Stem cells translational medicine
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Stem Cells Transl Med · Nov 2020
ReviewCell-based and antibody-mediated immunotherapies directed against leukemic stem cells in acute myeloid leukemia: Perspectives and open issues.
Despite new insights in molecular features of leukemic cells and the availability of novel treatment approaches and drugs, acute myeloid leukemia (AML) remains a major clinical challenge. In fact, many patients with AML relapse after standard therapy and eventually die from progressive disease. The basic concept of leukemic stem cells (LSC) has been coined with the goal to decipher clonal architectures in various leukemia-models and to develop curative drug therapies by eliminating LSC. ⋯ The current article provides a short overview of immunological targets expressed on LSC in AML. Moreover, cell-based therapies and immunotherapies tested in AML are discussed. Finally, the article provides an overview about LSC resistance and strategies to overcome resistance.
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Stem Cells Transl Med · Nov 2020
ReviewThe rationale of using mesenchymal stem cells in patients with COVID-19-related acute respiratory distress syndrome: What to expect.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused coronavirus disease 2019 (COVID-19) pandemic has become a global health crisis with an extremely rapid progress resulting in thousands of patients who may develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) treatment. So far, no specific antiviral therapeutic agent has been demonstrated to be effective for COVID-19; therefore, the clinical management is largely supportive and depends on the patients' immune response leading to a cytokine storm followed by lung edema, dysfunction of air exchange, and ARDS, which could lead to multiorgan failure and death. Given that human mesenchymal stem cells (MSCs) from various tissue sources have revealed successful clinical outcomes in many immunocompromised disorders by inhibiting the overactivation of the immune system and promoting endogenous repair by improving the microenvironment, there is a growing demand for MSC infusions in patients with COVID-19-related ARDS in the ICU. ⋯ Many centers have registered and approved, and some already started, single-case or phase I/II trials primarily aiming to rescue their critical patients when no other therapeutic approach responds. On the other hand, it is also very important to mention that there is a good deal of concern about clinics offering unproven stem cell treatments for COVID-19. The reviewers and oversight bodies will be looking for a balanced but critical appraisal of current trials.
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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 · 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.