Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease—a meta-analysis

Morata-Tarifa, Cynthia; Macías-Sánchez, María Del Mar; Gutiérrez‐Pizarraya, Antonio; Sánchez‐Pernaute, Rosario

doi:10.1186/s13287-020-01592-z

Cited by 43 publications

(50 citation statements)

References 48 publications

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“…Additionally, acute graft-versus-host-disease (GVHD) is a lifethreatening complication of allogeneic hematopoietic stem cell transplantation due to its inflammatory storm. A meta-analysis revealed that infused MSCs could reduce acute GVHD grade and increase overall survival [16]. The therapeutic effects of MSCs on ALI/ARDS and GVHD with powerful inflammatory balance are solid proofs for the application of MSCs on other originated ALI/ARDS.…”

Section: Main Textmentioning

confidence: 99%

Mesenchymal stem cells as a potential therapy for COVID-19

et al. 2020

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The outbreak of 2019 novel coronavirus disease worldwide is becoming rapidly a major concern. The number of severe cases has increased dramatically worldwide, while specific treatment options are scarce. The main pathologic features of severe or critical COVID-19 were consistent with acute lung injure (ALI)/acute respiratory distress syndrome (ARDS), characterized by cellular fibromyxoid exudates, extensive pulmonary inflammation, pulmonary edema, and hyaline membrane formation. Mesenchymal stem cells (MSCs) can balance the inflammatory response and has been mentioned to be effective on ALI/ARDS from both infectious and noninfectious causes previously, presenting an important opportunity to be applied to COVID-19. In this commentary, we summarize the clinical trials of MSCs treatments on ALI/ARDS and raise MSCs as a hopefully alternative therapy for severe or critical COVID-19.

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Section: Main Textmentioning

confidence: 99%

Mesenchymal stem cells as a potential therapy for COVID-19

et al. 2020

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“…Prevention of GvHD (both acute and chronic) has been attempted by MSC infusion, generally given together with the HSC graft and in some cases with additional subsequent infusions up to 3 weeks following transplantation. These studies have been nicely reviewed recently by Morata-Tarifa et al, in a work which included the metaanalysis of 16 studies and a total of 654 patients (28). The data overall show a trend for a lower incidence of aGVHD, particularly grade IV and a reduced cGvHD, particularly extended cGvHD (see also below paragraph on cGvHD).…”

Section: Prophylaxis Of Agvhd With Mscsmentioning

confidence: 98%

“…MSCs for chronic GvHD prevention (28). The studies included 148 MSC treated patients and 236 controls, both adults and children.…”

Section: Mscs As Prophylaxis For Cgvhdmentioning

confidence: 99%

Tolerance to Bone Marrow Transplantation: Do Mesenchymal Stromal Cells Still Have a Future for Acute or Chronic GvHD?

Introna

Golay

2020

Front. Immunol.

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Mesenchymal Stromal Cells (MSCs) are fibroblast-like cells of mesodermal origin present in many tissues and which have the potential to differentiate to osteoblasts, adipocytes and chondroblasts. They also have a clear immunosuppressive and tissue regeneration potential. Indeed, the initial classification of MSCs as pluripotent stem cells, has turned into their identification as stromal progenitors. Due to the relatively simple procedures available to expand in vitro large numbers of GMP grade MSCs from a variety of different tissues, many clinical trials have tested their therapeutic potential in vivo. One pathological condition where MSCs have been quite extensively tested is steroid resistant (SR) graft versus host disease (GvHD), a devastating condition that may occur in acute or chronic form following allogeneic hematopoietic stem cell transplantation. The clinical and experimental results obtained have outlined a possible efficacy of MSCs, but unfortunately statistical significance in clinical studies has only rarely been reached and effects have been relatively limited in most cases. Nonetheless, the extremely complex pathogenetic mechanisms at the basis of GvHD, the fact that studies have been conducted often in patients who had been previously treated with multiple lines of therapy, the variable MSC doses and schedules administered in different trials, the lack of validated potency assays and clear biomarkers, the difference in MSC sources and production methods may have been major factors for this lack of clear efficacy in vivo. The heterogeneity of MSCs and their different stromal differentiation potential and biological activity may be better understood through more refined single cell sequencing and proteomic studies, where either an “anti-inflammatory” or a more “immunosuppressive” profile can be identified. We summarize the pathogenic mechanisms of acute and chronic GvHD and the role for MSCs. We suggest that systematic controlled clinical trials still need to be conducted in the most promising clinical settings, using better characterized cells and measuring efficacy with specific biomarkers, before strong conclusions can be drawn about the therapeutic potential of these cells in this context. The same analysis should be applied to other inflammatory, immune or degenerative diseases where MSCs may have a therapeutic potential.

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“…Given the current considerable safety and efficacy in pre-clinical and clinical studies, the roles of MSCs in regenerative medicine have attracted widespread attention, especially their immunomodulatory effects on autoimmune diseases and transplantions, such as Crohn's disease (CD) ( 9 ), rheumatoid arthritis (RA) ( 10 ), and systemic lupus erythematosus (SLE) ( 11 ), as well as graft-versus-host disease (GvHD) ( 12 ), kidney transplantation (KTx) ( 13 , 14 ), liver transplantation (LTx) ( 15 , 16 ), chronic lung allograft dysfunction (CLAD) ( 17 ) and small bowel transplantation (SBTx) ( 18 ), and even their roles in immune-mediated cell therapies ( 19 ). MSCs exhibit functional characteristics related to immune regulation and have consistently been shown to play roles in regulating innate and adaptive immune responses via a variety of pathways, such as cell-to-cell contact ( 20 ), soluble factors ( 21 ), and exosomes derived from MSCs ( 22 ).…”

Section: Introductionmentioning

confidence: 99%

The Immunomodulatory Effects of Mesenchymal Stem Cells on Regulatory B Cells

Liu

2020

Front. Immunol.

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The therapeutic potential of mesenchymal stem cells (MSCs) has been investigated in many preclinical and clinical studies. This potential is dominantly based on the immunosuppressive properties of MSCs. Although the therapeutic profiles of MSC transplantation are still not fully characterized, accumulating evidence has revealed that B cells change after MSC infusion, in particular inducing regulatory B cells (Bregs). The immunosuppressive effects of Bregs have been demonstrated, and these cells are being evaluated as new targets for the treatment of inflammatory diseases. MSCs are capable of educating B cells and inducing regulatory B cell production via cell-to-cell contact, soluble factors, and extracellular vesicles (EVs). These cells thus have the potential to complement each other's immunomodulatory functions, and a combined approach may enable synergistic effects for the treatment of immunological diseases. However, compared with investigations regarding other immune cells, investigations into how MSCs specifically regulate Bregs have been superficial and insufficient. In this review, we discuss the current findings related to the immunomodulatory effects of MSCs on regulatory B cells and provide optimal strategies for applications in immune-related disease treatments.

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Mesenchymal stromal cells for the prophylaxis and treatment of graft-versus-host disease—a meta-analysis

Cited by 43 publications

References 48 publications

Mesenchymal stem cells as a potential therapy for COVID-19

Mesenchymal stem cells as a potential therapy for COVID-19

Tolerance to Bone Marrow Transplantation: Do Mesenchymal Stromal Cells Still Have a Future for Acute or Chronic GvHD?

The Immunomodulatory Effects of Mesenchymal Stem Cells on Regulatory B Cells

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