Efficacy and safety of mesenchymal stromal cells for the prophylaxis of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials

Wang, Li; Zhu, Changjin; Ma, De-Xun; Gu, Zhenyang; Xu, Chang-Chun; Wang, Feiyan; Chen, Jigang; Liu, Chengjun; Guan, Li; Gao, Rui; Gao, Zhe; Fang, Shu; Zhuo, Du-Jun; Liu, Shu-Feng; Gao, Chunji

doi:10.1007/s00277-018-3384-8

Cited by 34 publications

(24 citation statements)

References 59 publications

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“…MSCs were infused at different time points from HSCT (within 24 h, at a median time of 28 days, or with multiple infusions at different time points). The analysis showed that infusion of MSCs significantly reduced the incidence of chronic GvHD (cGvHD) and there was a trend of longer overall survival in MSC-treated patients (33). Importantly, the meta-analysis on different sub-groups demonstrated that these favorable outcomes were significantly associated with late MSC administrations, thus supporting a more effective role of MSCs when licensed by a specific microenvironment developed after HSCT.…”

Section: A Brief History Of Mscsmentioning

confidence: 89%

“…After thousands of infusions, the most convincing conclusion is that MSCs are well-tolerated and safe for patients. Major infectious events, secondary neoplasms, or malignancy relapse do not seem to increase after MSC therapy (33,186). However, available data on MSC use in GvHD treatment represent the paradigm of the limitations of our current use of MSCs in most clinical applications.…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, MSCs were effective in reducing GvHD signs only when multiple infusions were administered after transplant but not when one single dose was co-infused with HSC transplantation (HSCT) (32). These experimental observations have been strongly supported by a meta-analysis recently performed by Wang and collaborators (33). In this work, the authors included 6 randomized clinical trials enrolling 365 patients.…”

Section: A Brief History Of Mscsmentioning

confidence: 96%

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Mesenchymal Stromal Cells for Graft Versus Host Disease: Mechanism-Based Biomarkers

et al. 2020

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Section: A Brief History Of Mscsmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Section: A Brief History Of Mscsmentioning

confidence: 96%

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Mesenchymal Stromal Cells for Graft Versus Host Disease: Mechanism-Based Biomarkers

et al. 2020

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“…Interestingly, analysis of a subset of CD4+ CD25+ CD127− regulatory T cells (Treg) and CD27+ memory B-lymphocytes was higher in the UC-MSC treated group although the proportion of total T cells and B cells remained unchanged. Wang et al [216] conducted a meta-analysis of 6 randomized controlled trials to evaluate the safety of MSC prophylaxis of cGVHD in 365 patients undergoing allo-HSCT. Beneficial prophylactic effects were seen with high dose UC-MSCs but not with low dose BM-MSCs.…”

Section: The Safety Of Msc Therapymentioning

confidence: 99%

Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients

et al. 2020

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In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, capital city of Hubei province in China. Cases of SARS-CoV-2 infection quickly grew by several thousand per day. Less than 100 days later, the World Health Organization declared that the rapidly spreading viral outbreak had become a global pandemic. Coronavirus disease 2019 (COVID-19) is typically associated with fever and respiratory symptoms. It often progresses to severe respiratory distress and multi-organ failure which carry a high mortality rate. Older patients or those with medical comorbidities are at greater risk for severe disease. Inflammation, pulmonary edema and an over-reactive immune response can lead to hypoxia, respiratory distress and lung damage. Mesenchymal stromal/stem cells (MSCs) possess potent and broad-ranging immunomodulatory activities. Multiple in vivo studies in animal models and ex vivo human lung models have demonstrated the MSC's impressive capacity to inhibit lung damage, reduce inflammation, dampen immune responses and aid with alveolar fluid clearance. Additionally, MSCs produce molecules that are antimicrobial and reduce pain. Upon administration by the intravenous route, the cells travel directly to the lungs where the majority are sequestered, a great benefit for the treatment of pulmonary disease. The in vivo safety of local and intravenous administration of MSCs has been demonstrated in multiple human clinical trials, including studies of acute respiratory distress syndrome (ARDS). Recently, the application of MSCs in the context of ongoing COVID-19 disease and other viral respiratory illnesses has demonstrated reduced patient mortality and, in some cases, improved long-term pulmonary function. Adipose-derived stem cells (ASC), an abundant type of MSC, are proposed as a therapeutic option for the treatment of COVID-19 in order to reduce morbidity and mortality. Additionally, when proven to be safe and effective, ASC treatments may reduce the demand on critical hospital resources. The ongoing COVID-19 outbreak has resulted in significant healthcare and socioeconomic burdens across the globe. There is a desperate need for safe and effective treatments. Cellular based therapies hold great promise for the treatment of COVID-19. This literature summary reviews the scientific rationale and need for clinical studies of adipose-derived stem cells and other types of mesenchymal stem cells in the treatment of patients who suffer with COVID-19.

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“…They were initially described, in the 1960s, as plastic-adherent and fibroblast-like cells with clonogenic potential in vitro [10]. Today, they are recognized as a part of stem cell niches in the bone marrow [11] and are known to play a role in immunomodulation [12], as demonstrated by the prominent contribution of the cells in reversing graft-versus-host-disease [13]. Scientific interest in MSCs has developed in recent years, making them one of the most-studied human cell types related to cell-based therapy [14].…”

Section: Introductionmentioning

confidence: 99%

Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study

2020

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Background Clinical application of mesenchymal stromal cells (MSCs) usually requires an in vitro expansion step to reach clinically relevant numbers. In vitro cell expansion necessitates supplementation of basal mammalian cell culture medium with growth factors. To avoid using supplements containing animal substances, human platelet lysates (hPL) produced from expired and pathogen inactivated platelet concentrates can be used in place of fetal bovine serum. However, globally, most transfusion units are currently not pathogen inactivated. As blood banks are the sole source of platelet concentrates for hPL production, it is important to ensure product safety and standardized production methods. In this proof-of-concept study we assessed the feasibility of producing hPL from expired platelet concentrates with pathogen inactivation applied after platelet lysis by evaluating the retention of growth factors, cytokines, and the ability to support MSC proliferation and tri-lineage differentiation. Methodology/Principal findings Bone marrow-derived MSCs (BM-MSCs) were expanded and differentiated using hPL derived from pathogen inactivated platelet lysates (hPL-PIPL), with pathogen inactivation by amotosalen/ultraviolet A treatment applied after lysis of expired platelets. Results were compared to those using hPL produced from conventional expired pathogen inactivated platelet concentrates (hPL-PIPC), with pathogen inactivation applied after blood donation. hPL-PIPL treatment had lower concentrations of soluble growth factors and cytokines than hPL-PIPC treatment. When used as supplementation in cell culture, BM-MSCs proliferated at a reduced rate, but more consistently, in hPL-PIPL than in hPL-PIPC. The ability to support tri-lineage differentiation was comparable between lysates. Conclusion/Significance These results suggest that functional hPL can be produced from expired and untreated platelet lysates by applying pathogen inactivation after platelet lysis. When carried out post-PLOS ONE

show abstract

Efficacy and safety of mesenchymal stromal cells for the prophylaxis of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a meta-analysis of randomized controlled trials

Cited by 34 publications

References 59 publications

Mesenchymal Stromal Cells for Graft Versus Host Disease: Mechanism-Based Biomarkers

Mesenchymal Stromal Cells for Graft Versus Host Disease: Mechanism-Based Biomarkers

Rationale for the clinical use of adipose-derived mesenchymal stem cells for COVID-19 patients

Effects of amotosalen treatment on human platelet lysate bioactivity: A proof-of-concept study

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