryonic stem (ES) cell proliferation on fabricated sericin hydrogels demonstrated that such gels can act as a scaffolds to support cell growth and also mimic extracellular matrices to provide cell growth factors. In this highlight paper, we describe a new approach through targeted P1A expression, which could be applicable to the development of biologically-useful model organisms with tissue-specific dysfunction.
      PubDate: 2017-09-11
      DOI: 10.14800/scti.1593
      Issue No: Vol. 4 (2017)
  • Research Highlight: Bicistronic 2A-peptide-based co-expression reporter
           knock-in strategy by CRISPR/Cas9 system: application to the labeling of
           specific cell lineages and gene expression monitoring.

    • Authors: Kohei Homma
      Abstract: Fluorescent cell labeling is used to identify the specific cell lineages in a tissue or a whole organism. Transgenic organisms with fluorescent reporter genes have been created to visualize specific cell lineages and to investigate cell specific morphologies, motilities, gene expressions, neural activities, intracellular signaling, etc. However, in human cells, transgenes are often silenced during cell differentiation, and so knock-in technology was adopted to label the specific human cell lineages, although the establishment of knock-in human pluripotent stem cells (hPSCs) required considerable efforts. Genome editing technology paved the way to more efficient and useful knock-in methods. Also, we applied a bicistronic 2A-peptide-based co-expression (B2AC) system to the knock-in strategy for the fluorescent cell labeling. By using these technologies, knock-in hPSC lines were established, and the expression of Crx, a specific photoreceptor marker, was revealed during three-dimensional retinal organoid culture. The Crx expression and fluorescent intensity in the cells were positively correlated, suggesting that the B2AC reporter system functioned during human retinal development. The immunohistochemistry of Crx and the maturation of fluorescent reporter cells after long-term differentiation culture indicated that knock-in of the reporter gene did not affect the function of the target Crx gene. B2AC reporter cells successfully represented Crx upregulation by DAPT, a Notch signal inhibitor, during retinal differentiation from hPSC. These results indicated that the B2AC reporter knock-in system could be used to investigate cell transplantation, developmental mechanisms, disease signaling, drug screening, and intracellular signaling.
      PubDate: 2017-06-07
      DOI: 10.14800/scti.1551
      Issue No: Vol. 4 (2017)
  • Microfabric vessel-based system for efficient 3D culture and rapid
           differentiation of pluripotent stem cells for regenerative medicine

    • Authors: Hiroki Sato, Alimjan Idiris, Tatsuaki Miwa, Hiromichi Kumagai
      Abstract: To facilitate regenerative medicine using pluripotent stem cells, such as ES/iPS cells, a stable supply of cells with uniform quality is essential. Several suspension culture techniques have been developed for the stable supply and mass production of cellular raw material, but unsolved issues still remain. In our previous report, we established a protocol for the easy, large-scale preparation of cell spheroids of uniform size based on the utilization of a special microfabric culture vessel, i.e., an “EZSPHERE.” Additionally, we found that changing the medium composition enables to carry out not only spheroid formation and proliferation, but also differentiation and maturation within the same culture vessel. This culture system can be characterized, unlike existing suspension culture techniques, by the ability to achieve high-density incubation of spheroids, thus enabling the formation of high-purity neural stem cell spheroids in a short time via the physiological activity of endogenous secretory factors. Thus, the establishment of a system for the high-density culture of homogeneous spheroids not only resolved open issues related to large-scale culture for the realization of regenerative medicine, but also provided a unique research tool for gaining new insights in the field of stem cell biology. This system is expected to contribute greatly to advancing translational research related to regenerative medicine.
      PubDate: 2017-05-24
      DOI: 10.14800/scti.1541
      Issue No: Vol. 4 (2017)
  • Chondrogenic differentiation of embryonic stem cells using
           mechanotransductive 3-D PDMS scaffolds

    • Authors: Christina McKee, Donggang Yao, G. Rasul Chaudhry
      Abstract: Embryonic stem cells (ESCs) are an ideal source for cell therapy and regenerative medicine.  ESCs must be differentiated prior to their use for therapeutic applications.  However, homogeneous differentiation of ESCs in vitro has proven to be challenging.  We hypothesized that both biological and mechanical cues contribute to the specific differentiation of ESCs in vivo. This was tested by mimicking the in vivo microenvironment to differentiate ESCs into chondrogenic lineage using highly elastic polydimethylsiloxane (PDMS) scaffolds and the application of mechanical compression in vitro. ESCs seeded in PDMS scaffolds subjected to static compressive stress resulted in significant upregulation of genes, Sox9, Col2, and Acan, involved in early chondrogenic differentiation. However, the compressive stress did not affect expression of the late hypertrophic markers, Runx2, Col10, and Mmp13, signifying induction of ESCs into early chondroprogenitors. Application of mechanical stress increased expression of mechanical signaling genes, Rhoa, Yap, and Taz. The chondroinductive role of Rhoa was confirmed by the inhibition of RhoA signaling by CCG-1423, which resulted in decreased transcriptional and translational expression of chondrogenic markers. Based on these findings, we proposed a strategy for compression induced chondrogenic differentiation in mechanotransductive 3-D PDMS scaffolds.
      PubDate: 2017-04-17
      DOI: 10.14800/scti.1536
      Issue No: Vol. 4 (2017)
  • A Basis for Comparison: Sensitive Authentication of Stem Cell Derived RPE
           Using Physiological Responses of Intact RPE Monolayers

    • Authors: Kiyoharu Joshua Miyagishima, Qin Wan, Sheldon S. Miller, Kapil Bharti
      Abstract: The retinal pigment epithelium (RPE) is a monolayer of highly specialized cells that help maintain the chemical composition of its surrounding subretinal and choroidal extracellular spaces.  Retinal cells (photoreceptors in particular), RPE, and choroidal endothelial cells together help ensure a homeostatically stable metabolic environment with exquisitely sensitive functional responses to light. Aging and disease of the RPE impairs its supportive functions contributing to the progressive loss of photoreceptors and vision.  The prevalence of RPE associated retinal degenerations has prompted researchers to develop new therapies aimed at replacing the affected RPE with induced pluripotent stem cell (iPSC) or embryonic stem cell (ESC) derived RPE.  Despite recent attempts to characterize stem cell derived RPE and to truly authenticate RPE for clinical applications, there remains a significant unmet need to explore the heterogeneity resulting from donor to donor variation as well as the variations inherent in the current processes of cell manufacture.   Additionally, it remains unknown whether the starting cell type influences the resulting RPE phenotype following reprogramming and differentiation.  To address these questions, we performed a comprehensive evaluation (genomic, structural, and functional) of 15 iPSC derived RPE originating from different donors and tissues and compiled a reference data set for the authentication of iPSC-derived RPE and RPE derived from other stem cell sources.
      PubDate: 2017-01-24
      DOI: 10.14800/scti.1497
      Issue No: Vol. 4 (2017)
  • The Cultural Authority of Stem Cell Researchers

    • Authors: Timothy L. O'Brien
      Abstract: Increasing public support for stem cell researchers may increase their influence over science policy decisions and lead to more favorable policies regarding stem cell research. Yet, until recently there was little scholarship on public opinion about the roles stem cell researchers should play in crafting science policy. A national survey of US adults found that Americans are generally supportive of stem cell researchers as policy advisers but that support is uneven throughout the public. Specifically, attitudes about stem cell researchers as policy advisers depend on gender, political beliefs, age and religiosity. Surprisingly, familiarity with science has a negative effect on attitudes about stem cell researchers as policy makers. This suggests that rather than simply “teaching” the public more scientific facts, science outreach and communication may be most effective when it is narrowly tailored to the match the interests of specific social groups. It also suggests that attitudes about stem cell researchers are rooted in deeply-held cultural dispositions and that widespread changes in public opinion are likely to occur slowly.
      PubDate: 2016-10-03
      Issue No: Vol. 3 (2016)
  • Transplantation of hypoxia-inducible factor-1α gene modified neural stem
           cells increases cell survival and angiogenesis after cerebral ischemia

    • Authors: Hua Ye, Ming-rui Chen, Wan-fu Wu
      Abstract: Previous studies have indicated the beneficial effects of transplanted neural stem cells (NSCs) on cerebral ischemia. Hypoxia-inducible factor-1α (HIF-1α) is a master transcription factor of cellular hypoxic gene expression, and its signal pathway might be the primary mechanism through which hypoxia promotes the growth of NSCs. To test the hypothesis that HIF-1α contributes to the therapeutic effect of NSCs transplantation in cerebral ischemia, we compared the efficacy of transplanting PBS, NSCs infected with recombinant adenovirus, HIF-1α gene and NSCs infected with a recombinant adenovirus vector with HIF-1α gene (HIF-1α-NSCs). A transient middle cerebral artery occlusion (tMCAO) was used in this study. PBS, HIF-1α gene, NSCs and HIF-1α-NSCs were respectively injected into cortical peri-infarction of the rat brain at 24 h after MCAO. Neurological deficits were assessed using the modified neurological severity score (NSS). Immunohistochemistry for BrdU, VEGF, Von Willebrand Factor and Nissl staining were performed. Compared with other groups HIF-1α-NSCs showed better behavioral recovery at 7, 14, 21and 28 days, and lesser degree of brain atrophy in cortex and hemisphere. More BrdU-positive cells in HIF-1α-NSCs group than that in NSCs group. Expression of VEGF and Von Willebrand Factor are both higher in HIF-1α-NSCs than those in HIF-1α or in NSCs group. Thus, we concluded that during the early period after transplantation HIF-1α infected NSCs expressed gene products,which reduce brain injury by improving the survival of NSCs and protecting the vascular system.
      PubDate: 2016-08-28
      Issue No: Vol. 3 (2016)
  • Gadonanotube materials as new intracellular MRI contrast agents for stem
           cell labeling

    • Authors: Mayra Hernández-Rivera, Lon J. Wilson
      Abstract: Stem cells possess great potential for different medical applications and every year more investigators join this field of study. As interest in stem cells has increased, it has become essential to track the cells in vivo in order to study their biodistribution and possible tissue accumulation. Here, we review the use of two new carbon nanotube-based contrast agents (CAs) for magnetic resonance imaging (MRI) called Gadonanotube (GNT) materials, which contain Gd3+-ion clusters or Gd3+ chelates within the sidewall cavities of 20-80 nm long carbon nanotube (CNT) capsules. These ultra-high-performance T1-weighted CAs have been use to label a number of mammalian cells, including porcine bone marrow-derived mesenchymal stem cells without any observed cytotoxicity. Furthermore, various in vitro and in vivo preclinical studies have demonstrated the safety and potential of these new CNT-based materials as intracellular CA labels for stem cell tracking by MRI.   
      PubDate: 2016-08-15
      Issue No: Vol. 3 (2016)
  • Ream content a stem cell source for bone defects

    • Authors: Shirin Toosi, Elham Vahednia, Javad Behravan
      Abstract: Bone grafts are normally used for the treatment of bone defects and non-union fractures, and the most common donor site is the iliac crest. The reamer-irrigator-aspirator (RIA) is an innovative technology to obtain osseous particles during intramedullary reaming in femur fractures. Discarded RIA can provide abundant native bone marrow mesenchymal stem cells (BM-MSCs) compared to the iliac crest. Autograft obtained from the use of RIA shows osteogenic potential at least equal to the iliac crest autograft with less donor site morbidity. The disadvantages of using the iliac crest including small volume, invasive harvesting, pain for the patient, makes RIA-harvested autograft bone preferable because it has good properties and is amenable for use as a sole alternative to the iliac crest graft or as a graft expander in conjunction with autologous iliac crest bone marrow aspirate.
      PubDate: 2016-08-08
      Issue No: Vol. 3 (2016)
  • The Spector of Plutonium in Modern Warfare

    • Authors: Asaf Durakovic
      Abstract: The current global reality of re-emerging of the Cold War, migration of the large segments of the global population, depletion of natural resources, and the ever-increasing need for alternate energy presents existential challenges to geopolitical unresolved crisis, and ultimately, stability of the biosphere. While the strategic nuclear confrontation is an unlikely scenario because of its irreversible consequences, tactical warfare is a realistic probability of the outcomes of regional and geopolitical differences around the globe. The fragile and limited scope of the stratosphere, including the airspace and waters, provides ever-decreasing probabilities of expansion, limited options for sustainable life, and increasing risk to the survival of the environment. The industrial pollution is enhanced by the nuclear age radioactive environment, which is irreversible in light of man-made insults to the biosphere by the nuclear-era civilian and military release of man-made imbalance. Non-proliferation nuclear treaties, to which not all countries are signatories, do not provide a prospect of security for mankind in the current polarized geopolitical realities, enhanced by clandestine use of nuclear-era destructive powers and by settling regional differences in the confrontational rather than compromising manor.Current realities of the instabilities of the Middle and Far East, large segments of Euro-Asia, shifting of the military priorities, and unceasing production of the nuclear arsenals appear a challenge not only to the well-being, but to sustainable homeostasis. Radiation dispersal devices, nuclear terrorism, renewable energy challenges, chemical and radioactive pollution, melting of the polar caps, and global warming present existential challenges to this fragile segment of the galaxy. The advent of transuranic elements, exemplified by plutonium, adds a recent relatively new dimension to the challenges facing the biosphere. This article attempts to objectively assess the role of radioactive pollution by actinides in the current global reality.
      PubDate: 2016-06-29
      Issue No: Vol. 3 (2016)
  • Stem cells and Aging

    • Authors: Michael A Singer
      Abstract: The prevailing view of the aging process is that it reflects the integrated sequelae of accumulated random biological damage. These sequelae have been referred to as the hallmarks of aging and one of these hallmarks is the age-related decline in somatic stem cell functions; termed stem cell exhaustion. This stem cell exhaustion construct implies that stem cell aging across different tissues should have a number of similar characteristics. However, such is not the case. The characteristics of aging for stem cell populations in a variety of tissues, (hair follicle, skeletal muscle, hematopoietic tissue, skin, intestine and testes), display many distinctive tissue specific features. This observation implies that stem cell exhaustion is not a generic process consequent to the accumulation of random biological damage but rather represents the manifestation of tissue specific evolved programs.
      PubDate: 2016-05-09
      Issue No: Vol. 3 (2016)
  • Cord Blood: Spotlight on the Processing Step

    • Authors: Nobuhiko Sato, Cornelia Fricke
      Abstract: Cord blood (CB) can be stored processed or un-processed. The advantage of applying a processing step to the cord blood units (CBUs) for cord blood banks (CBBs) is that the volume can be reduced by depletion of plasma and sometimes also by reduction of red blood cell (RBC) number. This decreases the associated costs for storage. Another advantage is the reduction of the quantity of cryopreservation solution in the final product. As the RBCs tend to burst during the freezing and thawing step the decrease in RBC numbers reduces the possibly harmful cellular debris and free hemoglobin released by burst RBCs into the CBUs. However processing can potentially cause also a loss of the wanted cells, like the stem cell compartment or cause stress to these cells. Thus, the optimal processing system reduces volume and RBCs while at the same time leaving the wanted cells like the stem cell compartment with its hematopoietic as well as non-hematopoietic stem cells unaffected. Hematopoietic stem cells are mainly used as a source for transplants to reconstitute the blood forming cells while non-hematopoietic stem cells can support the hematopoietic stem cells in the transplant setting but are potentially useful also for other regenerative medicine or immune modulatory purposes. Many CBBs today use a processing step instead of storing the CB un-processed just by the addition of cryopreservation solution. Different processing systems exist which often employ a centrifugation step for processing of the CBUs. In addition, we described recently a manual system, CellEffic CB, which employs a filtration step eliminating the need for centrifugation and thus any machines and its associated costs. We will highlight here recent development in the cord blood industry and how the new filtration system can contribute to this industry.
      PubDate: 2016-05-09
      Issue No: Vol. 3 (2016)
  • Exploiting human iPS cell-derived cardiovascular cell populations toward
           cardiac regenerative therapy

    • Authors: Hidetoshi Masumoto, Jun Yamashita
      Abstract: To achieve induced pluripotent stem cell (iPSC)-based cardiac regenerative therapy, it is indispensable to establish a method to efficiently induce cardiovascular cell populations from human iPSCs (hiPSCs). We have previously reported a novel serum-free high-density monolayer culture method to induce cardiomyocytes (CMs) from hiPSCs using a stage-specific sequential treatment with TGFβ superfamily molecules (Activin A and BMP4) and a canonical Wnt antagonist, Dkk1. We also succeeded in purifying the differentiated CMs by cell sorting, immunologically labelling the vascular cell adhesion molecule-1 (VCAM-1), a CM-specific cell surface marker which was determined by cell surface marker screening. To induce vascular cells along with CMs, we modified the CM induction method using vascular endothelial cell growth factor on mesoderm-staged cells, which led to simultaneous induction of CMs and vascular cells. We reassembled the cardiovascular cell populations to form a cell sheet which showed a potential for cardiac functional recovery in a rodent myocardial infarction model. These cell differentiation toward cardiovascular cell populations from hiPSCs and bioengineered transplantation methods, could potentially promote hiPSC-based cardiac regenerative therapy in the future.
      PubDate: 2016-03-22
      Issue No: Vol. 3 (2016)
  • The role of the cancer stem cell marker USP22 in tumors

    • Authors: Qi Guangying, Mi Sisi, Jin Shengjian, Shao Wenhuan, Liu Jing, Liu Tian, Zeng Sien, Lu Huiling
      Abstract: Ubiquitin specific peptidase 22 (USP22) is one of the 11 known death-from-cancer signature genes. USP22 is also considered a cancer stem cell marker and is highly expressed in a variety of tumor types. USP22 alters the expression of tumor-associated genes (e.g., proto-oncogenes and tumor suppressor genes) and promotes tumor cell proliferation, invasion and metastasis via the modification of cell cycle activity and the activation of a variety of signaling pathways. In patients with tumors, USP22 expression is related to lymphatic metastasis, clinical stage of tumors, survival rate and a number of other factors. In addition, USP22 is considered an indicator of a poor prognosis and thus may be used to evaluate the prognosis of patients with tumors. As a potential cancer stem cell marker, USP22 may serve as a novel target for tumor therapies. Finally, USP22 also plays an important role in tumor development and progression.
      PubDate: 2016-03-22
      Issue No: Vol. 3 (2016)
  • A System for the Surveillance of Stem Cell Fate and Function

    • Authors: Graham G Walmsley, Michael S Hu, H. Peter Lorenz, Michael T Longaker
      Abstract: Cell based therapies represent a promising area of research in regenerative medicine. However, the mechanism by which transplanted cells contribute to bone healing remains unclear. The authors utilized a transgenic mouse strain expressing both the topaz variant of green fluorescent protein under the control of the collagen type I alpha 1 promoter/enhancer sequence (Col1a1GFP) and membrane-bound tomato red constitutively in all cells types (R26mTmG) to decipher how both transplanted and endogenous cells mediate bone healing (1). Calvarial healing was assessed using both parietal and frontal defects and showed that frontal osteoblasts express Col1a1 to a significantly greater degree than parietal osteoblasts. Col1a1GFP; R26mTmG mice were also used to observe the behavior of adipose-derived stromal cells (ASCs), bone marrow-derived mesenchymal stem cells (BM-MSCs), and osteoblasts following transplantation into critical-sized calvarial defects. ASCs significantly increased the rate of bone healing and exhibited both increased survival and Col1a1 expression when compared to BM-MSCs and osteoblasts. These results support the Col1a1GFP; R26mTmG system as a promising technology for the evaluation of stem cell populations in cell-based therapeutics for the purposes of bone healing.
      PubDate: 2016-02-29
      Issue No: Vol. 3 (2016)
  • A strategy for culturing human pluripotent stem cells for translational

    • Authors: Ji-Hye Jung, Byung Soo Kim
      Abstract: The tremendous potential of human pluripotent stem cells (hPSCs) in regenerative medicine has garnered the focus of the scientific community worldwide. However, many limitations need to be addressed before we can use the knowledge for clinical applications. We have had a longstanding interest in establishing a safe, clinical-grade environment for culturing hPSCs. We observed that human placenta-derived (chorionic villi) cells could support and maintain hPSC characteristics without the exogenous supplementation of growth factors. We developed a conditioned medium from human placenta-derived feeder cells. This medium could support hPSC growth on a 0.1% gelatin-coated dish that is commonly used for culturing human cells. Thereafter, we identified candidates affecting the pluripotency of hPSCs through CXCR2 ligands in the absence of bFGF. Our previous study was the first to describe the use of a unique feeder-free humanized culture system to support hPSCs on a gelatin substratum regardless of the presence bFGF. Clearly, the human placenta can be used to not only circumvent many limitations but also is an excellent material for translational research.
      PubDate: 2016-01-12
      Issue No: Vol. 3 (2016)
  • Modeling cocaine-induced alterations in organization and patterning of
           neocortical development using human pluripotent stem cells

    • Authors: Chun-Ting Lee, Abigail Kindberg, William Freed, Tsung-Ping Su
      Abstract: Disorders of human neocortical development are particularly difficult to study by using animal models because of the marked complexity and unique features of the human cerebral cortex. Developmental effects of cocaine, as well as other drugs and toxins, are particularly challenging to study due to complicating factors such as variations in genetic background, time of exposure, and exposure to multiple substances. Studies aimed at elucidating the effects of cocaine on fetal brain development have used rodent cell lines, primary human cells, and rat models to show that cocaine metabolism by cytochrome P450 results in oxidative ER stress and subsequent impairment of neural progenitor cell proliferation. Recently, in vitro models of neocortical development have been generated by using pluripotent stem cells.  One such model, utilizing human pluripotent stem cells, reproduced the formation of neocortical glutamatergic and GABAergic neurons on radial glial scaffolding structure in a temporally sensitive manner mimicking human in vivo neocortical development. Cocaine exposure resulted in the accumulation of reactive oxygen species (ROS), premature neuronal differentiation, accelerated generation of deep-layer and upper-layer glutamatergic projection neurons, and increased formation of GABAergic interneurons. Each of these changes was inhibited by the cytochrome P450 inhibitor cimetidine. These studies suggest that, in the developing human cerebral cortex, cocaine metabolism through cytochrome P450-dependent ROS generation leads to premature neuronal differentiation of neocortical progenitors and impaired neocortical patterning.
      PubDate: 2015-02-13
      Issue No: Vol. 3 (2015)
  • Opposing Biological Functions of Retinoic Acid in Normal Embryonic

    • Authors: Mohsen Sagha, Mohammad Mohammadzadeh-Vardin
      Abstract: Vitamin A and its metabolic derivative, retinoic acid (RA) are essential biomolecules for normal development regulation and regeneration in different organs. Too much and deficiency of vitamin A can be toxic for fetuses lead to birth defects or is associated with many congenital malformations. It has been known that RA alone or in combination with other morphogens promotes the developmental program such as neural differentiation and patterning. Here, we discussed RA role in the neural patterning of the embryonic stem cells and its function in promoting the neural differentiation in neural plate of the developing embryo through attenuating the fibroblast growth factor (FGF) signaling. By using different techniques, we also argued the opposite function of RA in inducing apoptosis in the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) shown by upregulating the caspase expression. Finally, we discussed that some biological parameters including cell density and passage appeared to be involved in this cytotoxicity response
      PubDate: 2015-02-13
      Issue No: Vol. 3 (2015)
  • Leishmaniasis infection in allogeneic stem cell transplantation. An
           “accidental finding”'

    • Authors: Anna Komitopoulou
      Abstract:  Although leishmaniasis is mainly a disease of immunocompetent population, reported cases of the disease related with immunosuppression, have increased during the last decades. The visceral form of the disease is often identified after solid organ transplantation, while limited data of leishmaniasis infection are available after hematopoietic stem cell transplantation.
      PubDate: 2015-02-11
      Issue No: Vol. 3 (2015)
  • The characterization of cardiac stem cells obtained from patients who have
           received left ventriculoplasty.

    • Authors: Emiko Hayashi, Yasunori Cho, Masaki Inoue, Tsutomu Murakami, Toru Hosoda
      Abstract: The recent clinical application of c-kit-positive resident cardiac stem cells (CSCs) for severe heart failure patients revealed their remarkable and long lasting beneficial effects. Ultimately aiming at a combined therapy of left ventriculoplasty and autologous CSC transplantation, we have successfully isolated and cultivated endogenous stem cells from the right atrium and the infarcted left ventricle, respectively, of all subjects in the target population. Three independent parameters, population doubling time, BrdU incorporation, and colony forming ability, each of which indicates the growth property of cultured CSCs, correlated well in every sample. Overall, CSCs derived from both origins possessed a great proliferative potential with a non-significant superiority in the right atrial CSCs. This brief report provides a fundamental basis for regenerative therapy as a potential novel management of ischemic cardiomyopathy, following the ventriculoplasty.
      PubDate: 2015-01-28
      Issue No: Vol. 3 (2015)
  • Flavonoid coated Titanium surfaces for Bioactive Bone implants

    • Authors: Alba Córdoba, María Satué, Manuel Gómez-Florit, Marta Monjo, Joana Maria Ramis Morey
      Abstract: Flavonoids are small polyphenolic molecules, ubiquitously found in nature, with antioxidant, anti-inflammatory and antibacterial properties. Recently, we presented a bioactive surface based on the covalent grafting of flavonoids taxifolin and quercitrin on titanium substrates. The flavonoid-modified surfaces exhibited interesting biological effects in vitro with two human cell types: they stimulated the differentiation of mesenchymal stem cells from umbilical cord (hUC-MSCs) to osteoblasts, and showed anti-inflammatory and anti-fibrotic potential on gingival fibroblasts (HGF). Hence, these bioactive surfaces could readily have a clinical application in the development of advanced dental implants. Flavonoid compounds are being studied for several therapeutic applications –cancer, cardiovascular, liver, neurodegenerative diseases...-. Therefore, flavonoid-modified biomaterials could be used in numerous biomedical applications.
      PubDate: 2015-01-28
      Issue No: Vol. 3 (2015)
  • New immunosuppressive strategies for transplantation based on pluripotent
           stem cell (PSC)-derived immunoregulatory cells

    • Authors: Ken-ichiro Seino, Haruka Wada, Muhammad Baghdadi
      Abstract: Pluripotent stem cells (PSCs) such as embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) have the potential to give rise to cells from all three germ layers that can be utilized as new reliable sources in transplantation medicine. However, when allogeneic PSCs are used for transplant generation, an effective immunosuppressive strategy is required to protect transplants from rejection induced by immune responses of recipient to donor alloantigen after transplantation. Cell-based immunosuppressive strategies offer effective, safe and specific methods to inhibit recipient’s immune response against donor transplant and help to avoid side effects accompanied with conventional immunosuppressant drugs. In this context, we hypothesized that allogeneic PSCs-derived transplants can be protected from immune rejection if accompanied with adoptive transfer of immunosuppressive cells generated from the same PSCs. Indeed, we have developed several differentiation protocols to generate immunosuppressive cells such as regulatory T cells (Tregs) or macrophages from PSCs, which showed promising results to prolong same PSCs-derived graft survival. In this review, we introduce new findings related to PSCs-based cellular immunosuppressive therapy and its applications in several transplantation models.
      PubDate: 2015-01-28
      Issue No: Vol. 3 (2015)
  • Efficient generation of hepatocyte-like cells from rat bone marrow
           mesenchymal stem cells in vitro

    • Authors: jiehua xu, Jie Qin, Dan Li, Ting Jiang, Hong Shan
      Abstract: Recent studies indicated that stem-cell–derived hepatocyte-like cells are superior to stem cells in therapy for liver failure. Our aim is to present a modified one-step protocol for high-efficiency in vitro generation of hepatocyte-like cells from rat bone marrow mesenchymal stem cells (rBMSCs). rBMSCs were cultured under optimal differentiation conditions. Hepatic differentiation was evaluated by light microscopy (for morphological analysis), reverse-transcription polymerase chain reaction (for expression of hepatocyte-specific genes), and immunocytochemical and immunofluorescence analyses of hepatic proteins, such as alpha-fetoprotein and albumin. Functional assays comprised periodic acid-Schiff staining, supernatant urea assay, and albumin radioimmunoassay. The results show that differentiated cells exhibited characteristic hepatocyte morphology, expressed hepatocyte-related genes (as shown by reverse-transcription polymerase chain reaction), and displayed antibody-detectable expressions of alpha-fetoprotein (100% at day 8) and albumin (>70% at 2 weeks). Most differentiated hepatocyte-like cells showed evidence of glycogen synthesis and storage, as shown by periodic acid-Schiff staining. Albumin and urea were detected in supernatants. Our one-step protocol induced the efficient differentiation of rBMSCs into functional hepatocyte-like cells in a two-dimensional in vitro model and may be useful for cell transplantation therapy for liver failure.
      PubDate: 2015-01-03
      Issue No: Vol. 3 (2015)
  • Bone marrow-derived stem cells differentiate into retinal pigment
           epithelium-like cells in vitro but are not able to repair retinal
           degeneration in vivo

    • Authors: Stéphanie Lecaudé, Ute E.K. Wolf-Schnurrbusch, Hannan Abdullahi, Volker Enzmann
      First page: 10
      Abstract: The bone marrow (BM) is home to different stem/progenitor populations, including tissue-committed stem cells. In this context, we have cocultured BM-derived stem cells (BMSC) in order to investigate their differentiation capacity towards the retinal pigment epithelial (RPE) lineage in vitro. Furthermore, pre-differentiated BMSC were transplanted into the pharmacologically damaged subretinal space to determine their rescue ability in vivo. BM was harvested from the tibias and femurs of adult GFP+ C57BL/6 mice. Differentiated hematopoietic cells were removed by lineage depletion, and CD45- BMSCs were separated by magnetic activated cell sorting (MACS). To induce differentiation, the cells were then cocultured with murine RPE for 10 days, and retinal markers were assessed using immunohistochemistry (IHC). To induce retinal degeneration, mice were treated with sodium iodate (NaIO3). Seven days later, approx. 60,000 pre-differentiated GFP+ BMSC, sorted by FACS, were transplanted subretinally. Optical coherence tomography (OCT) was used to follow the transplants and to quantify the retinal thickness over time. Visual acuity was measured concurrently using the optokinetic reflex (OKR). Finally, IHC was performed to investigate the expression of retina-specific markers in the transplants. CD45- BMSC adopted an RPE-like elongated morphology and showed expression of the RPE markers RPE65 and bestrophin after coculture. After transplantation of CD45- BMSC, visual acuity increased in individual animals compared to the contralateral control eye, but did not reach baseline levels. Additionally, no significant increase in retinal thickness in the transplanted eye was found. However, the cells were detectable in the subretinal space for up to 28 days and expressed the RPE markers RPE65 and bestrophin. In summary, the BMSC differentiated into RPE-like cells but were not able to restore visual function or rescue retinal morphology after subretinal transplantation.
      PubDate: 2015-10-15
      Issue No: Vol. 2, No. 2 (2015)
  • Ovarian Germline Stem Cells (OGSCs) and the Hippo Signaling Pathway
           Association with Physiological and Pathological Ovarian Aging in Mice

    • Authors: Jia Li
      First page: 10
      PubDate: 2015-09-22
      Issue No: Vol. 2, No. 2 (2015)
  • Nutraceuticals and cardiovascular risk: potential role of EPCs modulation

    • Authors: Rossella Russo, Danela Lucchesi, Vincenzo Longo, Morena Gabriele, Giuseppe Penno, Laura Pucci
      First page: 10
      Abstract: According to WHO cardiovascular diseases (CVDs) are the first cause of death in the world: more people die annually from CVDs than from any other cause. Vascular endothelium plays a pivotal role in the onset and the progression of these pathologies and cardiovascular risk factors are frequently associated to the levels of endothelial progenitor cells (EPCs), bone marrow-derived circulating progenitors for the endothelial lineage.Since EPCs not only preserve vascular endothelium homeostasis, but directly participate to re-endothelization and neovascularization, these cells represent an emerging actor in vascular competence and thus a cell model of great interest.An unhealthy diet is one of the main cardiovascular risk factor; there is indeed a great interest in the potential  protective effects of "nutraceuticals,", food-derived compounds that exert beneficial effects on human and animal health. The characterization of the endothelial effects of different nutraceuticals may provide fresh insights into their potential role in CVDs prevention. Several studies have already showed the protective effects of natural antioxidants on EPCs levels and functionality; some examples are resveratrol, catechin and folic acid.Fermentation has recently shown interesting roles in cardiovascular prevention since this process created a new class of food, rich in bioactive compounds, the fermented food.Consumption of fermented legumes and cereals, but also fermented beverages (such as beer and wine) was found to protect endothelial function through lipid-lowering, anti-inflammatory and antioxidative mechanisms. Little is known about the effects of fermentation-derived nutraceuticals on EPCs and given the important role of this cardiovascular biomarker, further analysis in this field can improve CVDs prevention and treatment.
      PubDate: 2015-09-22
      Issue No: Vol. 2, No. 2 (2015)
  • An emerging interplay between altered human lipid metabolism,
           lipodystrophy and aging

    • Authors: Arantza Infante, Clara I. Rodríguez
      First page: 10
      Abstract: LMNA-Lipodystrophies are a group of heterogeneous syndromes, with either genetic or acquired origin, characterized by the accumulation of prelamin A, an inmature form of the protein lamin A, one of the major components of the nuclear lamina. Several molecular studies suggest lamin A is involved in adipocyte development, the disruption of which leads to compromised regulation of adipogenesis, adipocyte lipid droplet formation and maintenance, and subsequent secondary dysfunctions in fat metabolism. Moreover, these diseases clinically present with generalized or partial fat atrophy connected with metabolic complications, such as insulin-resistant diabetes and dyslipidemia, in addition to age associated manifestations. There is a real need to increase our understanding regarding these syndromes because of their import in human health and the lack of knowledge of their etiopathology. To gain deeper insights into these metabolic diseases, we have taken advantage of a previously generated “disease in a dish” model of human LMNA-lipodystrophy based on the pathological accumulation of the precursor prelamin A in stem cell derived adipocytes. This experimental model recapitulates phenotypes observed in lipodystrophic patient’s samples and animal models, and it has been critical in elucidating new insights into the molecular mechanisms governing this set of disorders.Recently, we have identified alterations in fundamental processes of lipid homeostasis such as lipolysis, as well as mitochondrial and endoplasmic reticulum functions, similar to what can be observed in some metabolic and aging phenotypes. Additionally, the lipidomic profile of this lipodystrophic experimental model displayed a lipid metabolic signature similar to aging systems, providing new information concerning metabolic pathways affected during the aging process. By clarifying the fundamental mechanisms governing these aging associated diseases, future novel interventions could be developed that will at least delay the appearance of aging phenotypes and thereby increase the healthspan or disease-free time of an individual.
      PubDate: 2015-09-07
      Issue No: Vol. 2, No. 2 (2015)
  • RNA editing enzyme ADAR1 in human iPS cells

    • Authors: Shota Katayama
      First page: 10
      PubDate: 2015-08-06
      Issue No: Vol. 2, No. 2 (2015)
  • Mechanism of Valproic Acid-Induced Hepatotoxicity in Alpers Syndrome Using
           an Induced Pluripotent Stem Cell Model

    • Authors: jingyi guo, zhongfu ying, yi wu, Xingguo Liu
      First page: 10
      Abstract: Valproic acid (VPA) is a widely used antiepileptic drug to treat epilepsy and psychiatric disorders, but potentially causes idiosyncratic liver injury. Alpers-Huttenlocher syndrome (AHS), a neurometabolic disorder caused by mutations in mitochondrial DNA polymerase gamma (POLG), is associated with an increased risk of developing fatal VPA hepatotoxicity. However, the mechanistic link of this clinical mystery remains unknown. Here, we established an induced pluripotent stem cell (iPSC) toxicity model to explore the mechanism behind the high risk of VPA-induced liver injury in AHS. By this model, we demonstrated that AHS iPSCs-hepatocytes are more sensitive to VPA-induced mitochondrial-dependent apoptosis than controls. Furthermore, Superoxide flashes, spontaneous bursts of superoxide generation, caused by opening of the mitochondrial permeability transition pore (mPTP), occur more frequently in AHS iPSCs-hepatocytes, and the mPTP inhibitor, cyclosporine A, is able to rescue VPA-induced apoptotic sensitivity. In addition, carnitine and N-acetylcysteine, which has been used to treat VPA-induced liver injury, also rescue VPA-induced apoptotic sensitivity.
      PubDate: 2015-06-29
      Issue No: Vol. 2, No. 2 (2015)
  • Role of Krüppel-like factor 5 in the maintenance of the stem cell
           niche in the intestinal crypt

    • Authors: Vincent W Yang
      First page: 10
      Abstract: The intestinal epithelium is a tissue that undergoes continuous self-renewal initiated at the bottom of the crypts, which harbor the intestinal stem cell (ISC) pool.  The ISC pool is sub-divided into crypt base columnar (CBC) cells at the crypt bottom and label retention cells (LRC) at position +4 from the crypt bottom.  CBC cells are marked by Leucine-rich repeat-containing G-protein coupled receptor (Lgr5) while LRC cells are identified by several markers including Bmi1, mTert, Hopx, Lrig1, and Sox9.  Krüppel-like factors (KLFs) belong to a family of transcription factors that exert important physiological function in various tissues.  In the intestine, KLF4 is predominantly expressed in the terminally differentiated, non-proliferating cells lining the villus.  Its deletion in the adult mouse intestine results in perturbed homeostasis.  In contrast, KLF5 is expressed in actively proliferating cells of the intestinal crypt, including CBC cells and transit amplifying (TA) cells.  We recently investigated the effect of Klf5 deletion specifically from the Lgr5-expressing CBC cells in adult mouse intestine using an inducible Cre recombinase system.  Shortly (3-5 days) after Cre induction, proliferation of both CBC and TA cells ceased, which was accompanied by an increase in apoptosis in the crypt.  Beginning at two weeks following Cre induction, both Klf5 expression and proliferation re-appeared but without the re-emergence of Lgr5-positive CBC cells, which were eventually depleted by four months following induction. These findings indicate that KLF5 plays an important role in regulating proliferation and survival of CBC stem cells in the intestine.
      PubDate: 2015-05-25
      Issue No: Vol. 2, No. 2 (2015)
  • Cardiac stem cell therapies for congenital heart diseases

    • Authors: Shuta Ishigami, Shunji Sano, Hidemasa Oh
      First page: 10
      Abstract: During the last 2 decades, stem cell therapies with bone marrow mononuclear cells (BMMNCs) or mesenchymal stem cells (MSCs) to treat ischemic heart disease, including in pre-clinical and clinical trials, have demonstrated the ability of stem cells to improve cardiac function, infarct size, and cardiac remodeling in adult patients. In recent years, endogenous cardiac stem cells (CSCs) derived from heart tissue have been identified. CSCs have been shown to have superior regenerative potential over other types of stem cells in terms of cardiovascular-lineage differentiation, paracrine factor secretion, and functional improvement after cell transplantation. Cardiac stem cell therapy to regenerate damaged myocardium after chronic infarction has been reported in the SCIPIO and CADUCEUS trials. In contrast, although recent advances in pediatric cardiology, congenital cardiac surgery, and intensive care management have dramatically changed clinical outcomes, there is an increasing recognition of limited therapeutic improvement in children with severe heart failure. Congenital heart failure is a structural heart disease caused by multiple etiologies related to pressure and volume overload, arrhythmia, and myocardial degradation. Stem cell-based strategies to treat heart failure in adults have been investigated; however, little is known about their safety and efficacy in children and planned clinical studies are quite limited. Only case reports have been published and no large clinical trials have been conducted using any type of stem cells. Recently, the TICAP trial has revealed the safety and feasibility of intracoronary infusion of autologous cardiosphere-derived cells (CDCs) in children with hypoplastic left heart syndrome (HLHS). Although this trial had several limitations that required further evaluation, the results from this study provided a foothold for stem cell-based therapeutic strategies in patients with congenital heart disease. Eventually, a new paradigm of stem cell therapy to treat congenital heart failure has started to form. Many important issues including long-term cell engraftment, the mechanism of stem cell recruitment and differentiation, administration route, and appropriate cell types to deliver in situ remain to be investigated. Here, we review the latest research on stem cell therapies for heart failure and discuss the future perspectives on cell-based regenerative strategies to treat patients with congenital heart diseases.
      PubDate: 2015-05-04
      Issue No: Vol. 2, No. 2 (2015)
  • Cancer Stem Cells in Acute lymphoblastic Leukemia

    • Authors: amir atashi
      First page: 10
      Abstract: Different models were suggested for cancer development. One of them is cancer stem cell model. In this model, Invasion, relapse and resistance to anti-cancer drugs were seen in cancerous cells are related to these cells. Recently, weobserved that some of population in T-Acute lymphoblastic leukemia cell line display cancer stem cell properties. These cells were detected by CD133 marker. In vitro transwell assay showed that CD133+ Jurkat cells were more invasive than CD133- Jurkat cells and also gene expression analysis confirmed CD133+ Jurkat cells expressed MMP9 gene in high levels. After treatment of CD133+ cells with doxorubicin, Annexin-PI staining showed that these cells have high resistance to chemotherapy drug. We demonstrated chemotherapy resistance may be because of up regulation of ABCG2 gene. In addition, CD133+ cells had unrestricted proliferation potential and were able to differentiate to cells with low growth potential (CD133-). Altogether; we demonstrated that CD133 could be as a marker to recognize cancer stem cells in Jurkat cell line.
      PubDate: 2015-04-28
      Issue No: Vol. 2, No. 2 (2015)
  • Adipose-derived stromal/stem cells as a potential source of skin

    • Authors: Toshio Hasegawa, Shigaku Ikeda
      First page: 10
      Abstract: Adipose-derived stromal/stem cells are easily harvested in large quantities with a minimal size of donor site, and have the potential to differentiate into a variety of cell types. Based on the observation that the specific keratinocyte markers p63 and desmoglein 3 are expressed in adipose-derived stromal/stem cells and that their expression is downregulated after the differentiation of these cells into adipocytes, we speculate that adipose-derived stromal/stem cells have the potential to differentiate into epithelial cells. Moreover, adipose-derived stromal/stem cells treated with retinoic acid and bone morphogenetic protein 4, and co-cultured with fibroblasts on type IV collagen have expressed approximately 8 times higher levels of desmoglein 3 and cytokeratin-5 expression. These findings indicated that suitable scaffolds, growth factors, or external environments are needed in clinical use of adipose-derived stromal/stem cells in treating skin diseases. Cultured adipose-derived stromal/stem cell preparations are heterogeneous and consist of different populations of stem and progenitor cells. For a more efficient induction of differentiation, cell sorting would be necessary, by selection for markers specific to the individual subpopulations. Adipose-derived stromal/stem cells play an increasingly important role as a source of transplantable cells in the treatment of several types of diseases including skin diseases. Further preclinical and clinical studies are needed to establish the efficient introduction of adipose-derived stromal/stem cells for the treatment of skin diseases or conditions.
      PubDate: 2015-04-28
      Issue No: Vol. 2, No. 2 (2015)
  • Is CITED2 a general regulator of stem cell functions'

    • Authors: José Bragança, João Miguel Almeida Santos
      First page: 10
      Abstract: In vertebrates, stem cells play a fundamental role in embryogenesis and lifetime homeostasis of adult tissues. The transcriptional regulator Cited2 is essential for many mouse developmental and morphological processes, and mutations in human CITED2 gene have repeatedly been associated with congenital heart defects. An increasing number of studies have now described the importance of Cited2 in self-renewal and cell fate decision of embryonic stem cells (ESC) and some adult stem cells. Interestingly, the loss of stem cell properties due to aging or extensive regeneration of some adult stem cells has been associated with a decrease of Cited2 expression, while an aberrant increase in CITED2 expression might play a critical role in malignant oncologic processes. Here, we review recent advances unravelling the complexity of Cited2 function as a regulator of the maintenance and cell fate decision of ESC and adult stem cells, and present its potential role in pathological conditions by modulating stem cells properties.
      PubDate: 2015-04-13
      Issue No: Vol. 2, No. 2 (2015)
  • Successful Hematopoietic stem cell transplantation (HSCT) from matched
           unrelated donor (MUD) in a pediatric patient using myeloablative regimen
           suffering from MDS: case report from western India.

    • Authors: Irappa Madabhavi, Gaurang Modi, Sandip Shah, Apurva Patel, Swaroop Revannasiddaiah, Asha Anand, Harsha Panchal, Sonia Parikh
      First page: 10
      Abstract: Myelodysplastic syndrome (MDS) is heterogeneous hematopoietic stem cell disorders characterized by ineffective erythropoiesis and dyserythropoiesis. Allogenic HSCT from siblings in our country in pediatric MDS is very well documented. But HSCT from matched unrelated donor (MUD) in paediatric age is still a new concept to implement in our country. We are here presenting the relapse case of MDS (myelodysplastic syndrome) and we had done successful HSCT from MUD in a 14 year old paediatric patient. Myeloablative regimen (fludarabine, busulfan, cyclophosphamide, ATG) was used during HSCT. 100% donor chimerism was found on +day 34 VNTR study. Patient is doing well 1year after HSCT without any complications.
      PubDate: 2015-04-07
      Issue No: Vol. 2, No. 2 (2015)
School of Mathematical and Computer Sciences
Heriot-Watt University
Edinburgh, EH14 4AS, UK
Tel: +00 44 (0)131 4513762
Fax: +00 44 (0)131 4513327
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