Long-Term Follow-Up After the Application of Mesenchymal Stromal Cells in Children and Adolescents with Steroid-Refractory Graft-Versus-Host Disease

Döring, Michaela; Stanchi, Karin Melanie Cabanillas; Lenglinger, Katrin; Treuner, Claudia; Gieseke, Friederike; Erbacher, Annika; Mezger, Markus; Vaegler, Martin; Schlegel, Paul‐Gerhardt; Greil, Johann; Riehm, C. Bettoni da Cunha; Faul, Christoph; Schumm, Michael; Lang, Peter; Handgretinger, Rupert; Müller, Ingo

doi:10.1089/scd.2020.0191

Cited by 6 publications

(3 citation statements)

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“…Recent clinical studies have shown that MSCs can mediate not only short-term, but also long-term responses in patients with steroid-refractory GvHD ( 36 ). Although we ca hypothesize that single or multiple infusions of CXCR4-IL10-MSCs might also exert improved long-term responses in patients with either acute or chronic GvHD, further experimental studies will be required to confirm this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Improved efficacy of mesenchymal stromal cells stably expressing CXCR4 and IL-10 in a xenogeneic graft versus host disease mouse model

et al. 2023

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Previous clinical trials have shown that mesenchymal stromal cells (MSCs) can modulate graft versus host disease (GvHD) after allogeneic hematopoietic transplantation, although with variable efficacy. To improve the anti-GvHD effect of these cells, adipose tissue derived-human MSCs (Ad-MSCs) were transduced with a lentiviral vector conferring stable expression of CXCR4, a molecule involved in cell migration to inflamed sites, and IL-10, a cytokine with potent anti-inflammatory properties. In vitro experiments showed that the expression of these molecules in Ad-MSCs (named CXCR4-IL10-MSCs) efficiently enhanced their migration towards SDF-1α and also improved their immunomodulatory properties compared to unmodified Ad-MSCs (WT-MSCs). Moreover, using a humanized GvHD mouse model, CXCR4-IL10-MSCs showed improved therapeutic effects, which were confirmed by histopathologic analysis in the target organs. Additionally, compared to WT-MSCs, CXCR4-IL10-MSCs induced a more marked reduction in the number of pro-inflammatory Th1 and Th17 cells, a higher polarization towards an anti-inflammatory T cell profile (CD3+-IL10+ cells), and increased the number of regulatory T and B cells. Our in vitro and in vivo studies strongly suggest that CXCR4-IL10-MSCs should constitute an important new generation of MSCs for the treatment of GvHD in patients transplanted with allogeneic hematopoietic grafts.

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Section: Discussionmentioning

confidence: 99%

Improved efficacy of mesenchymal stromal cells stably expressing CXCR4 and IL-10 in a xenogeneic graft versus host disease mouse model

et al. 2023

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“…The therapeutic effects of MSCs are multifaceted and include paracrine activity through the secretion of proteins, GvHD. Long-term adverse effects like secondary malignancy were not detected (53).…”

Section: Msc Treatment In Gvhdmentioning

confidence: 98%

Mesenchymal Stem Cell Applications in Graft Versus Host Disease

GÜRSOY,

GÜRLEK GÖKÇEBAY,

ÖZBEK

2024

Türkiye Çocuk Hast Derg

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Allogeneic hematopoietic stem cell transplantation stands as a promising cure for a variety of diseases. However, the potential of acute or chronic graft-versus-host disease (GvHD), which leads to significant morbidity and mortality, remains a cause for concern. GvHD occurs due to the complex interactions of immune cells from the graft and the host cells. Despite the existence of prophylactic treatments, GvHD may still occur, and the resistance to conventional therapies necessitates novel approaches and treatments. Mesenchymal stem cells, which are pluripotent stem cells capable of self-renewal and multilineage differentiation, have gained attention for their low immunogenicity and ability to be sourced from various origins. They have shown promise as therapeutic tools for the cell-based treatment of inflammatory, immune-mediated, and degenerative diseases owing to their remarkable abilities in immunomodulation, immunosuppression, and tissue regeneration. In GvHD, MSCs have demonstrated therapeutic potential through paracrine activity and organelle transfer via nanotubes, microvesicles, or exosomes. The emergence of MSCs as a treatment for severe steroid-resistant GvHD gained attention in the early 2000s. While initial studies have demonstrated encouraging results in the use of MSCs for the prevention of GvHD, there is still a need for further investigation. Therefore, in this current review, we aim to delve deeper into MSC’s features and their clinical applications in the case of GvHD treatment.

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“…MSCs can be isolated from various tissues, including BM, adipose tissue (AD), and umbilical cord (UC; UC blood and Wharton's jelly) [15] or induced from pluripotent stem cells [16], and rapidly expanded on a clinical scale using a standard monolayer culture method [15]. The risk of tumor formation with MSCs is considered extremely low owing to their genetic stability [17], and several in vivo tumorigenicity tests [18] and long-term follow-up of patients with MSC transplantation [19] revealed no tumor formation. Moreover, low immunogenicity is another unique characteristic of MSCs, and allogeneic MSC transplantation rarely causes rejection because MSCs express low levels of major histocompatibility complex (MHC) class I and exceptionally low levels of MHC class II and costimulatory molecules (CD40, CD80, and CD86) [20,21].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

Takayama

Kusamori

Nishikawa

2021

Expert Opinion on Drug Delivery

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Introduction: Drug delivery to solid tumors remains a significant therapeutic challenge. Mesenchymal stem/stromal cells (MSCs) home to tumor tissues and can be employed as tumor targeted drug/gene delivery vehicles. Reportedly, therapeutic gene-or anti-cancer drug-loaded MSCs have shown remarkable anti-tumor effects in preclinical studies, and some clinical trials for assessing therapeutic MSCs in patients with cancer have been registered. Areas covered: In the present review, we first discuss the source and interdonor heterogeneity of MSCs, their tumor-homing mechanism, and the route of MSC administration in MSC-based cancer therapy. We then summarize the therapeutic applications of MSCs as a drug delivery vehicle for therapeutic genes or anti-cancer drugs and the drug delivery mechanism from drug-loaded MSCs to cancer cells. Expert opinion: Although numerous preclinical studies have revealed significant anti-tumor effects, several clinical trials assessing MSC-based cancer gene therapy have failed to demonstrate corroborative results, documenting limited therapeutic effects. Notably, a successful clinical outcome with MSC-based cancer therapy would require the interdonor heterogeneity of administered MSCs to be resolved, along with improved tumor-homing efficiency and optimized drug delivery efficiency from MSCs to cancer cells.

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Long-Term Follow-Up After the Application of Mesenchymal Stromal Cells in Children and Adolescents with Steroid-Refractory Graft-Versus-Host Disease

Cited by 6 publications

References 50 publications

Improved efficacy of mesenchymal stromal cells stably expressing CXCR4 and IL-10 in a xenogeneic graft versus host disease mouse model

Improved efficacy of mesenchymal stromal cells stably expressing CXCR4 and IL-10 in a xenogeneic graft versus host disease mouse model

Mesenchymal Stem Cell Applications in Graft Versus Host Disease

Mesenchymal stem/stromal cells as next-generation drug delivery vehicles for cancer therapeutics

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