Mesenchymal stromal cell therapy for steroid-refractory acute and chronic graft versus host disease: a phase 1 study

Herrmann, Richard; Sturm, M.; Shaw, Kathryn; Purtill, Duncan; Cooney, Julian; Wright, Matthew; Phillips, Michael; Cannell, Paul

doi:10.1007/s12185-011-0989-2

Cited by 89 publications

(69 citation statements)

References 21 publications

(28 reference statements)

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“…No side effects were reported [7] . Other centres, including ours, have reported similar outcomes [9,10] .…”

Section: Background To Mesenchymal Stromal Cell Therapysupporting

confidence: 76%

“…Cells are expanded in culture, but not by more than 5 populations, or passages. Cells are cryopreserved, and then prior to release for intravenous administration, are evaluated for cell viability, negative microbiological contamination, cytogenetic abnormalities, and the core MSC characteristics according to the International Society for Cellular Therapy [9,11] . This occurs in a dedicated laboratory, licensed by the Australian regulator, the Therapeutic Goods Administration.…”

Section: Principles Of Preparation and Administrationmentioning

confidence: 99%

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Mesenchymal Stromal Cell Therapy in Crohn's Disease

Forbes

2017

Dig Dis

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Background: Mesenchymal stromal cells (MSC) are multipotent adult stem cells with immunomodulatory properties. They uniquely express HLA class I antigen at a low level, and do not express HLA class II. Hence, for allogeneic administration, donor to recipient matching is not required; yet a prolonged chimeric state does not occur. Contrary to haematopoietic stem cell transplantation, cytotoxic drug therapy is not required to harvest, or administer, cells. Key Messages: MSC are obtained from marrow, adipose tissue or placenta. In our centre, MSC are isolated from a 10 ml donor marrow aspirate, by virtue of their adherence to plastic. They are expanded in culture, cryopreserved, and subjected to strict quality controls before release for intravenous administration. These activities occur in a dedicated, nationally accredited, laboratory. Initial observations of allogeneic MSC efficacy were in graft-versus-host disease. Both autologous and allogeneic MSC have since been evaluated in biologic refractory luminal and fistulising Crohn's disease (CD). Data from early-phase studies have suggested efficacy for luminal disease when allogeneic MSC were given intravenously and also suggested efficacy for fistulising disease when either allogeneic or autologous MSC were administered into fistulas. MSC treatment is not reported to have caused serious adverse events. Although in vitro criteria for defining MSC exist, a major challenge lies in how to define MSC for clinical use. MSC function in vivo is likely to be dependent upon donor immunological characteristics, and widely varying manufacturing processes between laboratories. MSC dose, frequency of administration, stage of disease, and presence of concomitant immunosuppression also require to be defined. Conclusions: MSC therapy may have future utility in CD, but considerable work is first required to determine appropriate phenotypic and functional characteristics of administered cells.

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“…No side effects were reported [7] . Other centres, including ours, have reported similar outcomes [9,10] .…”

Section: Background To Mesenchymal Stromal Cell Therapysupporting

confidence: 76%

Section: Principles Of Preparation and Administrationmentioning

confidence: 99%

Mesenchymal Stromal Cell Therapy in Crohn's Disease

Forbes

2017

Dig Dis

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“…8 The treatment protocol was basically the same as described above, and the observation time was pro- Many prospective studies using MSCs for SR-aGVHD have been conducted Table 1 . 7,8,18,[20][21][22][24][25][26][27][28][29][30][31][32][33][34] As shown, the patients who were enrolled and the defined endpoints varied.…”

Section: Clinical Trials Conducted In Japanmentioning

confidence: 99%

Mesenchymal Stem Cells: The First Approved Stem Cell Drug in Japan

Najima

Ohashi

2017

Journal of Hematopoietic Cell Transplantation

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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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Mesenchymal stromal cell therapy for steroid-refractory acute and chronic graft versus host disease: a phase 1 study

Cited by 89 publications

References 21 publications

Mesenchymal Stromal Cell Therapy in Crohn's Disease

Mesenchymal Stromal Cell Therapy in Crohn's Disease

Mesenchymal Stem Cells: The First Approved Stem Cell Drug in Japan

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

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