Multipotent Mesenchymal Stromal Cells for the Prophylaxis of Acute Graft-versus-Host Disease—A Phase II Study

Кузьмина, Л А; Petinati, Nataliya; Паровичникова, Е Н; Lubimova, L. S.; Грибанова, Е О; Gaponova, Tatjana V.; Shipounova, Irina N.; Zhironkina, Oxana A.; Bigildeev, Alexey; Svinareva, D. A.; Ni, Drize; Vg, Savchenko

doi:10.1155/2012/968213

Cited by 102 publications

(70 citation statements)

References 53 publications

(54 reference statements)

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“…98 Acute GVHD and survival were not statistically significantly different between the groups. 98 Kuzmina et al 99 performed a randomized prophylactic study with an MSC dose of 1 Â 10 6 /kg at the time of blood count recovery. Acute GVHD of grades II-IV developed in only 5% of the MSC patients as compared with 39% of the controls (P ¼ 0.002).…”

Section: Stromal Cells For Prevention Of Gvhdmentioning

confidence: 99%

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: Stromal Cells For Prevention Of Gvhdmentioning

confidence: 99%

Stromal cells–are they really useful for GVHD?

Kaipe

Erkers

Sadeghi

et al. 2014

Bone Marrow Transplant

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“…However, few studies have been performed with enriched populations of CD3 + T cells [10,13,14]. This is important because CD4 + and CD8 + T cells are the major effector cells in immunological diseases such as graft-versus-host disease (GVHD) [15], and thus it is important to determine the immunosuppression properties of MSCs on these populations and determine their potential for cell therapies.…”

Section: Introductionmentioning

confidence: 99%

“…Bone marrow (BM) is the main source of MSCs [15]; BM-MSCs have been used in cell therapy protocols to reduce GVHD [15,16]. However, BM presents some disadvantages, such as the difficulty in finding donors, the cost and invasiveness of the collection procedure, and agerelated decreases in MSCs numbers [17].…”

Section: Introductionmentioning

confidence: 99%

Human Mesenchymal Stromal Cells from Adult and Neonatal Sources: A Comparative In Vitro Analysis of Their Immunosuppressive Properties Against T Cells

Castro-ManrrezaMarta

MayaniHéctor

García

et al. 2014

Stem Cells and Development

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Bone marrow-mesenchymal stromal cells (BM-MSCs) have immunosuppressive properties and have been used in cell therapies as immune regulators for the treatment of graft-versus-host disease. We have previously characterized several biological properties of MSCs from placenta (PL) and umbilical cord blood (UCB), and compared them to those of BM-the gold standard. In the present study, we have compared MSCs from BM, UCB, and PL in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3 + T cells. Our results confirm the immunosuppressive potential of BM-MSCs, and demonstrate that MSCs from UCB and, to a lesser extent PL, also have immunosuppressive potential. In contrast to PL-MSCs, BMMSCs and UCB-MSCs significantly inhibited the proliferation of both CD4+ and CD8 + activated T cells in a cell-cell contact-dependent manner. Such a reduced proliferation in cell cocultures correlated with upregulation of programmed death ligand 1 on MSCs and cytotoxic T lymphocyte-associated Ag-4 (CTLA-4) on T cells, and increased production of interferon-g, interleukin-10, and prostaglandin E2. Importantly, and in contrast to PL-MSCs, both BM-MSCs and UCB-MSCs favored the generation of T-cell subsets displaying a regulatory phenotype CD4 + CD25 + CTLA-4 + . Our results indicate that, besides BM-MSCs, UCB-MSCs might be a potent and reliable candidate for future therapeutic applications.

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“…Activated and non-activated allogeneic lymphocytes were explanted onto MSC cultures at a ratio of approximately 10:1 with RPMI-1640 medium with 10% FBS. This ratio of lymphocytes to MSCs adequately reflects the situation after intravenous administration of MSCs to prevent or treat a GVHD after the transplantation of allogeneic hematopoietic stem cells [27,47]. Some samples of MSCs were pretreated with IFN-γ for 4 hours.…”

Section: Resultsmentioning

confidence: 99%