Concise Review: Updated Advances and Current Challenges in Cell Therapy for Inborn Liver Metabolic Defects
The development of liver cell transplantation (LCT), considered a major biotechnological breakthrough, was intended to provide more accessible treatments for liver disease patients. By preserving the native recipient liver and decreasing hospitalization time, this innovative approach has progressively gained interest among clinicians. LCT initially targets inborn errors of liver metabolism, enabling the compensation of deficient metabolic functions for up to 18 months post-transplantation, supporting its use at least as a bridge to transplantation. The rigorous clinical development and widespread use of LCT depends strongl...
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Najimi, M., Defresne, F., Sokal, E. M. Tags: Concise Review, Tissue Engineering and Regenerative Medicine, Hepatic Stem Cells Source Type: research
Stepwise Differentiation of Mesenchymal Stem Cells Augments Tendon-Like Tissue Formation and Defect Repair In Vivo
Tendon injuries are common and present a clinical challenge, as they often respond poorly to treatment and result in long-term functional impairment. Inferior tendon healing responses are mainly attributed to insufficient or failed tenogenesis. The main objective of this study was to establish an efficient approach to induce tenogenesis of bone marrow-derived mesenchymal stem cells (BMSCs), which are the most common seed cells in tendon tissue engineering. First, representative reported tenogenic growth factors were used as media supplementation to induce BMSC differentiation, and the expression of teno-lineage transcripti...
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Yin, Z., Guo, J., Wu, T.-y., Chen, X., Xu, L.-l., Lin, S.-e., Sun, Y.-x., Chan, K.-M., Ouyang, H., Li, G. Tags: Tissue Engineering and Regenerative Medicine, Mesenchymal Stem Cells Source Type: research
Personalized Stem Cell Therapy to Correct Corneal Defects Due to a Unique Homozygous-Heterozygous Mosaicism of Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome
This study supports the rationale for the development of cultured autologous oral mucosal epithelial stem cell sheets obtained by selected heterozygous R311K-p63 stem cells, as an effective and personalized therapy for reconstructing the ocular surface of this unique case of EEC syndrome, thus bypassing gene therapy approaches.
Significance
This case demonstrates that in a somatic mosaicism context, a novel homozygous mutation in the p63 gene can arise as a consequence of an allelic gene conversion event, subsequent to a de novo mutation. The heterozygous mutant R311K-p63 stem cells can be isolated by means of clonal anal...
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Barbaro, V., Nasti, A. A., Raffa, P., Migliorati, A., Nespeca, P., Ferrari, S., Palumbo, E., Bertolin, M., Breda, C., Miceli, F., Russo, A., Caenazzo, L., Ponzin, D., Palu, G., Parolin, C., Di Iorio, E. Tags: Tissue Engineering and Regenerative Medicine, Skin-Derived Precursors/Progenitors Source Type: research
Generation of a Bone Organ by Human Adipose-Derived Stromal Cells Through Endochondral Ossification
In conclusion, despite their debated skeletal progenitor nature, human ASC can generate bone organs through ECO when suitably primed in vitro.
Significance
Recapitulation of endochondral ossification (ECO) (i.e., generation of marrow-containing ossicles through a cartilage intermediate) has relevance to develop human organotypic models for bone or hematopoietic cells and to engineer grafts for bone regeneration. This study demonstrated that expanded, human adult adipose-derived stromal cells can generate ectopic bone through ECO, as previously reported for bone marrow stromal cells. This system can be used as a model in a...
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Osinga, R., Di Maggio, N., Todorov, A., Allafi, N., Barbero, A., Laurent, F., Schaefer, D. J., Martin, I., Scherberich, A. Tags: Tissue Engineering and Regenerative Medicine, Adipose-Derived Stem Cells Source Type: research
Bone Marrow Mesenchymal Stem Cell-Based Engineered Cartilage Ameliorates Polyglycolic Acid/Polylactic Acid Scaffold-Induced Inflammation Through M2 Polarization of Macrophages in a Pig Model
This study demonstrated that bone marrow mesenchymal stem cell (BMSC)-based engineered cartilage could suppress inflammation by increasing M2 polarization of macrophages, resulting in better tissue survival in a pig model. Additionally, the effect of BMSC-based cartilage on the phenotype conversion of macrophages was further studied through an in vitro coculture system. This study could provide further support for the regeneration of cartilage engineering in immunocompetent animal models and provide new insight into the interaction of tissue-engineered cartilage and macrophages. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Ding, J., Chen, B., Lv, T., Liu, X., Fu, X., Wang, Q., Yan, L., Kang, N., Cao, Y., Xiao, R. Tags: Tissue Engineering and Regenerative Medicine, Mesenchymal Stem Cells Source Type: research
Apoptosis-Resistant Cardiac Progenitor Cells Modified With Apurinic/Apyrimidinic Endonuclease/Redox Factor 1 Gene Overexpression Regulate Cardiac Repair After Myocardial Infarction
In conclusion, antiapoptotic APE1-CPC graft, which increased TAK1-NF-B pathway activation, survived effectively in the ischemic heart, restored cardiac function, and reduced cardiac inflammation and fibrosis. APE1 overexpression in CPCs may serve as a novel strategy to improve cardiac cell therapy.
Significance
Improving the survival of cell grafts is essential to maximize the efficacy of cell therapy. The authors investigated the role of APE1 in CPCs under ischemic conditions and evaluated the therapeutic efficacy of transplanted APE1-overexpressing CPCs in a mouse model of myocardial infarction. APE1 hindered apoptosis ...
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Aonuma, T., Takehara, N., Maruyama, K., Kabara, M., Matsuki, M., Yamauchi, A., Kawabe, J.-i., Hasebe, N. Tags: Tissue Engineering and Regenerative Medicine, Cardiac Stem Cells Source Type: research
Adapting Preclinical Benchmarks for First-in-Human Trials of Human Embryonic Stem Cell-Based Therapies
This article reviews existing regulatory frameworks for preclinical requirements and assesses how their underlying principles may best be applied in the context of human embryonic stem cell-based interventions for the therapy of Parkinson's disease. This research will help to address the question of when it is ethically justified to start first-in-human trials in stem cell translational medicine. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Barazzetti, G., Hurst, S. A., Mauron, A. Tags: Embryo Development, Standards, Policies, Protocols, and Regulations for Cell-Based Therapies Source Type: research
Treatment With Human Whartons Jelly-Derived Mesenchymal Stem Cells Attenuates Sepsis-Induced Kidney Injury, Liver Injury, and Endothelial Dysfunction
The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks. Downregulation of endothelial nitric oxide synthase contributes to sepsis-induced endothelial dysfunction. Human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are known to reduce expression of proinflammatory cytokines and markers of apoptosis. We hypothesized that treatment with WJ-MSCs would protect renal, hepatic, and endothelial function in a cecal ligation and puncture (CLP) model of sepsis in rats. Rats were randomly divided into three groups: sham-operated rats; rats submitted to CLP and left untreated; and r...
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Condor, J. M., Rodrigues, C. E., Sousa Moreira, R. d., Canale, D., Volpini, R. A., Shimizu, M. H. M., Camara, N. O. S., Noronha, I. d. L., Andrade, L. Tags: Mesenchymal Stem Cells, Enabling Technologies for Cell-Based Clinical Translation Source Type: research
Epigenetic Library Screen Identifies Abexinostat as Novel Regulator of Adipocytic and Osteoblastic Differentiation of Human Skeletal (Mesenchymal) Stem Cells
The epigenetic mechanisms promoting lineage-specific commitment of human skeletal (mesenchymal or stromal) stem cells (hMSCs) into adipocytes or osteoblasts are still not fully understood. Herein, we performed an epigenetic library functional screen and identified several novel compounds, including abexinostat, which promoted adipocytic and osteoblastic differentiation of hMSCs. Using gene expression microarrays, chromatin immunoprecipitation for H3K9Ac combined with high-throughput DNA sequencing (ChIP-seq), and bioinformatics, we identified several key genes involved in regulating stem cell proliferation and differentiat...
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Ali, D., Hamam, R., Alfayez, M., Kassem, M., Aldahmash, A., Alajez, N. M. Tags: Mesenchymal Stem Cells, Tissue-Specific Progenitor and Stem Cells Cell-Based Drug Development, Screening, and Toxicology Source Type: research
Engineered Mesenchymal Cells Improve Passive Immune Protection Against Lethal Venezuelan Equine Encephalitis Virus Exposure
Mesenchymal stromal cells (MSCs) are being exploited as gene delivery vectors for various disease and injury therapies. We provide proof-of-concept that engineered MSCs can provide a useful, effective platform for protection against infectious disease. Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne pathogen affecting humans and equines and can be used in bio-warfare. No licensed vaccine or antiviral agent currently exists to combat VEEV infection in humans. Direct antibody administration (passive immunity) is an effective, but short-lived, method of providing immediate protection against a pathogen. We com...
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Braid, L. R., Hu, W.-G., Davies, J. E., Nagata, L. P. Tags: Mesenchymal Stem Cells, Tissue-Specific Progenitor and Stem Cells Source Type: research
Concise Review: Stem Cell Interventions for People With Cerebral Palsy: Systematic Review With Meta-Analysis
Evidence for stem cells as a potential intervention for cerebral palsy is emerging. Our objective was to determine the efficacy and safety of stem cells for improving motor and cognitive function of people with cerebral palsy. Searches were conducted in October 2015 in CENTRAL, EMBASE, MEDLINE, and Cochrane Libraries. Randomized controlled trials and controlled clinical trials of stem cells for cerebral palsy were included. Two authors independently decided upon included trials, extracted data, quality, and risk of bias. The primary outcome was gross motor function. Secondary outcomes were cognitive function and adverse ev...
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Novak, I., Walker, K., Hunt, R. W., Wallace, E. M., Fahey, M., Badawi, N. Tags: Concise Review, Cord Blood Stem Cells, Fetal and Neonatal Stem Cells Source Type: research
Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia
This study finds that umbilical cord-derived mesenchymal stromal cells transplanted by intracoronary delivery combined with two intravenous administrations was safe and could significantly improve left ventricular function, perfusion, and remodeling in a large-animal model of chronic myocardial ischemia, which provides a new choice for the no-option patients. In addition, this study used clinical-grade mesenchymal stem cells with delivery and assessment methods commonly used clinically to facilitate further clinical transformation. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Liu, C.-B., Huang, H., Sun, P., Ma, S.-Z., Liu, A.-H., Xue, J., Fu, J.-H., Liang, Y.-Q., Liu, B., Wu, D.-Y., Lu, S.-H., Zhang, X.-Z. Tags: Cord Blood Stem Cells, Fetal and Neonatal Stem Cells Source Type: research
Early Intravenous Delivery of Human Brain Stromal Cells Modulates Systemic Inflammation and Leads to Vasoprotection in Traumatic Spinal Cord Injury
This study demonstrates that these cells not only display a MSC phenotype in vitro but also have similar in vivo immunomodulatory effects after spinal cord injury that are more potent than those of non-central nervous system tissue-derived cells. Therefore, these cells are of great interest for therapeutic use in spinal cord injury. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Badner, A., Vawda, R., Laliberte, A., Hong, J., Mikhail, M., Jose, A., Dragas, R., Fehlings, M. Tags: Mesenchymal Stem Cells, Fetal and Neonatal Stem Cells Source Type: research
Enforced Expression of HOXB4 in Human Embryonic Stem Cells Enhances the Production of Hematopoietic Progenitors but Has No Effect on the Maturation of Red Blood Cells
We have developed a robust, Good Manufacturing Practice-compatible differentiation protocol capable of producing scalable quantities of red blood cells (RBCs) from human pluripotent stem cells (hPSCs). However, translation of this protocol to the clinic has been compromised because the RBCs produced are not fully mature; thus, they express embryonic and fetal, rather than adult globins, and they do not enucleate efficiently. Based on previous studies, we predicted that activation of exogenous HOXB4 would increase the production of hematopoietic progenitor cells (HPCs) from hPSCs and hypothesized that it might also promote ...
Source: Stem Cells Translational Medicine - July 19, 2016 Category: Stem Cells Authors: Jackson, M., Ma, R., Taylor, A. H., Axton, R. A., Easterbrook, J., Kydonaki, M., Olivier, E., Marenah, L., Stanley, E. G., Elefanty, A. G., Mountford, J. C., Forrester, L. M. Tags: Pluripotent Stem Cells, Pluripotent Stem Cells Source Type: research
Rapid Induction of Cerebral Organoids From Human Induced Pluripotent Stem Cells Using a Chemically Defined Hydrogel and Defined Cell Culture Medium
Tissue organoids are a promising technology that may accelerate development of the societal and NIH mandate for precision medicine. Here we describe a robust and simple method for generating cerebral organoids (cOrgs) from human pluripotent stem cells by using a chemically defined hydrogel material and chemically defined culture medium. By using no additional neural induction components, cOrgs appeared on the hydrogel surface within 10–14 days, and under static culture conditions, they attained sizes up to 3 mm in greatest dimension by day 28. Histologically, the organoids showed neural rosette and neural tube-like s...
Source: Stem Cells Translational Medicine - June 26, 2016 Category: Stem Cells Authors: Lindborg, B. A., Brekke, J. H., Vegoe, A. L., Ulrich, C. B., Haider, K. T., Subramaniam, S., Venhuizen, S. L., Eide, C. R., Orchard, P. J., Chen, W., Wang, Q., Pelaez, F., Scott, C. M., Kokkoli, E., Keirstead, S. A., Dutton, J. R., Tolar, J., OBrien, T. D Tags: Tissue Engineering and Regenerative Medicine, Pluripotent Stem Cells Source Type: research
