Long-Term Complications, Immunologic Effects, and Role of Passage for Outcome in Mesenchymal Stromal Cell Therapy

Bahr, Lena von; Sundberg, Berit; Lönnies, Lena; Sander, Birgitta; Karbach, Holger; Hägglund, Hans; Ljungman, Per; Gustafsson, Britt; Karlsson, Helén; Blanc, Katarina Le; Ringdén, Olle

doi:10.1016/j.bbmt.2011.07.023

Cited by 280 publications

(221 citation statements)

References 22 publications

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“…However, an improved survival was only noted in patients with complete response, 82 for whom 2-year survival was 53% and long-term survival even worse. 48 The results are more promising when used at an early stage of GVHD. 86 Bernardo et al 96 treated grade-II acute GVHD with MSCs and reported no deaths that were attributable to acute GVHD as compared with 26% in retrospective control patients.…”

Section: Discussionmentioning

confidence: 75%

“…At our centre, 31 patients treated with MSCs for acute GVHD or hemorrhagic cystitis were followed for 44 years. 48 The patients who received MSCs from passage 1-2 had better survival (75% at 1 year) than those who received MSCs from passage 3-4 (21%) (Po0.01). Long-term survival was not better than in patients with severe acute GVHD who were not treated with MSCs.…”

Section: Clinical Use Of Bm-derived Mscsmentioning

confidence: 99%

“…7 Despite the fact that MSCs reduce alloreactivity in vitro, it has been difficult to correlate clinical outcome to successful inhibition of mixed lymphocyte reactions with BMMSCs and patient PBMCs as responder cells. 48 MSCs use a variety of different factors in order to suppress immune responses, many of which are secreted. Some of these factors are constitutively produced by MSCs, such as HLA-G5, 49 prostaglandin E 2 (PGE 2 ), 50 and galectins.…”

Section: Immune Modulation By Mscsmentioning

confidence: 99%

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Stromal cells–are they really useful for GVHD?

Kaipe

Erkers

Sadeghi

et al. 2014

Bone Marrow Transplant

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Mesenchymal stromal cells (MSCs) have immunomodulatory effects and are increasingly being used for the treatment of acute and chronic GVHD. Although they seem immuno-privileged, they induce alloresponses, but the risk of immunization is poorly characterized. After infusion, they first reach the lungs, liver and spleen, and are then difficult to trace. Several mechanisms are involved in stromal cells suppressing alloreactivity, such as induction of regulatory T cells, but whether or not this will also affect leukemic relapse or increase infections is not known. Although several encouraging pilot studies have been published, there have been few prospective randomized trials. There may be a bias in the literature, as negative results are seldom published, and there have been few comparative studies with other immunosuppressive regimens. Most animal models have failed to show any effect on GVHD. Several questions remain to be answered for optimization of stromal cell therapy. Which source is optimal-BM, fat, cord or decidua? Can stromal cells be replaced by exosomes, which culture conditions are most appropriate and at what passage and how frequently should cells be administered? More research is required to move stromal cell therapy forward to become an established treatment for acute and chronic GVHD.

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Section: Discussionmentioning

confidence: 75%

Section: Clinical Use Of Bm-derived Mscsmentioning

confidence: 99%

Section: Immune Modulation By Mscsmentioning

confidence: 99%

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Stromal cells–are they really useful for GVHD?

Kaipe

Erkers

Sadeghi

et al. 2014

Bone Marrow Transplant

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“…MSCs show distinct efficacy in graft-versus-host disease (GvHD) patients (18,19) with no, or only minor, side effects. Importantly, no increased risk of tumor development in patients is known, and no ectopic tissue formation has been observed (20,21).…”

mentioning

confidence: 99%

Preserved β-Cell Function in Type 1 Diabetes by Mesenchymal Stromal Cells

et al. 2014

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The retention of endogenous insulin secretion in type 1 diabetes is an attractive clinical goal, which opens possibilities for long-term restoration of glucose metabolism. Mesenchymal stromal cells (MSCs) constitute, based on animal studies, a promising interventional strategy for the disease. This prospective clinical study describes the translation of this cellular intervention strategy to patients with recent-onset type 1 diabetes. Twenty adult patients with newly diagnosed type 1 diabetes were enrolled and randomized to MSC treatment or to the control group. Residual b-cell function was analyzed as C-peptide concentrations in blood in response to a mixed-meal tolerance test (MMTT) at 1-year follow-up. In contrast to the patients in the control arm, who showed loss in both C-peptide peak values and C-peptide when calculated as area under the curve during the 1st year, these responses were preserved or even increased in the MSC-treated patients. Importantly, no side effects of MSC treatment were observed. We conclude that autologous MSC treatment in new-onset type 1 diabetes constitutes a safe and promising strategy to intervene in disease progression and preserve b-cell function.

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“…As described above, the requirement of repeated administration in industrial MSC therapy probably could arise from their dysfunction induced by bulk production. Von Bahr et al reported that the patients who received MSCs from passage 1-2 have better survival (75% at 1 year) than those who receive MSCs from passage 3-4 (21%) (p < 0.01) [47]. In addition, the immune plasticity of MSCs may vary depending on donors.…”

Section: Problems and Future Directions Of Msc Therapy For Acute Gvhdmentioning

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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Long-Term Complications, Immunologic Effects, and Role of Passage for Outcome in Mesenchymal Stromal Cell Therapy

Cited by 280 publications

References 22 publications

Stromal cells–are they really useful for GVHD?

Stromal cells–are they really useful for GVHD?

Preserved β-Cell Function in Type 1 Diabetes by Mesenchymal Stromal Cells

Human Mesenchymal Stem Cell Therapy for Acute Graft Versus Host Disease

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