Human Cardiomyocytes Prior to Birth by Integration-Free Reprogramming of Amniotic Fluid Cells
This study presents transgene-free human amniotic fluid-derived cardiomyocytes (AF-CMs) for potential therapy in tissue engineering and regenerative medicine applications. Using 8–10 ml of amniotic fluid harvested at 20 weeks gestation from normal pregnancies, a mixed population of atrial, ventricular, and nodal AF-CMs were reliably generated after Sendai virus reprogramming toward pluripotency. Functional characterization of purified populations of beating AF-CMs revealed normal calcium transients and appropriate chronotropic responses after β-adrenergic agonist stimulation in comparison with dermal fibroblast ...
Source: Stem Cells Translational Medicine - November 16, 2016 Category: Stem Cells Authors: Jiang, G., Herron, T. J., Di Bernardo, J., Walker, K. A., OShea, K. S., Kunisaki, S. M. Tags: Amniotic Stem Cells, Cardiac Stem Cells, Pluripotent Stem Cells, Mesenchymal Stem Cells, Fetal and Neonatal Stem Cells, Skin-Derived Precursors/Progenitors Source Type: research
Concise Review: In Vitro Formation of Bone-Like Nodules Sheds Light on the Application of Stem Cells for Bone Regeneration
This article also highlights the limitations of current translational applications of stem cells and opportunities to use the bone-like nodule model for bone regenerative therapies.
Significance
Harnessing the differentiation of stem cells into bone-forming cells represents an intriguing avenue for the creation of functional skeletal tissues. Therefore, a profound understanding of bone development and morphogenesis sheds light on the regenerative application of stem cells in orthopedics and dentistry. In this concise review, studies deciphering the mechanisms that govern osteoblast commitment and differentiation are summa...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Mechiche Alami, S., Gangloff, S. C., Laurent-Maquin, D., Wang, Y., Kerdjoudj, H. Tags: Concise Review, Tissue Engineering and Regenerative Medicine, Mesenchymal Stem Cells Source Type: research
Epidermal Growth Factor Tethered to {beta}-Tricalcium Phosphate Bone Scaffolds via a High-Affinity Binding Peptide Enhances Survival of Human Mesenchymal Stem Cells/Multipotent Stromal Cells in an Immune-Competent Parafascial Implantation Assay in Mice
This report elucidates a method to tether EGF to bone induction material to improve the survival of mesenchymal stem cells/multipotent stromal cells in vivo. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Nuschke, A., Rodrigues, M., Rivera, J., Yates, C., Whaley, D., Stolz, D., Griffith, L., Wells, A. Tags: Tissue Engineering and Regenerative Medicine, Mesenchymal Stem Cells Source Type: research
A Simple Method to Determine the Purity of Adipose-Derived Stem Cell-Based Cell Therapies
It is important to standardize methods to quantify the purity of adipose tissue-derived cells for regenerative medicine. We developed a simple and robust tool to discriminate fibroblasts and adipose stem cells (ASCs) by testing release of specific growth factors. ASCs and dermal fibroblasts (DFs) were isolated from human donors (n = 8). At passage 4, cultures were prepared with progressive ASC/DF ratios of 100%/0%, 75%/25%, 50%/50%, 25%/75%, and 0%/100% for each donor and incubated in hypoxic chambers at 0.1% and 5% O2 and hyperglycemia at 1.0 and 4.5 g/l. After incubation for 24 hours, cell survival, proliferation, and gr...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Dufrane, D., Lafosse, A. Tags: Adipose-Derived Stem Cells, Standards, Policies, Protocols, and Regulations for Cell-Based Therapies Source Type: research
In Pursuit of Authenticity: Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium for Clinical Applications
This study provides a reference dataset to authenticate genetically diverse iPSC-RPE derived for clinical applications.
Significance
The retinal pigment epithelium (RPE) is essential for maintaining visual function. RPE derived from human induced pluripotent stem cells (iPSC-RPE) offer a promising cell-based transplantation therapy for slowing or rescuing RPE-induced visual function loss. For effective treatment, iPSC-RPE must recapitulate the physiology of native human RPE. A set of physiologically relevant functional assays are provided that assess the polarized functional activity and maturation state of the intact RPE...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Miyagishima, K. J., Wan, Q., Corneo, B., Sharma, R., Lotfi, M. R., Boles, N. C., Hua, F., Maminishkis, A., Zhang, C., Blenkinsop, T., Khristov, V., Jha, B. S., Memon, O. S., DSouza, S., Temple, S., Miller, S. S., Bharti, K. Tags: Pluripotent Stem Cells, Standards, Policies, Protocols, and Regulations for Cell-Based Therapies Source Type: research
Survival and Functionality of Human Induced Pluripotent Stem Cell-Derived Oligodendrocytes in a Nonhuman Primate Model for Multiple Sclerosis
This study demonstrates for the first time that human induced pluripotent stem cell (iPSC)-derived oligodendrocyte precursor cells (OPCs), after intracortical implantation in a nonhuman primate model for progressive multiple sclerosis (MS), migrate to the lesions and remyelinate denuded axons. These findings imply that human iPSC-OPCs can be a therapeutic tool for MS. The results of this feasibility study on the potential use of hiPSC-derived OPCs are of great importance for all MS researchers focusing on the stimulation of remyelination in MS patients. Further optimization and research on practical issues related to the s...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Thiruvalluvan, A., Czepiel, M., Kap, Y. A., Mantingh-Otter, I., Vainchtein, I., Kuipers, J., Bijlard, M., Baron, W., Giepmans, B., Bruck, W., t Hart, B. A., Boddeke, E., Copray, S. Tags: Pluripotent Stem Cells, Oligodendrocytes Precursor Cells, Enabling Technologies for Cell-Based Clinical Translation Source Type: research
Mesenchymal Stem Cells Modulate the Functional Properties of Microglia via TGF-{beta} Secretion
In this study, we aimed to clarify the role of TGF-β that is involved in MSC effectiveness, especially focusing on microglia functional properties that play a pivotal role in neuroinflammation. We found that MSC-conditioned media (MSC-CM) inhibited proinflammatory cytokine expression, restored alternative activated microglia phenotype markers (fractalkine receptor, mannose receptor, CD200 receptor), and enhanced phagocytosis in lipopolysaccharide (LPS)-stimulated microglia. In addition, TGF-β in MSC-CM played a major role in these effects by inhibiting the nuclear factor-B pathway and restoring the TGF-β pat...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Noh, M. Y., Lim, S. M., Oh, K.-W., Cho, K.-A., Park, J., Kim, K.-S., Lee, S.-J., Kwon, M.-S., Kim, S. H. Tags: Mesenchymal Stem Cells, Enabling Technologies for Cell-Based Clinical Translation Source Type: research
V-Maf Musculoaponeurotic Fibrosarcoma Oncogene Homolog A Synthetic Modified mRNA Drives Reprogramming of Human Pancreatic Duct-Derived Cells Into Insulin-Secreting Cells
This study shows an innovative and robust in vitro system for large-scale production of β-like cells from human pancreatic duct-derived cells (HDDCs) using a nonintegrative RNA-based reprogramming technique. V-Maf musculoaponeurotic fibrosarcoma oncogene homolog A overexpression was efficient and sufficient to induce β-cell differentiation and insulin secretion from HDDCs in response to glucose stimulation, allowing the cells to mitigate hyperglycemia in diabetic SCID-beige mice. The data describe a new, reliable, and fast procedure in adult human pancreatic cells to generate clinically relevant amounts of new &b...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Corritore, E., Lee, Y.-S., Pasquale, V., Liberati, D., Hsu, M.-J., Lombard, C. A., Van Der Smissen, P., Vetere, A., Bonner-Weir, S., Piemonti, L., Sokal, E., Lysy, P. A. Tags: Adult Stem Cells, Pancreas, Enabling Technologies for Cell-Based Clinical Translation Source Type: research
Adult Human Peripheral Blood Mononuclear Cells Are Capable of Producing Neurocyte or Photoreceptor-Like Cells That Survive in Mouse Eyes After Preinduction With Neonatal Retina
This study provides support for the use of peripheral blood mononuclear cells (PBMCs) as a potential source of pluripotent stem cells for treating retinal degeneration. First, this study demonstrated that PBMCs can differentiate into retinal neuron-like cells in vitro and in vivo. Second, some transplanted cells expressed markers for neural progenitors, mature neurons, or photoreceptors at 1, 3, and 6 months after subretinal injection. Finally, this study showed that PBMC transplantation can improve the function of a degenerated retina. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Xian, B., Zhang, Y., Peng, Y., Huang, J., Li, W., Wang, W., Zhang, M., Li, K., Zhang, H., Zhao, M., Liu, X., Huang, B. Tags: Adult Stem Cells, Pluripotent Stem Cells, Enabling Technologies for Cell-Based Clinical Translation Source Type: research
Human Mesenchymal Stem Cells Impact Th17 and Th1 Responses Through a Prostaglandin E2 and Myeloid-Dependent Mechanism
Human mesenchymal stem cells (hMSCs) are being increasingly pursued as potential therapies for immune-mediated conditions, including multiple sclerosis. Although they can suppress human Th1 responses, they reportedly can reciprocally enhance human Th17 responses. Here, we investigated the mechanisms underlying the capacity of hMSCs to modulate human Th1 and Th17 responses. Human adult bone marrow-derived MSCs were isolated, and their purity and differentiation capacity were confirmed. Human venous peripheral blood mononuclear cells (PBMC) were activated, alone, together with hMSC, or in the presence of hMSC-derived superna...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Rozenberg, A., Rezk, A., Boivin, M.-N., Darlington, P. J., Nyirenda, M., Li, R., Jalili, F., Winer, R., Artsy, E. A., Uccelli, A., Reese, J. S., Planchon, S. M., Cohen, J. A., Bar-Or, A. Tags: Mesenchymal Stem Cells, Cell-Based Drug Development, Screening, and Toxicology Source Type: research
Autophagy Improves the Immunosuppression of CD4+ T Cells by Mesenchymal Stem Cells Through Transforming Growth Factor-{beta}1
This study makes a significant contribution to demonstrate that autophagy could improve the immunosuppression of CD4+ T cells by mesenchymal stem cells through transforming growth factor-β1. Therefore, regulation of autophagy in MSCs would provide a promising strategy to improve the therapeutic efficacy of these cells. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Gao, L., Cen, S., Wang, P., Xie, Z., Liu, Z., Deng, W., Su, H., Wu, X., Wang, S., Li, J., Ouyang, Y., Wu, Y., Shen, H. Tags: Mesenchymal Stem Cells, Cell-Based Drug Development, Screening, and Toxicology Source Type: research
Type 1 Diabetes Mellitus Donor Mesenchymal Stromal Cells Exhibit Comparable Potency to Healthy Controls In Vitro
In this study, we used gene array in combination with functional in vitro assays to address these questions. MSCs from T1D donors and healthy controls were expanded from BM aspirates. BM mononuclear cell counts and growth kinetics were comparable between the groups, with equivalent colony-forming unit-fibroblast capacity. Gene microarrays demonstrated differential gene expression between healthy and late-stage T1D donors in relation to cytokine secretion, immunomodulatory activity, and wound healing potential. Despite transcriptional differences, T1D MSCs did not demonstrate a significant difference from healthy controls i...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Davies, L. C., Alm, J. J., Heldring, N., Moll, G., Gavin, C., Batsis, I., Qian, H., Sigvardsson, M., Nilsson, B., Kyllonen, L. E., Salmela, K. T., Carlsson, P.-O., Korsgren, O., Le Blanc, K. Tags: Adult Stem Cells, Mesenchymal Stem Cells, Tissue-Specific Progenitor and Stem Cells Source Type: research
Antifibrotic Activity of Human Placental Amnion Membrane-Derived CD34+ Mesenchymal Stem/Progenitor Cell Transplantation in Mice With Thioacetamide-Induced Liver Injury
This study aimed to evaluate the therapeutic effect of MSC-based cell transplantation as an alternative treatment for liver fibrosis. A CD34-positive subpopulation of human placental amnion membrane-derived stem/progenitor cells (CD34+ AMSPCs) was isolated through the depletion of CD34-negative stromal fibroblasts (CD34– AMSFCs) facilitated by CD34 fluorescence-activated cell sorting, enriched and expanded ex vivo. These cells express pluripotency markers and demonstrate multidirectional differentiation potentials. Comparative analysis was made between CD34+ AMSPCs and CD34– AMSFCs in terms of the expressions o...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Lee, P.-H., Tu, C.-T., Hsiao, C.-C., Tsai, M.-S., Ho, C.-M., Cheng, N.-C., Hung, T.-M., Shih, D. T.-b. Tags: Amniotic Stem Cells, Mesenchymal Stem Cells, Tissue-Specific Progenitor and Stem Cells Source Type: research
A Novel Protocol for Directed Differentiation of C9orf72-Associated Human Induced Pluripotent Stem Cells Into Contractile Skeletal Myotubes
This study presents a rapid, efficient, and transgene-free method for generating multinucleated skeletal myotubes from iPSCs and a resource for further modeling the role of skeletal muscle in amyotrophic lateral sclerosis and other motor neuron diseases.
Significance
Protocols to produce skeletal myotubes for disease modeling or therapy are scarce and incomplete. The present study efficiently generates functional skeletal myotubes from human induced pluripotent stem cells using a small molecule-based approach. Using this strategy, terminal myogenic induction of up to 64% in 36 days and spontaneously contractile myotubes w...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Swartz, E. W., Baek, J., Pribadi, M., Wojta, K. J., Almeida, S., Karydas, A., Gao, F.-B., Miller, B. L., Coppola, G. Tags: Pluripotent Stem Cells, Pluripotent Stem Cells, Muscle Stem Cells Source Type: research
Human Induced Pluripotent Stem Cells Differentiate Into Functional Mesenchymal Stem Cells and Repair Bone Defects
In conclusion, MSCs can be derived from iPSCs and exhibit self-renewal without tumorigenic ability. Compared with BM-MSCs, aiMSCs acquire more of a stem cell phenotype, whereas tiMSCs acquire more of a differentiated osteoblast phenotype, which aids bone regeneration but does not allow the cells to induce ectopic bone formation (even when triggered by bone morphogenetic proteins), unless in an orthotopic site of bone fracture.
Significance
Mesenchymal stem cells (MSCs) are currently the most established cells for skeletal tissue engineering and regeneration of various skeletal conditions; however, availability of autologo...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Sheyn, D., Ben-David, S., Shapiro, G., De Mel, S., Bez, M., Ornelas, L., Sahabian, A., Sareen, D., Da, X., Pelled, G., Tawackoli, W., Liu, Z., Gazit, D., Gazit, Z. Tags: Pluripotent Stem Cells, Pluripotent Stem Cells, Mesenchymal Stem Cells Source Type: research
