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Stem Cells Translational Medicine

Shaun M Kunisaki
Over the past decade, amniotic fluid-derived stem cells have emerged as a novel experimental approach aimed at improving outcomes in children with congenital anomalies, including spina bifida, heart defects, and diaphragmatic hernia. Interest in these cells for the treatment of prenatally diagnosed diseases has arisen based on numerous studies demonstrating the relative ease of harvesting an abundant quantity of amniocytes from a small aliquot of fluid, the unique properties of amniocytes themselves, and the beneficial effects of amniotic fluid-derived stem cells in experimental animal models...
August 7, 2018: Stem Cells Translational Medicine
Narihito Nagoshi, Mohamad Khazaei, Jan-Eric Ahlfors, Christopher S Ahuja, Satoshi Nori, Jian Wang, Shinsuke Shibata, Michael G Fehlings
Cell transplantation therapy utilizing neural precursor cells (NPCs) is a conceptually attractive strategy for traumatic spinal cord injury (SCI) to replace lost cells, remyelinate denuded host axons and promote tissue sparing. However, the number of mature oligodendrocytes that differentiate from typical NPCs remains limited. Herein, we describe a novel approach to bias the differentiation of directly reprogrammed human NPCs (drNPCs) toward a more oligodendrogenic fate (oNPCs) while preserving their tripotency...
August 7, 2018: Stem Cells Translational Medicine
Johnny Lam, Ian H Bellayr, Ross A Marklein, Steven R Bauer, Raj K Puri, Kyung E Sung
Multipotent stromal cells (MSCs) are an attractive cell source for bone and cartilage tissue repair strategies. However, the functional heterogeneity of MSCs derived from different donors and manufacturing conditions has limited clinical translation, emphasizing the need for improved methods to assess MSC chondrogenic capacity. We used functionally relevant morphological profiling to dynamically monitor emergent morphological phenotypes of chondrogenically induced MSC aggregates to identify morphological features indicative of MSC chondrogenesis...
August 7, 2018: Stem Cells Translational Medicine
Rebecca Lim, Atul Malhotra, Jean Tan, Siow Teng Chan, Sinnee Lau, Dandan Zhu, Joanne C Mockler, Euan M Wallace
Bronchopulmonary dysplasia (BPD) is a chronic lung disease that mainly affects premature babies who require ventilator support. The pathogenesis of BPD is complex but includes vascular maldevelopment, alveolarization arrest, and lung inflammation. There is no cure for BPD. Clinical care is limited to supportive respiratory measures. A population of stem-like cells derived from placental membranes, human amnion epithelial cells (hAECs), has shown therapeutic promise in preclinical models of BPD. With a view to future efficacy trials, we undertook a first-in-human clinical trial of hAECs in babies with BPD to assess the safety of these cells...
August 5, 2018: Stem Cells Translational Medicine
Mitchell J George, Karthik Prabhakara, Naama E Toledano-Furman, Yao-Wei Wang, Brijesh S Gill, Charles E Wade, Scott D Olson, Charles S Cox
Clinical cellular therapeutics (CCTs) have shown preliminary efficacy in reducing inflammation after trauma, preserving cardiac function after myocardial infarction, and improving functional recovery after stroke. However, most clinically available cell lines express tissue factor (TF) which stimulates coagulation. We sought to define the degree of procoagulant activity of CCTs as related to TF expression. CCT samples from bone marrow, adipose, amniotic fluid, umbilical cord, multi-potent adult progenitor cell donors, and bone marrow mononuclear cells were tested...
August 1, 2018: Stem Cells Translational Medicine
Timothy E G Krueger, Daniel L J Thorek, Samuel R Denmeade, John T Isaacs, W Nathaniel Brennen
The development of mesenchymal stem cells (MSCs) as cell-based drug delivery vectors for numerous clinical indications, including cancer, has significant promise. However, a considerable challenge for effective translation of these approaches is the limited tumor tropism and broad biodistribution observed using conventional MSCs, which raises concerns for toxicity to nontarget peripheral tissues (i.e., the bad). Consequently, there are a variety of synthetic engineering platforms in active development to improve tumor-selective targeting via increased homing efficiency and/or specificity of drug activation, some of which are already being evaluated clinically (i...
August 1, 2018: Stem Cells Translational Medicine
Martin Teraa, Hendrik Gremmels, Joep G J Wijnand, Marianne C Verhaar
No abstract text is available yet for this article.
August 1, 2018: Stem Cells Translational Medicine
Michael Murias, Samantha Major, Scott Compton, Jessica Buttinger, Jessica M Sun, Joanne Kurtzberg, Geraldine Dawson
This study was a phase I, single-center, and open-label trial of a single intravenous infusion of autologous umbilical cord blood in young children with autism spectrum disorder (ASD). Twenty-five children between the ages of 2 and 6 with a confirmed diagnosis of ASD and a qualified banked autologous umbilical cord blood unit were enrolled. Safety results and clinical outcomes measured at 6 and 12 months post-infusion have been previously published. The purpose of the present analysis was to explore whether measures of electroencephalography (EEG) theta, alpha, and beta power showed evidence of change after treatment and whether baseline EEG characteristics were predictive of clinical improvement...
August 1, 2018: Stem Cells Translational Medicine
Juliana Redondo, Pamela Sarkar, Kevin Kemp, Kate J Heesom, Alastair Wilkins, Neil J Scolding, Claire M Rice
The potential of autologous cell-based therapies including those using multipotent mesenchymal stromal cells (MSCs) is being investigated for multiple sclerosis (MS) and other neurological conditions. However, the phenotype of MSC in neurological diseases has not been fully characterized. We have previously shown that MSC isolated from patients with progressive MS (MS-MSC) have reduced expansion potential, premature senescence, and reduced neuroprotective potential in vitro. In view of the role of antioxidants in ageing and neuroprotection, we examined the antioxidant capacity of MS-MSC demonstrating that MS-MSC secretion of antioxidants superoxide dismutase 1 (SOD1) and glutathione S-transferase P (GSTP) is reduced and correlates negatively with the duration of progressive phase of MS...
July 31, 2018: Stem Cells Translational Medicine
Gerhard Bauer, Magdi Elsallab, Mohamed Abou-El-Enein
The promise of stem cell (SC) therapies to restore functions of damaged tissues and organs brings enormous hope to patients, their families, loved ones and caregivers. However, limits may exist for which indications SC therapies might be useful, efficacious, and safe. Applications of innovative therapies within regulatory boundaries and within the framework of controlled clinical trials are the norm in the scientific and medical community; such a system minimizes patient risk by setting a clear and acceptable safety and efficacy profile for new therapeutics before marketing authorization...
July 31, 2018: Stem Cells Translational Medicine
Qixing Zhong, Filip Laco, Mei-Chih Liao, Tsung L Woo, Steve K W Oh, Christina L L Chai
In this study, 50 tri-substituted imidazoles (TIs), which are analogs of the small molecules TA-01 and SB203580, were synthesized and screened for cardiomyogenic activities. Several TIs displayed cardiomyogenic activities when applied during the differentiation from days 3-5. The TIs did not affect the Wnt/β-catenin pathway during cardiomyogenesis and the likely mechanism of action is through the inhibition of ALK5 of the TGFβ pathway. Interestingly, these TIs promoted the neural differentiation of human pluripotent stem cells (hPSCs) with a similar potency to that of the dual SMAD inhibitors SB431542/LDN-193189 when dosed from days 1 to 9...
July 31, 2018: Stem Cells Translational Medicine
Takayasu Ohtake, Yasuhiro Mochida, Kunihiro Ishioka, Machiko Oka, Kyoko Maesato, Hidekazu Moriya, Sumi Hidaka, Satoshi Higashide, Tetsuya Ioji, Yasuyuki Fujita, Atsuhiko Kawamoto, Masanori Fukushima, Shuzo Kobayashi
Critical limb ischemia (CLI) is a devastating disease in patients undergoing hemodialysis (HD). Based on the unsatisfactory results of autologous mononuclear cell transplantation for patients with CLI undergoing HD, we conducted a phase II clinical trial to evaluate the safety and efficacy of granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood-derived autologous purified CD34 positive (CD34+) cell transplantation for CLI in patients undergoing HD. Six patients with CLI (two with Rutherford category 4 and four with Rutherford category 5) were enrolled...
July 30, 2018: Stem Cells Translational Medicine
Offer Zeira, Simone Scaccia, Letizia Pettinari, Erica Ghezzi, Nimrod Asiag, Laura Martinelli, Daniele Zahirpour, Maria P Dumas, Martin Konar, Davide M Lupi, Laurence Fiette, Luisa Pascucci, Leonardo Leonardi, Alistair Cliff, Giulio Alessandri, Augusto Pessina, Daniele Spaziante, Marina Aralla
Similar to the disease affecting humans, osteoarthritis (OA) is a painful musculoskeletal condition affecting 20% of the adult canine population. Several solutions have been proposed, but the results achieved to date are far from being satisfactory. New approaches, such as intra-articular delivery of cells (including mesenchymal stromal cells), have been proposed. Among the many sources, the adipose tissue is considered very promising. We evaluated the safety, feasibility, and efficacy of a single intra-articular injection of autologous and micro-fragmented adipose tissue (MFAT) in 130 dogs with spontaneous OA...
July 23, 2018: Stem Cells Translational Medicine
Guihua Liu, Rongpei Wu, Bin Yang, Chunhua Deng, Xiongbing Lu, Stephen J Walker, Peter X Ma, Steve Mou, Anthony Atala, Yuanyuan Zhang
Endothelial cells (ECs) play a key role in revascularization within regenerating tissue. Stem cells are often used as an alternative cell source when ECs are not available. Several cell types have been used to give rise to ECs, such as umbilical cord vessels, or differentiated from somatic stem cells, embryonic, or induced pluripotent stem cells. However, the latter carry the potential risk of chronic immune rejection and oncogenesis. Autologous endothelial precursors are an ideal resource, but currently require an invasive procedure to obtain them from the patient's own blood vessels or bone marrow...
July 16, 2018: Stem Cells Translational Medicine
Joshua G Hunsberger, Thomas Shupe, Anthony Atala
Regenerative medicine is poised to become a significant industry within the medical field. As such, the development of strategies and technologies for standardized and automated regenerative medicine clinical manufacturing has become a priority. An industry-driven roadmap toward industrial scale clinical manufacturing was developed over a 3-year period by a consortium of companies with significant investment in the field of regenerative medicine. Additionally, this same group identified critical roadblocks that stand in the way of advanced, large-scale regenerative medicine clinical manufacturing...
July 15, 2018: Stem Cells Translational Medicine
Maximilian Boesch, Gilbert Spizzo, Andreas Seeber
Colorectal cancer (CRC) is one of the most common malignancies worldwide. In spite of various attempts to ameliorate outcome by escalating treatment, significant improvement is lacking particularly in the adjuvant setting. It has been proposed that cancer stem cells (CSCs) and the epithelial-to-mesenchymal transition (EMT) are at least partially responsible for therapy resistance in CRC. The epithelial cell adhesion molecule (EpCAM) was one of the first CSC antigens to be described. Furthermore, an EpCAM-specific antibody (edrecolomab) has the merit of having launched the era of monoclonal antibody treatment in oncology in the 1990s...
June 2018: Stem Cells Translational Medicine
Golnar Shojaati, Irona Khandaker, Kyle Sylakowski, Martha L Funderburgh, Yiqin Du, James L Funderburgh
Stem cells from human corneal stroma (CSSC) suppress corneal stromal scarring in a mouse wound-healing model and promote regeneration of native transparent tissue (PMID:25504883). This study investigated efficacy of compressed collagen gel (CCG) as a vehicle to deliver CSSC for corneal therapy. CSSC isolated from limbal stroma of human donor corneas were embedded in soluble rat-tendon collagen, gelled at 37°C, and partially dehydrated to a thickness of 100 µm by passive absorption. The CCG disks were dimensionally stable, easy to handle, and could be adhered securely to de-epithelialized mouse cornea with fibrin-based adhesive...
June 2018: Stem Cells Translational Medicine
Sirikul Soontararak, Lyndah Chow, Valerie Johnson, Jonathan Coy, William Wheat, Daniel Regan, Steven Dow
Cellular therapy with allogeneic or autologous mesenchymal stem cells (MSC) has emerged as a promising new therapeutic strategy for managing inflammatory bowel disease (IBD). However, MSC therapy ideally requires a convenient and relatively homogenous cell source (typically bone marrow or adipose tissues) and the ability to generate cells with stable phenotype and function. An alternative means of generating allogeneic MSC is to derive them from induced pluripotent stem cells (iPSC), which could in theory provide an indefinite supply of MSC with well-defined phenotype and function...
June 2018: Stem Cells Translational Medicine
Daniel Poppe, Jonas Doerr, Marion Schneider, Ruven Wilkens, Julius A Steinbeck, Julia Ladewig, Allison Tam, David E Paschon, Philip D Gregory, Andreas Reik, Christa E Müller, Philipp Koch, Oliver Brüstle
As a powerful regulator of cellular homeostasis and metabolism, adenosine is involved in diverse neurological processes including pain, cognition, and memory. Altered adenosine homeostasis has also been associated with several diseases such as depression, schizophrenia, or epilepsy. Based on its protective properties, adenosine has been considered as a potential therapeutic agent for various brain disorders. Since systemic application of adenosine is hampered by serious side effects such as vasodilatation and cardiac suppression, recent studies aim at improving local delivery by depots, pumps, or cell-based applications...
June 2018: Stem Cells Translational Medicine
Alborz Karimzadeh, Vanessa M Scarfone, Erika Varady, Connie Chao, Karin Grathwohl, John W Fathman, David A Fruman, Thomas Serwold, Matthew A Inlay
Hematopoietic stem cells (HSCs) are the self-renewing multipotent progenitors to all blood cell types. Identification and isolation of HSCs for study has depended on the expression of combinations of surface markers on HSCs that reliably distinguish them from other cell types. However, the increasing number of markers required to isolate HSCs has made it tedious, expensive, and difficult for newcomers, suggesting the need for a simpler panel of HSC markers. We previously showed that phenotypic HSCs could be separated based on expression of CD11a and that only the CD11a negative fraction contained true HSCs...
June 2018: Stem Cells Translational Medicine
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