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Stem cell treatments

Odd L Gammelgaard, Mikkel G Terp, Birgitte Preiss, Henrik J Ditzel
Immunotherapy is one of the most promising cancer treatment modalities, but the lack of appropriate preclinical in vivo models hampers the development of novel immunotherapeutic strategies. Here, we studied the ability of transplanted human cancer cells to form primary tumors and metastasize in humanized immune system mice created by transfer of CD34+ human hematopoietic stem cells. All tested transplanted cancer cell lines developed primary tumors that progressed nearly synchronously. Spontaneous lung and liver metastases developed from both orthotopic and ectotopic transplanted cancer cells, and the ability to spread inversely correlated with the extent of CD8+ infiltration in the primary tumor...
August 18, 2018: Molecular Oncology
Toshimitsu Otani, Daigo Ochiai, Hirotaka Masuda, Yushi Abe, Marie Fukutake, Tadashi Matsumoto, Kei Miyakoshi, Mamoru Tanaka
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains a major cause of cerebral palsy. Increasing evidence has suggested that mesenchymal stem cells have a favorable effect on HIE. However, the efficacy of human amniotic fluid stem cells (hAFS) for HIE, especially in the chronic phase, remains unclear. The aim of this study was to determine the neurorestorative effect of hAFS on the chronic phase of HIE. METHODS: hAFS were isolated from AF cells as CD117-positive cells...
August 10, 2018: Pediatric Research
Ingmar Glauche, Matthias Kuhn, Christoph Baldow, Philipp Schulze, Tino Rothe, Hendrik Liebscher, Amit Roy, Xiaoning Wang, Ingo Roeder
Longitudinal monitoring of BCR-ABL transcript levels in peripheral blood of CML patients treated with tyrosine kinase inhibitors (TKI) revealed a typical biphasic response. Although second generation TKIs like dasatinib proved more efficient in achieving molecular remission compared to first generation TKI imatinib, it is unclear how individual responses differ between the drugs and whether mechanisms of drug action can be deduced from the dynamic data. We use time courses from the DASISION trial to address statistical differences in the dynamic response between first line imatinib vs...
August 17, 2018: Scientific Reports
Krishanthy Sornalingam, Ahmed Javed, Tariq Aslam, Panagiotis Sergouniotis, Simon Jones, Arunabha Ghosh, Jane Ashworth
PURPOSE: Mucopolysaccharidoses (MPSs) are a heterogeneous group of lysosomal storage disorders. Ocular complications (such as corneal clouding, retinopathy and optic neuropathy) are common. Notably, there is a paucity of data on the effect of genotype and systemic treatments (enzyme replacement therapy or haematopoietic stem cell transplantation) on the ocular phenotype in MPS. We prospectively studied the ocular features of patients with MPSI (Hurler/Hurler-Scheie/Scheie), MPSIV (Morquio) and MPSVI (Maroteaux-Lamy), to evaluate the effect of different therapeutic interventions and to correlate the findings with genetic and biomarker data...
August 17, 2018: British Journal of Ophthalmology
Brian Ball, Rami S Komrokji, Lionel Adès, Mikkael A Sekeres, Amy E DeZern, Lisa Pleyer, Norbert Vey, Antonio Almeida, Ulrich Germing, Thomas Cluzeau, Uwe Platzbecker, Steven D Gore, Pierre Fenaux, Thomas Prebet
Hypomethylating agent (HMA) failure in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) carries a poor prognosis with limited treatment options. Although intensive, remission induction chemotherapy is often used subsequently, in particular to bridge to allogeneic transplantation, it is not clear whether an advantage exists for any particular regimen. Based on an international collaboration, we retrospectively analyzed induction response rate and survival in 366 patients after HMA failure. Patients received 7+3, intermediate- to high-dose cytarabine (IDAC), or purine nucleoside analog-based regimens...
August 28, 2018: Blood Advances
Yun-Zhong Nie, Yun-Wen Zheng, Kei Miyakawa, Soichiro Murata, Ran-Ran Zhang, Keisuke Sekine, Yasuharu Ueno, Takanori Takebe, Takaji Wakita, Akihide Ryo, Hideki Taniguchi
Therapies against hepatitis B virus (HBV) have improved in recent decades; however, the development of individualized treatments has been limited by the lack of individualized infection models. In this study, we used human induced pluripotent stem cell (hiPSC) to generate a functional liver organoid (LO) that inherited the genetic background of the donor, and evaluated its application in modeling HBV infection and exploring virus-host interactions. To establish a functional hiPSC-LO, we cultured hiPSC-derived endodermal, mesenchymal, and endothelial cells with a chemically defined medium in a three-dimensional microwell culture system...
August 14, 2018: EBioMedicine
Tzu-Chuan Huang, Shang-Yi Huang, Ming Yao, Chen-Yuan Lin, Wen-Li Hwang, Jyh-Pyng Gau, Tran-Der Tan, Po-Nan Wang, Yi-Chang Liu, Shih-Chiang Lin, Ruey-Ho Kao, Sung-Nan Pei, Ming-Sun Yu, Hsuan-Yu Lin, Yung-Cheng Su, Chih-Cheng Chen, Sin-Syue Li, Yi-Ying Wu
BACKGROUND/PURPOSE: Multiple myeloma (MM) is a monoclonal plasma cell malignancy. The primary choice of treatment for MM is induction therapy followed by autologous stem cell transplantation (ASCT). This study aimed to analyze the treatment efficacy of ASCT in a Taiwanese cohort and evaluate possible prognostic factors. METHODS: From the database of the Taiwan Blood and Marrow Transplantation registry, data on 396 patients with MM who underwent ASCT were reviewed...
August 14, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
Byoung-San Moon, Wange Lu, Hong Ju Park
Hearing loss occurs with the loss of hair cells of the cochlea and subsequent degeneration of spiral ganglion neurons (SGNs). Regeneration of SGNs is a potentially promising therapeutic approach to hearing loss in addition to the use of a cochlear implant (CI), because this device stimulates SGNs directly to restore hearing bypassing the missing hair cells. The presence of SGN-neural stem cells (NSCs) has been reported in adult human and mice. These cells have the potential to become SGNs and thus represent a cellular foundation for regeneration therapies for hearing loss...
August 14, 2018: Biochemical and Biophysical Research Communications
Brian G Ballios, Maxwell Weisbrod, Clara C Chan, Armand Borovik, Jeffrey R Schiff, Kathryn J Tinckam, Atul Humar, S Joseph Kim, Edward H Cole, Allan R Slomovic
The objective of this study was to evaluate systemic immunosuppression regimens used for patients undergoing ocular surface stem cell transplantation, including their benefits and adverse effects in the adjunctive management of limbal stem cell deficiency (LSCD). A systematic literature review was conducted using the MEDLINE and EMBASE databases (1980-2015). Data were collected on surgical intervention(s), type of immunosuppressive agent(s), duration of immunosuppression, percentage with stable ocular surface at last follow-up, mean follow-up time, and demographics...
August 2018: Canadian Journal of Ophthalmology. Journal Canadien D'ophtalmologie
Laura Barrachina, Ana Rosa Remacha, Antonio Romero, Arantza Vitoria, Jorge Albareda, Marta Prades, Mercedes Roca, Pilar Zaragoza, Francisco José Vázquez, Clementina Rodellar
BACKGROUND: This study aimed at assessing the effectiveness and safety of repeated administrations of allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) primed with tumor necrosis factor (TNF)-α and interferon-γ in an equine model of chemically-induced osteoarthritis. Arthritis was induced in both radio-carpal (RC)-joints by amphotericin-B in 18 ponies, divided into three groups depending on the treatment injected: MSC-naïve (n = 7), MSC-primed (n = 7) and control (n = 4)...
August 17, 2018: BMC Veterinary Research
Nur Soyer, Püsem Patır, Ayşe Uysal, Mustafa Duran, Hatice Demet Ünal, Raika Durusoy, Murat Tombuloğlu, Fahri Şahin, Mahmut Töbü, Filiz Vural, Güray Saydam
Background/aim: In Turkey, lenalidomide plus dexamethasone (RD) has been used to treat relapsed/refractory multiple myeloma (RRMM) since 2010. This retrospective, single-center study evaluated the efficacy and tolerability of RD in patients with RRMM between October 2010 and June 2016. Materials and methods: Patients’ records were reviewed, and overall (OS) and progression-free survival (PFS) were assessed. Results: One hundred and twenty patients (71 males; 59...
August 16, 2018: Turkish Journal of Medical Sciences
Miao Wang, Juan Jiang, Yi Cai, Min Zhao, Qijuan Wu, Yannan Cui, Chunjie Zhao
Posaconazole (PCZ) is a triazole antifungal agent with an extended spectrum of antifungal activity. It is approved for the prophylaxis of invasive fungal infections in patients with neutropenia or in haematopoietic stem cell transplant recipients undergoing high-dose immunosuppressive therapy for graft-versus-host disease, and for the treatment of fungal infections. However, its pharmacological effects are severely limited owing to its poor solubility and low bioavailability. In order to solve these problems, a sulfobutyl ether-β-cyclodextrin (SBE-β-CD) compound was used to prepare an intramuscular injection to improve the bioavailability of posaconazole...
August 17, 2018: Biomedical Chromatography: BMC
Jennifer H Shepherd, Daniel Howard, Amie K Waller, Holly Rebecca Foster, Annett Muller, Thomas Moreau, Amanda L Evans, Meera Arumugam, Guénaëlle Bouët Chalon, Eleonora Vriend, Natalia Davidenko, Cedric Ghevaert, Serena M Best, Ruth E Cameron
Platelet transfusions are a key treatment option for a range of life threatening conditions including cancer, chemotherapy and surgery. Efficient ex vivo systems to generate donor independent platelets in clinically relevant numbers could provide a useful substitute. Large quantities of megakaryocytes (MKs) can be produced from human pluripotent stem cells, but in 2D culture the ratio of platelets harvested from MK cells has been limited and restricts production rate. The development of biomaterial cell supports that replicate vital hematopoietic micro-environment cues are one strategy that may increase in vitro platelet production rates from iPS derived Megakaryocyte cells...
August 8, 2018: Biomaterials
Mohamed Gadelkarim, Abdelrahman Ibrahim Abushouk, Esraa Ghanem, Ali Mohamed Hamaad, Anas M Saad, Mohamed M Abdel-Daim
With the increasing global prevalence of diabetes mellitus, a significant rise in the number of patients suffering from non-healing wounds is expected. However, available treatments, such as revascularization surgery and foot care education are often insufficient to ensure satisfactory wound healing. One therapeutic strategy that has been identified as particularly promising utilizes adipose-derived stem cells (ADSCs). Through a comprehensive literature search of published and ongoing studies, we aimed to provide an overview of the experimental basis, the scientific background, and advances in the delivery of ADSCs for treating non-healing diabetic wounds...
August 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Fedja Farowski, Gregor Els, Anastasia Tsakmaklis, Paul G Higgins, Christian R Kahlert, Christoph K Stein-Thoeringer, Johanna S Bobardt, Katja Dettmer-Wilde, Peter J Oefner, Jörg Janne Vehreschild, Maria J G T Vehreschild
OBJECTIVES: After allogeneic hematopoietic stem cell transplantation (allo-HCT), urinary levels of 3-indoxyl sulfate (3-IS) correlate with the relative abundance of bacteria from the class Clostridia (RAC), and antibiotic treatment is considered the major determinant of this outcome. A high RAC has been associated with favorable outcome after allo-HCT and protection from Clostridium difficile infection (CDI). We assessed correlations between alpha diversity, RAC and urinary 3-IS levels in a non-allo-HCT clinical cohort of antibiotic treated patients to further explore 3-IS as a biomarker of reduced diversity and predisposition to CDI...
August 17, 2018: Gut Microbes
Jing Hao, Andrew Godley, Jocelyn D Shoemake, Zheyi Han, Anthony Magnelli, Jennifer S Yu
Radiation therapy is an integral part of treatment for patients with glioblastoma. New technological advances in linear accelerators have made extra-high dose rate irradiation possible. This shortens patient treatment time significantly compared to standard dose rate irradiation, but the biologic effects of extra high dose rate irradiation are poorly understood. Glioma stem-like cells (GSCs) are resistant to standard radiation and contribute to tumor progression. Here, we assess the therapeutic effect of extra high dose rate vs...
2018: PloS One
Rekha Pal, Ning Wei, Nan Song, Shaoyu Wu, Rim S Kim, Ying Wang, Patrick G Gavin, Peter C Lucas, Ashok Srinivasan, Carmen J Allegra, Samuel A Jacobs, Soonmyung Paik, John C Schmitz, Katherine L Pogue-Geile
Molecular subtypes of colorectal tumors are associated with prognosis and prediction for treatment benefit from chemotherapy. The purpose of this study was two-fold: 1) to determine the association of colorectal (CRC) molecular subtypes with response to targeted therapies in pre-clinical models and 2) to identify treatments for CRC stem-like subtype because these tumors are associated with a very poor patient prognosis. Eleven CRC cell lines were classified into molecular subtypes and tested for their response to pan-ERBB, MEK, and ERK inhibitors as single agents and in combination...
2018: PloS One
Akitsu Kawabe, Shinichi Matsumoto, Masayuki Shimoda
BACKGROUND: New methods of beta-cell replacement have been developed to maintain excellent glycemic control, improve quality of life, and even eliminate insulin injections in patients with type 1 diabetes mellitus (T1DM). Previously, we demonstrated that being insulin-free is the strongest motivation for accepting a newly developed therapy. Multiple allogeneic islet transplantations with immunosuppression using a human donor is the best option to be insulin-free, but the necessity for immunosuppression and donor shortage are major issues...
August 17, 2018: Islets
Daniel Kerr Ii, Lubomir Sokol
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematopoietic malignancy that contributes to < 1% of all hematologic malignancies. Before the introduction of various targeted agents, the therapeutic approach was based on regimens used for acute lymphoblastic or myeloid leukemia and non-Hodgkin's lymphoma (e.g., hyperCVAD and CHOP-based regimens) followed by allogeneic stem cell transplantation for eligible patients. Given that this disease primarily affects older patients, there is a significant barrier to using these highly toxic regimens, even though these regimens are usually associated with the most durable response...
August 17, 2018: Expert Opinion on Investigational Drugs
Kaiyue Zhang, Xiangnan Zhao, Xiaoniao Chen, Yongzhen Wei, Wei Du, Yuebing Wang, Linan Liu, Weian Zhao, Zhibo Han, Deling Kong, Qiang Zhao, Zhikun Guo, Zhongchao Han, Na Liu, Fengxia Ma, Zongjin Li
Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for cell-free treatment of various diseases. However, maintaining the retention and stability of exosomes over time in vivo after transplantation is a major challenge in clinical application of MSC-derived exosomes. Here, we investigated if human placenta-derived MSCs (hP-MSCs) derived exosomes incorporated with chitosan hydrogel could boost the retention and stability of exosomes and further enhance their therapeutic effects...
August 17, 2018: ACS Applied Materials & Interfaces
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