Stem cells translational medicine
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Stem Cells Transl Med · Oct 2020
ReviewCurrent status of mesenchymal stem cell therapy for immune/inflammatory lung disorders: Gleaning insights for possible use in COVID-19.
The broad immunomodulatory properties of human mesenchymal stem cells (MSCs) have allowed for wide application in regenerative medicine as well as immune/inflammatory diseases, including unmatched allogeneic use. The novel coronavirus disease COVID-19 has unleashed a pandemic in record time accompanied by an alarming mortality rate mainly due to pulmonary injury and acute respiratory distress syndrome. Because there are no effective preventive or curative therapies currently, MSC therapy (MSCT) has emerged as a possible candidate despite the lack of preclinical data of MSCs for COVID-19. ⋯ Since these first reports, preclinical data showing beneficial effects of MSC immunomodulation have accumulated substantially, and as a consequence, over a third of MSCT clinical trials now target immune/inflammatory diseases. There is much preclinical evidence for MSCT in noninfectious-including chronic obstructive pulmonary disease, asthma, and idiopathic pulmonary fibrosis-as well as infectious bacterial immune/inflammatory lung disorders, with data generally demonstrating therapeutic effects; however, for infectious viral pulmonary conditions, the preclinical evidence is more scarce with some inconsistent outcomes. In this article, we review the mechanistic evidence for clinical use of MSCs in pulmonary immune/inflammatory disorders, and survey the ongoing clinical trials-including for COVID-19-of MSCT for these diseases, with some perspectives and comment on MSCT for COVID-19.
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Stem Cells Transl Med · Sep 2020
Meta AnalysisCell-based therapy to reduce mortality from COVID-19: Systematic review and meta-analysis of human studies on acute respiratory distress syndrome.
Severe cases of COVID-19 infection, often leading to death, have been associated with variants of acute respiratory distress syndrome (ARDS). Cell therapy with mesenchymal stromal cells (MSCs) is a potential treatment for COVID-19 ARDS based on preclinical and clinical studies supporting the concept that MSCs modulate the inflammatory and remodeling processes and restore alveolo-capillary barriers. The authors performed a systematic literature review and random-effects meta-analysis to determine the potential value of MSC therapy for treating COVID-19-infected patients with ARDS. ⋯ No related serious adverse events were reported and mild adverse events resolved spontaneously. A trend was found of improved radiographic findings, pulmonary function (lung compliance, tidal volumes, PaO2 /FiO2 ratio, alveolo-capillary injury), and inflammatory biomarker levels. No comparisons were made between MSCs of different sources.
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Stem Cells Transl Med · Aug 2019
Bone Marrow Mesenchymal Stromal Cell Treatment in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation.
Patients with late-stage Kellgren-Lawrence knee osteoarthritis received a single intra-articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells (BM-MSCs) in a phase I/IIa trial to assess safety and efficacy using a broad toolset of analytical methods. Besides safety, outcomes included patient-reported outcome measures (PROMs): Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); contrast-enhanced magnetic resonance imaging (MRI) for cartilage morphology (Whole Organ MRI Scores [WORMS]), collagen content (T2 scores), and synovitis; and inflammation and cartilage turnover biomarkers, all over 12 months. BM-MSCs were characterized by a panel of anti-inflammatory markers to predict clinical efficacy. ⋯ Autologous BM-MSCs are safe and result in significant improvements in PROMs at 12 months. Our analytical tools provide important insights into BM-MSC dosing and BM-MSC reduction of synovial inflammation and cartilage degradation and provide a highly predictive donor selection criterion that will be critical in translating MSC therapy for osteoarthritis. Stem Cells Translational Medicine 2019;8:746&757.
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Stem Cells Transl Med · Jun 2019
Randomized Controlled TrialIntra-Articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo-Controlled Clinical Trial.
Mesenchymal stem cells (MSCs) have been the focus of an emerging treatment for osteoarthritis. However, few studies reported about outcomes of an intra-articular injection of autologous adipose-derived mesenchymal stem cells (AD-MSCs). This study aimed to assess the efficacy and safety of a single intra-articular injection of AD-MSCs for patients with knee osteoarthritis. ⋯ An intra-articular injection of autologous AD-MSCs provided satisfactory functional improvement and pain relief for patients with knee osteoarthritis in the outpatient setting, without causing adverse events at 6 months' follow-up. Larger sample size and long-term follow-up are required. Stem Cells Translational Medicine 2019;8:504-511.
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Stem Cells Transl Med · Mar 2019
Randomized Controlled TrialUmbilical Cord-Derived Mesenchymal Stromal Cells (MSCs) for Knee Osteoarthritis: Repeated MSC Dosing Is Superior to a Single MSC Dose and to Hyaluronic Acid in a Controlled Randomized Phase I/II Trial.
Knee osteoarthritis (OA) is a leading cause of pain and disability. Although conventional treatments show modest benefits, pilot and phase I/II trials with bone marrow (BM) and adipose-derived (AD) mesenchymal stromal cells (MSCs) point to the feasibility, safety, and occurrence of clinical and structural improvement in focal or diffuse disease. This study aimed to assess the safety and efficacy of the intra-articular injection of single or repeated umbilical cord-derived (UC) MSCs in knee OA. ⋯ No differences in MRI scores were detected. In a phase I/II trial (NCT02580695), repeated UC-MSC treatment is safe and superior to active comparator in knee OA at 1-year follow-up. Stem Cells Translational Medicine 2019;8:215&224.