Sequential Third-Party Mesenchymal Stromal Cell Therapy for Refractory Acute Graft-versus-Host Disease

Sánchez‐Guijo, Fermín; Caballero‐Velázquez, Teresa; López-Villar, Olga; Redondo, Alba; Parody, Rocío; Martı́nez, Carmen; Olavarría, Eduardo; Andreu, Enrique J.; Prósper, Felipe; Díez-Campelo, María; Regidor, C; Villarón, Eva; López-Corral, Lucía; Caballero, Dolores; Cañizo, María-Consuelo del; Pérez-Simón, Josè Antonio

doi:10.1016/j.bbmt.2014.06.015

Cited by 105 publications

(82 citation statements)

References 35 publications

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“…Patients in this study received a median cumulative dose of 6.81×10 6 MSCs per kg bodyweight in a median of three infusions. Overall, the authors report 13% complete remissions and 61% partial responses with no severe or late side effects which could be attributed to the administration of MSCs Sánchez-Guijo and colleagues reported on the safety and efficacy of the administration of four sequential doses of cryopreserved bone marrow-derived MSCs from third-party donors as a second-line treatment for steroid-refractory acute GvHD (42). The MSC administration was well tolerated with the exception of a cardiac ischemic event that occurred twice in a patient with a prior history of cardiac ischemia.…”

Section: Box 2 Effects Of Mscs On Acute Gvhd Symptoms In Different Stmentioning

confidence: 99%

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles

Giebel

Kordelas²,

Börger

2017

Stem Cell Investig.

126

115

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Within the last two decades mesenchymal stem/stromal cells (MSCs) emerged after hematopoietic stem cells as the second most investigated and applied somatic stem cell entity so far. MSCs mediate immunosuppressive as well as pro-regenerative activities. Against the initial assumption, MSCs may not primarily exert their therapeutic functions in a cellular but rather in a paracrine manner. Here, extracellular vesicles (EVs), such as exosomes and microvesicles, have been identified as major mediators of these paracrine effects. Meanwhile, MSC-EVs have been applied to an increasing amount of different animal models and were tested in a patient suffering from steroid-refractory acute graft-versus-host disease (acute GvHD) as well as in a patient cohort with chronic kidney disease. So far, the MSC-EV administration appears to be safe in humans and all tested animal models. Improvements were reported in all settings. Thus, MSC-EVs appear as promising novel therapeutic agents which might help to improve disease associated symptoms in millions of patients. Here, we review some of the milestones in the field, briefly discuss challenges and highlight clinical aspects of acute GvHD and its treatment with MSCs and MSC-EVs.

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Section: Box 2 Effects Of Mscs On Acute Gvhd Symptoms In Different Stmentioning

confidence: 99%

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles

Giebel

Kordelas²,

Börger

2017

Stem Cell Investig.

126

115

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“…Two-year overall survival in the patients with CR (52%, 95%CI; 34-70%) was better than that in the patients with PR or no response (16%, 95%CI; 0-32%, p = 0.018). Subsequently, many studies of MSC therapy for refractory acute GVHD have been conducted until now (summarized in Table 1) [29][30][31][32][33][34][35][36][37]. MSCs were mostly derived from third party donors in all the studies.…”

Section: Clinical Studies Of Msc Therapy For Refractory Acute Gvhd Usmentioning

confidence: 99%

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

Yoshioka¹,

Miura²

2016

Transl Med

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Acute graft versus host disease (GVHD) is the most critical complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The understanding of major histocompatibility complex (MHC) and the development of acute GVHD prophylaxis have contributed to decreasing the incidence of severe acute GVHD. However, these progresses expand the chance of receiving allo-HSCT from human leukocyte antigen (HLA) mismatched donor. In addition, the expanding of indication for allo-HSCT to elderly patients or patients with organ dysfunction by the pervasiveness of reduced-intensity conditioning is associated with increased risk of acute GVHD. Unexpectedly, severe refractory acute GVHD can occur even in allo-HSCT from HLA matched sibling donor. The first line therapy for severe acute GVHD is corticosteroid, but the second line therapy has not been established and the prognosis of steroid-resistant acute GVHD remains poor. Recently, the efficacy of human bone marrow mesenchymal stem cell (MSC) therapy for steroid-resistant acute GVHD has been consistently reported. MSCs are approved as a cell therapy drug for steroid-resistant acute GVHD in some countries. We here review the history and the future of MSC therapy for acute GVHD.

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“…Other than tolerance induction, cellular therapy of GvHD is another aspect under clinical investigation [64,65]. In cases of steroid-refractory GvHD in HSCtransplanted patients, repetitive third-party BM-MSC infusions over 3 weeks achieved more than 70% responders with cessation of GvHD symptoms [66], which is in line with a very recent report [64]. Fortunately, human freeze-thawed BM-MSCs have recently been found to retain their immunosuppressive activity against GvHD, potentially allowing for third party off-the-shelf cell products for therapy of such conditions [67].…”

Section: Routes Of Administrationmentioning

confidence: 99%

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

Schweizer

Gorantla

Plock

2015

Current Opinion in Organ Transplantation

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PURPOSE OF REVIEW Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. RECENT FINDINGS Experimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSC-induced long-term operational tolerance in experimental VCA is mediated by induction of mixed donor-specific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. SUMMARY Cellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA. Purpose of review Over the past decade, clinical vascularized composite allotransplantation (VCA) has enabled functional and quality of life restoration in a wide range of indications secondary to devastating tissue loss. However, the spectre of toxicity and long-term complications of chronic immunosuppression has curtailed the momentum of VCA. This study summarizes the literature evidence behind successful mesenchymal stem cell (MSC)-based cell therapies highlighting their multipronged immunomodulatory, restorative and regenerative characteristics with special emphasis towards VCA applications. Recent findingsExperimental and clinical studies in solid organs and VCA have confirmed that MSCs facilitate immunosuppression-free allograft survival or tolerance, stimulate peripheral nerve regeneration, attenuate ischaemia-reperfusion injury, and improve tissue healing after surgery. It has been hypothesized that MSCinduced long-term operational tolerance in experimental VCA is mediated by induction of mixed donorspecific chimerism and regulatory T-cell mechanisms. All these characteristics of MSCs could thus help expand the scope and clinical feasibility of VCA. SummaryCellular therapies, especially those focusing on MSCs, are emerging in solid organ transplantation including VCA. Although some clinical trials have begun to assess the effects of MSCs in solid organ transplantation, much scientific domain remains uncharted, especially for VCA.

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Sequential Third-Party Mesenchymal Stromal Cell Therapy for Refractory Acute Graft-versus-Host Disease

Cited by 105 publications

References 35 publications

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles

Clinical potential of mesenchymal stem/stromal cell-derived extracellular vesicles

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

Premise and promise of mesenchymal stem cell-based therapies in clinical vascularized composite allotransplantation

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