Genetically Modified Mesenchymal Stromal/Stem Cells: Application in Critical Illness

Varkouhi, Amir K.; Monteiro, Ana Paula Teixeira; Tsoporis, James N.; Mei, Shirley H. J.; Stewart, Duncan J.; Santos, Claudia C. dos

doi:10.1007/s12015-020-10000-1

Cited by 34 publications

(18 citation statements)

References 156 publications

(165 reference statements)

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“…In this sense, the anti-inflammatory role of the MSC-derived EVs on T and B lymphocytes was observed regardless of the priming status of the MSCs used for their isolation. Whilst preclinical studies have demonstrated the therapeutic potential for MSC therapy in RA, optimization for their clinical use is an ongoing challenge and genetically engineered MSCs are being proposed to enhance their therapeutic potential [ 78 , 82 , 83 , 84 ].…”

Section: Preclinical Studiesmentioning

confidence: 99%

Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications

López‐Santalla

Fernandez-Perez

Garín

2020

Cells

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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects the lining of the synovial joints leading to stiffness, pain, inflammation, loss of mobility, and erosion of joints. Its pathogenesis is related to aberrant immune responses against the synovium. Dysfunction of innate and adaptive immunity, including dysregulated cytokine networks and immune complex-mediated complement activation, are involved in the progression of RA. At present, drug treatments, including corticosteroids, antirheumatic drugs, and biological agents, are used in order to modulate the altered immune responses. Chronic use of these drugs may cause adverse effects to a significant number of RA patients. Additionally, some RA patients are resistant to these therapies. In recent years, mesenchymal stem/stromal cell (MSCs)-based therapies have been largely proposed as a novel and promising stem cell therapeutic approach in the treatment of RA. MSCs are multipotent progenitor cells that have immunomodulatory properties and can be obtained and expanded easily. Today, nearly one hundred studies in preclinical models of RA have shown promising trends for clinical application. Proof-of-concept clinical studies have demonstrated satisfactory safety profile of MSC therapy in RA patients. The present review discusses MSC-based therapy approaches with a focus on published clinical data, as well as on clinical trials, for treatment of RA that are currently underway.

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Section: Preclinical Studiesmentioning

confidence: 99%

Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications

López‐Santalla

Fernandez-Perez

Garín

2020

Cells

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“…In viral vector delivery, insertional mutagenesis, immunogenicity, and limited carrying capacity are the main concerns. These concerns are minimal in nonviral delivery, which includes liposomes, plasmids, and miniplasmids; however, this approach has low transfection ability and transitory transgene expression ( 110 ). Due to MSC tropism in cancer tissues, several preclinical studies have investigated the possibility of using genetically engineered MSCs to target diverse types of cancer [ 111 – 113 ].…”

Section: Future Approaches To Enhancing Msc Potency For Covid-19 Treatmentmentioning

confidence: 99%

Mesenchymal stem cell-based therapy and exosomes in COVID-19: current trends and prospects

et al. 2021

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Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The virus causes an exaggerated immune response, resulting in a cytokine storm and acute respiratory distress syndrome, the leading cause of COVID-19-related mortality and morbidity. So far, no therapies have succeeded in circumventing the exacerbated immune response or cytokine storm associated with COVID-19. Mesenchymal stem cells (MSCs), through their immunomodulatory and regenerative activities, mostly mediated by their paracrine effect and extracellular vesicle production, have therapeutic potential in many autoimmune, inflammatory, and degenerative diseases. In this paper, we review clinical studies on the use of MSCs for COVID-19 treatment, including the salutary effects of MSCs on the pathophysiology of COVID-19 and the immunomodulation of the cytokine storm. Ongoing clinical trial designs, cell sources, dose and administration, and populations are summarized, and the paracrine mode of benefit is discussed. We also offer suggestions for optimizing MSC-based therapies, including genetic engineering, strategies for cell surface modification, nanotechnology applications, and combination therapies.

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“…Genetic engineering methods to modify MSCs can be classified as those using viral transduction, nonviral transfection, or genome editing tools and techniques to overexpress therapeutic proteins that complement their innate properties (Figure 3) [43][44][45][46]. A growing body of evidence indicates that the paracrine, homing, immunomodulatory, anti-inflammatory, and tissue repair properties of MSCs can be strengthened through genetic modification [47]. As therapeutic agents and novel carriers, genetically modified MSCs target metastasis and efficiently provide a local high concentration of therapeutic agents that target a specific disease (Table 1).…”

Section: Therapeutic Potential Of Mscsmentioning

confidence: 99%

Clinical applications of mesenchymal stromal cell-based therapies for pulmonary diseases: An Update and Concise Review

Chen¹,

Wang

Huang

et al. 2021

Int. J. Med. Sci.

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Lung disorders are a leading cause of morbidity and death worldwide. For many disease conditions, no effective and curative treatment options are available. Mesenchymal stromal cell (MSC)-based therapy is one of the cutting-edge topics in medical research today. It offers a novel and promising therapeutic option for various acute and chronic lung diseases due to its potent and broad-ranging immunomodulatory activities, bacterial clearance, tissue regeneration, and proangiogenic and antifibrotic properties, which rely on both cell-to-cell contact and paracrine mechanisms. This review covers the sources and therapeutic potential of MSCs. In particular, a total of 110 MSC-based clinical applications, either completed clinical trials with safety and early efficacy results reported or ongoing worldwide clinical trials of pulmonary diseases, are systematically summarized following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, including acute/viral pulmonary disease, community-acquired pneumonia (CAP), chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), interstitial lung diseases (ILD), chronic pulmonary fibrosis, bronchiolitis obliterans syndrome (BOS) and lung cancer. The results of recent clinical studies suggest that MSCs are a promising therapeutic approach for the treatment of lung diseases. Nevertheless, large-scale clinical trials and evaluation of long-term effects are necessary in further studies.

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Genetically Modified Mesenchymal Stromal/Stem Cells: Application in Critical Illness

Cited by 34 publications

References 156 publications

Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications

Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications

Mesenchymal stem cell-based therapy and exosomes in COVID-19: current trends and prospects

Clinical applications of mesenchymal stromal cell-based therapies for pulmonary diseases: An Update and Concise Review

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