Treatment of Crohn's-Related Rectovaginal Fistula With Allogeneic Expanded-Adipose Derived Stem Cells: A Phase I-IIa Clinical Trial
The aim of this clinical trial was to determine the safety and feasibility of expanded allogeneic adipose-derived stem cells to treat Crohn’s-related rectovaginal fistula (CRRVF). We designed a phase I–II clinical trial (https://ClinicalTrials.gov, NCT00999115) to treat 10 patients with CRRVF. Patients receiving biological therapy during follow-up were excluded. Curettage was performed, and a vaginal or rectal flap was added if the surgeon considered it necessary. The therapeutic protocol included intralesional injection of 20 million stem cells in the vaginal walls (submucosal area) and fistula tract. Healing ...
Source: Stem Cells Translational Medicine - October 18, 2016 Category: Stem Cells Authors: Garcia-Arranz, M., Herreros, M. D., Gonzalez-Gomez, C., de la Quintana, P., Guadalajara, H., Georgiev-Hristov, T., Trebol, J., Garcia-Olmo, D. Tags: Adipose-Derived Stem Cells, Human Clinical Articles Source Type: research
Umbilical Cord-Derived Mesenchymal Stem Cell-Derived Exosomal MicroRNAs Suppress Myofibroblast Differentiation by Inhibiting the Transforming Growth Factor-{beta}/SMAD2 Pathway During Wound Healing
Excessive scar formation caused by myofibroblast aggregations is of great clinical importance during skin wound healing. Studies have shown that mesenchymal stem cells (MSCs) can promote skin regeneration, but whether MSCs contribute to scar formation remains undefined. We found that umbilical cord-derived MSCs (uMSCs) reduced scar formation and myofibroblast accumulation in a skin-defect mouse model. We found that these functions were mainly dependent on uMSC-derived exosomes (uMSC-Exos) and especially exosomal microRNAs. Through high-throughput RNA sequencing and functional analysis, we demonstrated that a group of uMSC-...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Fang, S., Xu, C., Zhang, Y., Xue, C., Yang, C., Bi, H., Qian, X., Wu, M., Ji, K., Zhao, Y., Wang, Y., Liu, H., Xing, X. Tags: Tissue Engineering and Regenerative Medicine, Cord Blood Stem Cells, Mesenchymal Stem Cells Source Type: research
Multifaceted Therapeutic Benefits of Factors Derived From Dental Pulp Stem Cells for Mouse Liver Fibrosis
This study demonstrated that a single intravenous administration of stem cells from human exfoliated deciduous teeth (SHEDs) or of the serum-free conditioned medium (CM) derived from SHEDs markedly improved mouse liver fibrosis (LF). SHED-CM suppressed chronic inflammation, eliminated activated hepatic stellate cells by inducing their apoptosis, protected hepatocytes from undergoing apoptosis, and induced differentiation of tissue-repairing macrophages expressing high levels of the profibrinolytic factor matrix metalloproteinase 13. Furthermore, hepatocyte growth factor played a central role in the SHED-CM-mediated resolut...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Hirata, M., Ishigami, M., Matsushita, Y., Ito, T., Hattori, H., Hibi, H., Goto, H., Ueda, M., Yamamoto, A. Tags: Tissue Engineering and Regenerative Medicine, Mesenchymal Stem Cells Source Type: research
MicroRNA-146b, a Sensitive Indicator of Mesenchymal Stem Cell Repair of Acute Renal Injury
In conclusion, elevated miR-146b expression contributes to cisplatin-induced AKI, partly through ErbB4 downregulation. miR-146b might be an early biomarker for AKI, and miR-146b inhibition could be a novel strategy for AKI treatment.
Significance
The present study found that microRNA-146b (miR-146b) might be a novel biomarker for acute kidney injury and an indicator for its recovery after treatment with mesenchymal stem cells (MSCs). The results showed that in acute kidney injury induced by cisplatin, miR-146b in serum increased more quickly than did the usual indexes of kidney injury and decreased with restoration of MSC...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Zhu, Y., Yu, J., Yin, L., Zhou, Y., Sun, Z., Jia, H., Tao, Y., Liu, W., Zhang, B., Zhang, J., Wang, M., Zhang, X., Yan, Y., Xue, J., Gu, H., Mao, F., Xu, W., Qian, H. Tags: Tissue Engineering and Regenerative Medicine, Adult Stem Cells, Mesenchymal Stem Cells Source Type: research
High-Efficiency Serum-Free Feeder-Free Erythroid Differentiation of Human Pluripotent Stem Cells Using Small Molecules
This article describes a good manufacturing practice (GMP)-compatible, feeder-free and serum-free method to produce large numbers of erythroid cells from human pluripotent stem cells (hPSCs), either embryonic or induced. This multistep protocol combines cytokines and small molecules to mimic and surpass the early stages of development. It produces, without any selection or sorting step, a population of cells in which 91.8% ± 5.4% express CD34 at day 7, 98.6% ± 1.3% express CD43 at day 10, and 99.1% ± 0.95% of cells are CD235a positive by day 31 of the differentiation process. Moreover, this differentia...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Olivier, E. N., Marenah, L., McCahill, A., Condie, A., Cowan, S., Mountford, J. C. Tags: Tissue Engineering and Regenerative Medicine, Embryo Development Source Type: research
Externally Applied Static Magnetic Field Enhances Cardiac Retention and Functional Benefit of Magnetically Iron-Labeled Adipose-Derived Stem Cells in Infarcted Hearts
Although adipose-derived stem cells (ASCs) hold the promise of effective therapy for myocardial infarction, low cardiac retention of implanted ASCs has hindered their therapeutic efficiency. We investigated whether an externally applied static magnetic field (SMF) enhances cardiac localization of "magnetic" cells and promotes heart function recovery when ASCs are preloaded with superparamagnetic iron oxide (SPIO) nanoparticles. The influence of SMF (0.1 Tesla) on the biological activities of SPIO-labeled ASCs (SPIOASCs) was investigated first. Fifty-six female rats with myocardial infarction underwent intramyocardial injec...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Wang, J., Xiang, B., Deng, J., Lin, H.-Y., Zheng, D., Freed, D. H., Arora, R. C., Tian, G. Tags: Tissue Engineering and Regenerative Medicine, Adipose-Derived Stem Cells Source Type: research
Closure of a Recurrent Bronchopleural Fistula Using a Matrix Seeded With Patient-Derived Mesenchymal Stem Cells
We describe the first-in-human application of an autologous mesenchymal stem cell (MSC)-seeded matrix graft to repair a multiply recurrent postpneumonectomy BPF. Adipose-derived MSCs were isolated from patient abdominal adipose tissue, expanded, and seeded onto bio-absorbable mesh, which was surgically implanted at the site of BPF. Clinical follow-up and postprocedural radiological and bronchoscopic imaging were performed to ensure BPF closure, and in vitro stemness characterization of patient-specific MSCs was performed. The patient remained clinically asymptomatic without evidence of recurrence on bronchoscopy at 3 month...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Aho, J. M., Dietz, A. B., Radel, D. J., Butler, G. W., Thomas, M., Nelson, T. J., Carlsen, B. T., Cassivi, S. D., Resch, Z. T., Faubion, W. A., Wigle, D. A. Tags: Tissue Engineering and Regenerative Medicine, Adipose-Derived Stem Cells Source Type: research
Bone Regeneration Using the Freshly Isolated Autologous Stromal Vascular Fraction of Adipose Tissue in Combination With Calcium Phosphate Ceramics
This study demonstrated for the first time the feasibility, safety, and potential efficacy of SVF seeded on bone substitutes for MSFE, providing the first step toward a novel treatment concept that might offer broad potential for SVF-based regenerative medicine applications.
Significance
This is the first-in-human study using freshly isolated, autologous adipose stem cell preparations (the stromal vascular fraction [SVF] of adipose tissue) applied in a one-step surgical procedure with calcium phosphate ceramics (CaP) to increase maxillary bone height for dental implantations. All 10 patients received CaP plus SVF on one s...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Prins, H.-J., Schulten, E. A. J. M., ten Bruggenkate, C. M., Klein-Nulend, J., Helder, M. N. Tags: Tissue Engineering and Regenerative Medicine, Adult Stem Cells, Mesenchymal Stem Cells, Adipose-Derived Stem Cells Source Type: research
First Proposal of Minimum Information About a Cellular Assay for Regenerative Medicine
This study, which is the fruit of collaborative work by scientists at stem cell banks and cellular information registries worldwide, including those in the U.S., the U.K., Europe, and Japan, proposes new minimum information guidelines, Minimum Information About a Cellular Assay for Regenerative Medicine (MIACARM), for cellular assay data deposition. MIACARM is intended to promote data exchange and facilitation of practical regenerative medicine. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Sakurai, K., Kurtz, A., Stacey, G., Sheldon, M., Fujibuchi, W. Tags: Mesenchymal Stem Cells, Standards, Policies, Protocols, and Regulations for Cell-Based Therapies Source Type: research
Concise Review: Markers for Assessing Human Stem Cell-Derived Implants as {beta}-Cell Replacement in Type 1 Diabetes
This study proposes the combined use of in vitro, in vivo, and ex vivo markers to assess this potential in preclinical models and in clinical studies. (Source: Stem Cells Translational Medicine)
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Pipeleers, D., Robert, T., De Mesmaeker, I., Ling, Z. Tags: Embryonic Stem Cells, Pluripotent Stem Cells, Pancreas, Enabling Technologies for Cell-Based Clinical Translation Source Type: research
Concise Review: Recent Advances in the In Vitro Derivation of Blood Cell Populations
Hematopoietic cell-based therapies are currently available treatment options for many hematological and nonhematological disorders. However, the scarcity of allogeneic donor-derived cells is a major hurdle in treating these disorders. Embryonic stem cell-based directed differentiation and direct reprogramming of somatic cells provide excellent tools for the potential generation of hematopoietic stem cells usable in the clinic for cellular therapies. In addition to blood stem cell transplantation, mature blood cells such as red blood cells, platelets, and engineered T cells have also been increasingly used to treat several ...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Batta, K., Menegatti, S., Garcia-Alegria, E., Florkowska, M., Lacaud, G., Kouskoff, V. Tags: Concise Review, Embryonic Stem Cells, Hematopoietic Stem Cells, Tissue-Specific Progenitor and Stem Cells Source Type: research
PTEN Promotes Dopaminergic Neuronal Differentiation Through Regulation of ERK-Dependent Inhibition of S6K Signaling in Human Neural Stem Cells
This article adds to the body of knowledge about the mechanism of extracellular signal-regulated kinase (ERK)-mediated differentiation by describing the molecular function of phosphatase and tension homolog (PTEN) during the neuronal differentiation of human neural stem cells (hNSCs). Previous studies showed that S6K signaling promoted neuronal differentiation in hNSCs via the phosphatidylinositol 3-kinase Akt-mammalian target of rapamycin signaling pathway. A further series of studies investigated whether this S6 kinase-induced differentiation in hNSCs involves regulation of ERK signaling by PTEN. The current study identi...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Lee, J. E., Lim, M. S., Park, J. H., Park, C. H., Koh, H. C. Tags: Embryonic Stem Cells, Neural/Progenitor Stem Cells, Tissue-Specific Progenitor and Stem Cells Source Type: research
Hepatocyte Growth Factor Is Required for Mesenchymal Stromal Cell Protection Against Bleomycin-Induced Pulmonary Fibrosis
The incidence of idiopathic pulmonary fibrosis is on the rise and existing treatments have failed to halt or reverse disease progression. Mesenchymal stromal cells (MSCs) have potent cytoprotective effects, can promote tissue repair, and have demonstrated efficacy in a range of fibrotic lung diseases; however, the exact mechanisms of action remain to be elucidated. Chemical antagonists and short hairpin RNA knockdown were used to identify the mechanisms of action used by MSCs in promoting wound healing, proliferation, and inhibiting apoptosis. Using the bleomycin induced fibrosis model, the protective effects of early or l...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Cahill, E. F., Kennelly, H., Carty, F., Mahon, B. P., English, K. Tags: Mesenchymal Stem Cells, Tissue-Specific Progenitor and Stem Cells Source Type: research
Concise Review: Functional Definition of Endothelial Progenitor Cells: A Molecular Perspective
Since the discovery of endothelial progenitor cells (EPCs) almost 2 decades ago, there has been great hope in their use in treating chronic ischemic disease. Unfortunately, to date, many of the clinical trials using EPCs have been hampered by the lack of clear definition of this cell population. Attributes of a progenitor population are self-renewal and multipotentiality. Major progress has been achieved moving from a definition of EPCs based on a candidate cell surface molecule to a functional definition based essentially on self-renewal hierarchy of endothelial colony-forming cells (ECFCs). More recent work has seized on...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Patel, J., Donovan, P., Khosrotehrani, K. Tags: Cord Blood Stem Cells, Placenta-Derived Stem Cells, Tissue-Specific Progenitor and Stem Cells Source Type: research
Impact of Feeding Strategies on the Scalable Expansion of Human Pluripotent Stem Cells in Single-Use Stirred Tank Bioreactors
This study paves the way toward more efficient GMP-compliant cell production and underscores the enormous process development potential of hPSCs in suspension culture.
Significance
Human pluripotent stem cells (hPSCs) are a unique source for the, in principle, unlimited production of functional human cell types in vitro, which are of high value for therapeutic and industrial applications. This study applied single-use, clinically compliant bioreactor technology to develop advanced, matrix-free, and more efficient culture conditions for the mass production of hPSCs in scalable suspension culture. Using extensive analytical...
Source: Stem Cells Translational Medicine - September 20, 2016 Category: Stem Cells Authors: Kropp, C., Kempf, H., Halloin, C., Robles-Diaz, D., Franke, A., Scheper, T., Kinast, K., Knorpp, T., Joos, T. O., Haverich, A., Martin, U., Zweigerdt, R., Olmer, R. Tags: Embryo Development, Pluripotent Stem Cells Source Type: research
