Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis
This study shows that a single dose of minimally expanded mesenchymal stromal cells (MSCs) injected systemically into a mouse model of human age-related osteoporosis display long-term engraftment and prevent the decline in bone formation, bone quality, and microarchitectural competence. This work adds to a growing body of evidence suggesting that the decline of MSCs associated with age-related osteoporosis is a major transformative event in the progression of the disease. Furthermore, it establishes proof of concept that MSC transplantation may be a viable therapeutic strategy to treat or prevent human age-related osteopor...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Kiernan, J., Hu, S., Grynpas, M. D., Davies, J. E., Stanford, W. L. Tags: Tissue Engineering and Regenerative Medicine, Mesenchymal Stem Cells Source Type: research
Chondroitin Sulfate Immobilized on a Biomimetic Scaffold Modulates Inflammation While Driving Chondrogenesis
Costs associated with degenerative inflammatory conditions of articular cartilage are exponentially increasing in the aging population, and evidence shows a strong clinical need for innovative therapies. Stem cell-based therapies represent a promising strategy for the treatment of innumerable diseases. Their regenerative potential is undeniable, and it has been widely exploited in many tissue-engineering approaches, especially for bone and cartilage repair. Their immune-modulatory capacities in particular make stem cell-based therapeutics an attractive option for treating inflammatory diseases. However, because of their gr...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Corradetti, B., Taraballi, F., Minardi, S., Van Eps, J., Cabrera, F., Francis, L. W., Gazze, S. A., Ferrari, M., Weiner, B. K., Tasciotti, E. Tags: Tissue Engineering and Regenerative Medicine, Mesenchymal Stem Cells Source Type: research
Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived Cardiomyocytes Compatible With Global Distribution of Cells for Clinical Applications and Toxicology Testing
This study established effective clinically compatible strategies for cold (4°C) storage of hPSC-CMs cultured as two-dimensional (2D) monolayers and three-dimensional (3D) aggregates. Cell recovery of 2D monolayers of hPSC-CMs was found to be dependent on the time of storage, and 3D cell aggregates were more resistant to prolonged cold storage than 2D monolayers. Of note, it was demonstrated that 7 days of cold storage did not affect hPSC-CM ultrastructure, phenotype, or function. This study provides important insights into the cold preservation of PSC-CMs that could be valuable in improving global commercial distribut...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Correia, C., Koshkin, A., Carido, M., Espinha, N., Šarić, T., Lima, P. A., Serra, M., Alves, P. M. Tags: Protocols and Manufacturing for Cell-Based Therapies, Cardiac Stem Cells Source Type: research
Residual {beta}-Cell Function Predicts Clinical Response After Autologous Hematopoietic Stem Cell Transplantation
In conclusion, HOMA-IR and QUICKI could be optimal measurements for β-cell reserves, and they were predictive for the clinical response after auto-HSCT.
Significance
The β-score was comprehensive and reliable in evaluating clinical response after autologous hematopoietic stem cell transplantation (HSCT). The homeostasis model assessments for insulin resistance and the quantitative insulin sensitivity check index could serve as precise assessments for residual β-cell function and good predictors of clinical response. They might be used to select optimal clinical trial participants or predict the clinical res...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Xiang, H., Yang, C., Xiang, T., Wang, Z., Ge, X., Li, F., Su, Y., Chen, H., Huang, X., Zeng, Q. Tags: Mesenchymal Stem Cells, Standards, Policies, Protocols, and Regulations for Cell-Based Therapies Source Type: research
Epicardium-Derived Cells Formed After Myocardial Injury Display Phagocytic Activity Permitting In Vivo Labeling and Tracking
This study demonstrates that EPDCs formed after MI display strong endocytic activity to take up i.v.-injected labeled nanoemulsions. This feature permitted in vivo labeling and tracking of EPDCs, demonstrating their role in myo- and vasculogenesis. The newly discovered endocytic activity permits in vivo imaging of EPDCs with 19F-MRI and may be used for the liposomal delivery of substances to further study their reparative potential.
Significance
The present study reports that epicardium-derived cells (EPDCs) formed after myocardial infarction can specifically endocytose nanoparticles in vivo and in vitro. This novel featu...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Ding, Z., Temme, S., Quast, C., Friebe, D., Jacoby, C., Zanger, K., Bidmon, H.-J., Grapentin, C., Schubert, R., Flogel, U., Schrader, J. Tags: Cardiac Stem Cells, Enabling Technologies for Cell-Based Clinical Translation Source Type: research
Efficacy of CD34+ Stem Cell Therapy in Nonischemic Dilated Cardiomyopathy Is Absent in Patients With Diabetes but Preserved in Patients With Insulin Resistance
We evaluated the association of diabetes and insulin resistance with the response to cell therapy in patients with nonischemic dilated cardiomyopathy (DCM). A total of 45 outpatients with DCM received granulocyte colony-stimulating factor for 5 days. CD34+ cells were then collected by apheresis and injected transendocardially. Twelve patients had diabetes mellitus (DM group), 17 had insulin resistance (IR group), and 16 displayed normal glucose metabolism (no-IR group). After stimulation, we found higher numbers of CD34+ cells in the IR group (94 ± 73 x 106 cells per liter) than in the no-IR group (54 ± 35 x ...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Vrtovec, B., Sever, M., Jensterle, M., Poglajen, G., Janez, A., Kravos, N., Zemljic, G., Cukjati, M., Cernelc, P., Haddad, F., Wu, J. C., Jorde, U. P. Tags: Mesenchymal Stem Cells, Enabling Technologies for Cell-Based Clinical Translation Source Type: research
Development of a Functional Biomarker for Use in Cell-Based Therapy Studies in Seropositive Rheumatoid Arthritis
Cell-based therapy has potential therapeutic value in autoimmune diseases such as rheumatoid arthritis (RA). In RA, reduction of disease activity has been associated with improvement in the function of regulatory T cells (Treg) and attenuated responses of proinflammatory effector T cells (Teff). Mesenchymal stem cells (MSCs) and related multipotent adult progenitor cells (MAPC) have strong anti-inflammatory and immunomodulatory properties and may be able to "reset" the immune system to a pre-RA state. MAPC are MSC-like cells that are slightly earlier in lineage, have greater expansion capacity, and can be used as "off-the-...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Shalev-Malul, G., Soler, D. C., Ting, A. E., Lehman, N. A., Barnboym, E., McCormick, T. S., Anthony, D. D., Lazarus, H. M., Caplan, A. I., Breitman, M., Singer, N. G. Tags: Mesenchymal Stem Cells, Enabling Technologies for Cell-Based Clinical Translation Source Type: research
High-Throughput Phenotypic Screening of Human Astrocytes to Identify Compounds That Protect Against Oxidative Stress
This study is the largest-scale high-throughput screen conducted using human astrocytes, with a total of 17,536 data points collected in the primary screen. The results demonstrate the relevancy and utility of using astrocytes differentiated from human stem cells as a disease model for drug discovery and development. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Thorne, N., Malik, N., Shah, S., Zhao, J., Class, B., Aguisanda, F., Southall, N., Xia, M., McKew, J. C., Rao, M., Zheng, W. Tags: Embryo Development, Cell-Based Drug Development, Screening, and Toxicology Source Type: research
Functional and Transcriptional Characterization of Histone Deacetylase Inhibitor-Mediated Cardiac Adverse Effects in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
This study found that human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) can predict cardiac adverse events in patients caused by HDAC inhibitors. Furthermore, transcriptional changes at the level of gene expression supported the effects on the beating properties of hiPS-CMs and highlight targets that might cause these cardiac adverse effects. hiPS-CMs represent a valuable translational model to assess HDAC inhibitor-mediated cardiotoxicity and to support development of safer HDAC inhibitors. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Kopljar, I., Gallacher, D. J., De Bondt, A., Cougnaud, L., Vlaminckx, E., Van den Wyngaert, I., Lu, H. R. Tags: Pluripotent Stem Cells, Cell-Based Drug Development, Screening, and Toxicology Source Type: research
Massive Clonal Selection and Transiently Contributing Clones During Expansion of Mesenchymal Stem Cell Cultures Revealed by Lentiviral RGB-Barcode Technology
Mesenchymal stem (or stromal) cells (MSCs) have been used in more than 400 clinical trials for the treatment of various diseases. The clinical benefit and reproducibility of results, however, remain extremely variable. During the in vitro expansion phase, which is necessary to achieve clinically relevant cell numbers, MSCs show signs of aging accompanied by different contributions of single clones to the mass culture. Here we used multicolor lentiviral barcode labeling to follow the clonal dynamics during in vitro MSC expansion from whole umbilical cord pieces (UCPs). The clonal composition was analyzed by a combination of...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Selich, A., Daudert, J., Hass, R., Philipp, F., von Kaisenberg, C., Paul, G., Cornils, K., Fehse, B., Rittinghausen, S., Schambach, A., Rothe, M. Tags: Mesenchymal Stem Cells, Tissue-Specific Progenitor and Stem Cells Source Type: research
Rapamycin-Induced Hypoxia Inducible Factor 2A Is Essential for Chondrogenic Differentiation of Amniotic Fluid Stem Cells
Amniotic fluid stem (AFS) cells represent a major source of donor cells for cartilage repair. Recently, it became clear that mammalian target of rapamycin (mTOR) inhibition has beneficial effects on cartilage homeostasis, but the effect of mTOR on chondrogenic differentiation is still elusive. Therefore, the objectives of this study were to investigate the effects of mammalian target of rapamycin complex 1 (mTORC1) modulation on the expression of SOX9 and on its downstream targets during chondrogenic differentiation of AFS cells. We performed three-dimensional pellet culturing of AFS cells and of in vitro-expanded, human-d...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Preitschopf, A., Schorghofer, D., Kinslechner, K., Schutz, B., Zwickl, H., Rosner, M., Joo, J. G., Nehrer, S., Hengstschlager, M., Mikula, M. Tags: Amniotic Stem Cells, Fetal and Neonatal Stem Cells Source Type: research
Modeling Cystic Fibrosis Using Pluripotent Stem Cell-Derived Human Pancreatic Ductal Epithelial Cells
We established an efficient strategy to direct human pluripotent stem cells, including human embryonic stem cells (hESCs) and an induced pluripotent stem cell (iPSC) line derived from patients with cystic fibrosis, to differentiate into pancreatic ductal epithelial cells (PDECs). After purification, more than 98% of hESC-derived PDECs expressed functional cystic fibrosis transmembrane conductance regulator (CFTR) protein. In addition, iPSC lines were derived from a patient with CF carrying compound frameshift and mRNA splicing mutations and were differentiated to PDECs. PDECs derived from Weill Cornell cystic fibrosis (WCC...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Simsek, S., Zhou, T., Robinson, C. L., Tsai, S.-Y., Crespo, M., Amin, S., Lin, X., Hon, J., Evans, T., Chen, S. Tags: Pluripotent Stem Cells, Pluripotent Stem Cells, Mesenchymal Stem Cells Source Type: research
Genetic Correction of Induced Pluripotent Stem Cells From a Deaf Patient With MYO7A Mutation Results in Morphologic and Functional Recovery of the Derived Hair Cell-Like Cells
The genetic correction of induced pluripotent stem cells (iPSCs) induced from somatic cells of patients with sensorineural hearing loss (caused by hereditary factors) is a promising method for its treatment. The correction of gene mutations in iPSCs could restore the normal function of cells and provide a rich source of cells for transplantation. In the present study, iPSCs were generated from a deaf patient with compound heterozygous MYO7A mutations (c.1184G>A and c.4118C>T; P-iPSCs), the asymptomatic father of the patient (MYO7A c.1184G>A mutation; CF-iPSCs), and a normal donor (MYO7AWT/WT; C-iPSCs). One of MYO7...
Source: Stem Cells Translational Medicine - April 17, 2016 Category: Stem Cells Authors: Tang, Z.-H., Chen, J.-R., Zheng, J., Shi, H.-S., Ding, J., Qian, X.-D., Zhang, C., Chen, J.-L., Wang, C.-C., Li, L., Chen, J.-Z., Yin, S.-K., Huang, T.-S., Chen, P., Guan, M.-X., Wang, J.-F. Tags: Pluripotent Stem Cells, Pluripotent Stem Cells Source Type: research
WNT-C59, a Small-Molecule WNT Inhibitor, Efficiently Induces Anterior Cortex That Includes Cortical Motor Neurons From Human Pluripotent Stem Cells
The recapitulation of human neural development in a controlled, defined manner from pluripotent stem cells (PSCs) has considerable potential for studies of human neural development, circuit formation and function, and the construction of in vitro models of neurological diseases. The inhibition of Wnt signaling, often by the recombinant protein DKK1, is important for the induction of cortical neurons. Here, we report a novel differentiation method using a small-molecule WNT inhibitor, WNT-C59 (C59), to efficiently induce human anterior cortex. We compared two types of small molecules, C59 and XAV939 (XAV), as substitutes fo...
Source: Stem Cells Translational Medicine - March 18, 2016 Category: Stem Cells Authors: Motono, M., Ioroi, Y., Ogura, T., Takahashi, J. Tags: Tissue Engineering and Regenerative Medicine, Pluripotent Stem Cells Source Type: research
Enhanced Osteogenesis of Adipose-Derived Stem Cells by Regulating Bone Morphogenetic Protein Signaling Antagonists and Agonists
This study demonstrates a novel strategy to maximize bone formation pathways in osteogenic differentiation of mesenchymal stem cells and functional bone formation by combining gene manipulation with a small molecule activator toward osteogenesis. The findings indicate promising stem cell-based therapy for treating bone defects that can effectively complement or replace current osteoinductive therapeutics. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - March 18, 2016 Category: Stem Cells Authors: Fan, J., Im, C. S., Guo, M., Cui, Z.-K., Fartash, A., Kim, S., Patel, N., Bezouglaia, O., Wu, B. M., Wang, C.-Y., Aghaloo, T. L., Lee, M. Tags: Tissue Engineering and Regenerative Medicine, Adipose-Derived Stem Cells Source Type: research
