Stem cells translational medicine
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Stem Cells Transl Med · Oct 2018
Genetic Modification of Mesenchymal Stem Cells Overexpressing Angiotensin II Type 2 Receptor Increases Cell Migration to Injured Lung in LPS-Induced Acute Lung Injury Mice.
Although mesenchymal stem cells (MSCs) transplantation has been shown to promote the lung respiration in acute lung injury (ALI) in vivo, its overall restorative capacity appears to be restricted mainly because of low retention in the injured lung. Angiotensin II (Ang II) are upregulated in the injured lung. Our previous study showed that Ang II increased MSCs migration via Ang II type 2 receptor (AT2R). ⋯ Thus, MSC-ShAT2R-injected group exhibited a significant increase of pulmonary vascular permeability and resulted in a deteriorative lung inflammation. Our results demonstrate that overexpression of AT2R enhance the migration of MSCs in ALI mice and may provide a new therapeutic strategy for ALI. Stem Cells Translational Medicine 2018;7:721-730.
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Stem Cells Transl Med · Sep 2018
Intravenous Infusion of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Rheumatoid Arthritis: A Phase Ia Clinical Trial.
Based on immunomodulatory actions of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), in vitro or preclinical studies of hUCB-MSCs have been conducted extensively in rheumatoid arthritis (RA). However, few human trials have investigated the outcomes of hUCB-MSC infusions. The CURE-iv trial was a phase I, uncontrolled, open label trial for RA patients with moderate disease activity despite treatment with methotrexate. ⋯ Reduced levels of IL-1β, IL-6, IL-8, and TNF-α at 24 hours were observed in the cluster infused with 1 × 108 MSCs. This phase Ia hUCB-MSC infusion trial for established RA patients revealed no short-term safety concerns. Stem Cells Translational Medicine 2018.
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Stem Cells Transl Med · Apr 2018
Delivery of Allogeneic Adipose Stem Cells in Polyethylene Glycol-Fibrin Hydrogels as an Adjunct to Meshed Autografts After Sharp Debridement of Deep Partial Thickness Burns.
Harvesting of autografts results in donor site morbidities and is limited in scenarios such as large total body surface area burns. In these instances, coverage is increased by meshing grafts at the expense of delayed biologic closure. Moreover, graft meshing increases the likelihood of contraction and hypertrophic scarring, limits range of motion, and worsens cosmesis. ⋯ The current study reports a dual-action adjunct therapy to autografting administered in situ, wherein FPEG acts as both scaffolding to prevent contraction, and as a delivery vehicle for ASCs to accelerate angiogenesis. This strategy may be used to incorporate other biologics for generating tissue engineered products aimed at improving wound healing and minimizing donor sites or scarring. Stem Cells Translational Medicine 2018;7:360-372.
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Stem Cells Transl Med · Jan 2018
A Universal Approach to Correct Various HBB Gene Mutations in Human Stem Cells for Gene Therapy of Beta-Thalassemia and Sickle Cell Disease.
Beta-thalassemia is one of the most common recessive genetic diseases, caused by mutations in the HBB gene. Over 200 different types of mutations in the HBB gene containing three exons have been identified in patients with β-thalassemia (β-thal) whereas a homozygous mutation in exon 1 causes sickle cell disease (SCD). Novel therapeutic strategies to permanently correct the HBB mutation in stem cells that are able to expand and differentiate into erythrocytes producing corrected HBB proteins are highly desirable. ⋯ We observed that HBB protein production was restored in erythrocytes derived from iPSCs of two patients. This strategy of restoring functional HBB gene expression will be able to correct most types of HBB gene mutations in β-thal and SCD. Stem Cells Translational Medicine 2018;7:87-97.
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Stem Cells Transl Med · Apr 2017
ReviewConcise Review: Mesenchymal Stromal Cell-Based Approaches for the Treatment of Acute Respiratory Distress and Sepsis Syndromes.
Despite extensive research on candidate pharmacological treatments and a significant and increasing prevalence, sepsis syndrome, and acute respiratory distress syndrome (ARDS) remain areas of unmet clinical need. Preclinical studies examining mesenchymal stromal cell (MSCs) based-therapies have provided compelling evidence of potential benefit; however, the precise mechanism by which MSCs exert a therapeutic influence, and whether MSC application is efficacious in humans, remains unknown. ⋯ The challenges of modeling such heterogeneous and rapidly progressive disease states are considered and we discuss how lessons from previous studies of pharmacological treatments for sepsis syndrome and ARDS might be used to inform and refine the design of the next generation of MSC clinical trials. Stem Cells Translational Medicine 2017;6:1141-1151.