Mesenchymal stem cells provide prophylaxis against acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: A meta-analysis of animal models

Wang, Li; Zhang, Haiyan; Guan, Li; Zhao, Shasha; Gu, Zhenyang; Wei, Huaping; Gao, Zhe; Wang, Feiyan; Yang, Nan; Luo, Lan; Li, Yonghui; Wang, Lili; Liu, Dai‐Hong; Gao, Chunji

doi:10.18632/oncotarget.11238

Cited by 13 publications

(7 citation statements)

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“…MSCs exert their functions, such as proliferation, secreted factors, antitumor effects, and cytotoxicity, in a dose-dependent manner [ 60 ], suggesting that MSCs produce a better effect when administered at relatively high doses [ 19 , 60 ]. According to previous studies, high doses of MSCs are inhibitory in mixed lymphocyte cultures, while low doses promote lymphocyte proliferation [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

“…According to previous studies, high doses of MSCs are inhibitory in mixed lymphocyte cultures, while low doses promote lymphocyte proliferation [ 48 ]. However, this dose-response effect may not be beneficial when the MSC dose is above a certain threshold [ 60 , 61 ]. Numerous routes of MSC delivery to the human body have been used, including intramuscular or direct injection into tissues or organs [ 62 , 63 ], intravenous (IV) infusion [ 63 – 65 ], intraarterial (IA) infusion [ 63 , 66 ], and intra-bone marrow injection [ 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of mesenchymal stem cells co-infusion in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

Luo

Zhang

et al. 2021

Stem Cell Res Ther

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Background Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is life-saving for severe hematological conditions. However, its outcomes need further improvement, and co-infusion of mesenchymal stem cells (MSCs) may show promise. A growing body of research on this subject exists, while the results of different trials are conflicting. A systematic review and meta-analysis is needed to appraise the real efficacy and safety of MSC co-transplantation in allo-HSCT. Methods Studies comparing MSC co-transplantation in allo-HSCT with allo-HSCT alone were searched in six medical databases from inception to June 10, 2020. The primary outcomes were engraftment and graft-versus-host disease (aGVHD and cGVHD, respectively). Other outcomes included overall survival (OS), relapse rate (RR), non-relapse mortality (NRM), and immune reconstitution. Information was independently extracted by two investigators. Methodological quality was assessed using the Cochrane Collaboration tool. Meta-analysis was performed using RevMan 5.4. Results Six randomized controlled trials (RCTs) and 13 non-randomized controlled trials (nRCTs) were included. MSC co-infusion resulted in shorter times to neutrophil engraftment (RCTs: standardized mean difference (SMD) − 1.20, p = 0.04; nRCTs: SMD − 0.54, p = 0.04) and platelet engraftment (RCTs: SMD − 0.60, p = 0.04; nRCTs: SMD − 0.70, p = 0.01), a lower risk of cGVHD (RCTs: risk ratio (RR) 0.53, p = 0.01; nRCTs: RR 0.50, p < 0.01), and a slightly positive trend towards reducing the risk of aGVHD and NRM, without affecting RR and OS. Subgroup analyses revealed that when MSCs were co-transplanted, children and adolescents, and patients receiving human leukocyte antigen (HLA)-nonidentical HSCT showed improvements in engraftment and incidence of GVHD and NRM; adults and patients who received HLA-identical HSCT had lower cGVHD; patients with malignancies exhibited improvements in GVHD and NRM incidence; and patients with non-malignancies experienced accelerated engraftment. Notably, a reduced OS was observed in patients with hematological malignancies undergoing HLA-identical HSCT. Conclusion MSC co-infusion generally improved engraftment and reduced cGVHD, without increasing mortality or relapse. Regarding aGVHD and NRM, the effects of MSCs were not quite significant. Specifically, our data support the utilization of MSC co-transplantation in children and young individuals with HLA-nonidentical HSCT, but not in adult patients with hematological malignancies undergoing HLA-identical HSCT.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of mesenchymal stem cells co-infusion in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

Luo

Zhang

et al. 2021

Stem Cell Res Ther

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“…In addition, MSCs have been indicated to have stronger immunomodulatory properties compared to other stem cell sources, and have been shown to suppress T cell, B cell, dendritic cell and natural killer cell activity [ 75 , 79 , 80 , 81 , 82 ]. MSCs are therefore not only attractive for tissue regeneration via their multilineage differentiation potential, but also for treatment of autoimmune diseases such rheumatoid arthritis (RA), and to help bypass graft-versus-host disease (GVHD) [ 83 , 84 , 85 , 86 ]. In addition, MSCs have the obvious benefit over ESCs and iPSCs for cartilage TE, that they are already committed to mesoderm lineages [ 87 ], and therefore require less in vitro programming.…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

The Good the Bad and the Ugly of Glycosaminoglycans in Tissue Engineering Applications

2017

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High sulfation, low cost, and the status of heparin as an already FDA- and EMA- approved product, mean that its inclusion in tissue engineering (TE) strategies is becoming increasingly popular. However, the use of heparin may represent a naïve approach. This is because tissue formation is a highly orchestrated process, involving the temporal expression of numerous growth factors and complex signaling networks. While heparin may enhance the retention and activity of certain growth factors under particular conditions, its binding ‘promiscuity’ means that it may also inhibit other factors that, for example, play an important role in tissue maintenance and repair. Within this review we focus on articular cartilage, highlighting the complexities and highly regulated processes that are involved in its formation, and the challenges that exist in trying to effectively engineer this tissue. Here we discuss the opportunities that glycosaminoglycans (GAGs) may provide in advancing this important area of regenerative medicine, placing emphasis on the need to move away from the common use of heparin, and instead focus research towards the utility of specific GAG preparations that are able to modulate the activity of growth factors in a more controlled and defined manner, with less off-target effects.

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“… 119 There are some prophylactic procedures that used for reducing the severity and incidence of GVHD after allogeneic HSCT such as ex vivo depletion of donor T cells by active depletion or enrichment of CD34 + HSCs and immunosuppressive agents. 120 , 121 Nevertheless, ex vivo depletion of donor T cells causes an increased rate of graft versus leukemia (GVL) effect, infection because of the removing of donor T cells, and relapse. Moreover, immunosuppressive agents that are first-line factors for treatment of GVHD associated with low response rate, decreased immune system reconstitution in patients, and the increased risk of GVL effect and opportunistic infections.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, immunosuppressive agents that are first-line factors for treatment of GVHD associated with low response rate, decreased immune system reconstitution in patients, and the increased risk of GVL effect and opportunistic infections. 120 , 121 For these reasons, new strategies are needed to prevent and treat the GVHD.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Mesenchymal Stem Cell-Derived Extracellular Vesicles on Hematopoietic Stem Cells Fate

Timari¹,

Shamsasenjan²,

Movassaghpour³

et al. 2017

Adv Pharm Bull

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Hematopoietic stem cells (HSCs) are multipotent stem cells, with self-renewal ability as well as ability to generate all blood cells. Mesenchymal stem cells (MSCs) are multipotent stem cells, with self-renewal ability, and capable of differentiating into a variety of cell types. MSCs have supporting effects on hematopoiesis; through direct intercellular communications as well as secreting cytokines, chemokines, and extracellular vesicles (EVs). Recent investigations demonstrated that some biological functions and effects of MSCs are mediated by their EVs. MSC-EVs are the cell membrane and endosomal membrane compartments, which are important mediators in the intercellular communications. MSC-EVs contain some of the molecules such as proteins, mRNA, siRNA, and miRNA from their parental cells. MSC-EVs are able to inhibit tumor, repair damaged tissue, and modulate immune system responses. MSC-EVs compared to their parental cells, may have the specific safety advantages such as the lower potential to trigger immune system responses and limited side effects. Recently some studies demonstrated the effect of MSC-EVs on the expansion, differentiation, and clinical applications of HSCs such as improvement of hematopoietic stem cell transplantation (HSCT) and inhibition of graft versus host disease (GVHD). HSCT may be the only therapeutic choice for patients who suffer from malignant and non-malignant hematological disorders. However, there are several severe side eﬀects such GVHD that restricts the successfulness of HSCT. In this review, we will discuss the most important effects of MSCs and MSC-EVs on the improvement of HSCT, inhibition and treatment of GVHD, as well as, on the expansion of HSCs.

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Mesenchymal stem cells provide prophylaxis against acute graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: A meta-analysis of animal models

Cited by 13 publications

References 73 publications

Efficacy and safety of mesenchymal stem cells co-infusion in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

Efficacy and safety of mesenchymal stem cells co-infusion in allogeneic hematopoietic stem cell transplantation: a systematic review and meta-analysis

The Good the Bad and the Ugly of Glycosaminoglycans in Tissue Engineering Applications

The Effect of Mesenchymal Stem Cell-Derived Extracellular Vesicles on Hematopoietic Stem Cells Fate

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