Mesenchymal stromal cells for prevention and treatment of graft-versus-host disease

Introna, Martino; Rambaldi, Alessandro

doi:10.1097/mot.0000000000000158

Cited by 53 publications

(44 citation statements)

References 60 publications

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“…Since 2004, the use of cryopreserved allogeneic MSC for the treatment of steroid-refractory acute graft-versus-host disease (aGvHD) has become medical practice in many countries [11, 12]. …”

Section: Introductionmentioning

confidence: 99%

Generation of mesenchymal stromal cells from cord blood: evaluation of in vitro quality parameters prior to clinical use

et al. 2017

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BackgroundIncreasing evidence suggests the safety and efficacy of mesenchymal stromal cells (MSC) as advanced therapy medicinal products because of their immunomodulatory properties and supportive role in hematopoiesis. Although bone marrow remains the most common source for obtaining off-the-shelf MSC, cord blood (CB) represents an alternative source, which can be collected noninvasively and without major ethical concerns. However, the low estimated frequency and inconsistency of successful isolation represent open challenges for the use of CB-derived MSC in clinical trials. This study explores whether CB may represent a suitable source of MSC for clinical use and analyzes several in vitro parameters useful to better define the quality of CB-derived MSC prior to clinical application.MethodsCB units (n = 50) selected according to quality criteria (CB volume ≥ 20 ml, time from collection ≤ 24 h) were cultured using a standardized procedure for CB-MSC generation. MSC were analyzed for their growth potential and secondary colony-forming capacity. Immunophenotype and multilineage differentiation potential of culture-expanded CB-MSC were assessed to verify MSC identity. The immunomodulatory activity at resting conditions and after inflammatory priming (IFN-γ-1b and TNF-α for 48 hours) was explored to assess the in vitro potency of CB-MSC prior to clinical application. Molecular karyotyping was used to assess the genetic stability after prolonged MSC expansion.ResultsWe were able to isolate MSC colonies from 44% of the processed units. Our results do not support a role of CB volume in determining the outcome of the cultures, in terms of both isolation and proliferative capacity of CB-MSC. Particularly, we have confirmed the existence of two different CB-MSC populations named short- and long-living (SL- and LL-) CBMSC, clearly diverging in their growth capacity and secondary colony-forming efficiency. Only LL-CBMSC were able to expand consistently and to survive for longer periods in vitro, while preserving genetic stability. Therefore, they may represent interesting candidates for therapeutic applications. We have also observed that LL-CBMSC were not equally immunosuppressive, particularly after inflammatory priming and despite upregulating priming-inducible markers.ConclusionsThis work supports the use of CB as a potential MSC source for clinical applications, remaining more readily available compared to conventional sources. We have provided evidence that not all LL-CBMSC are equally immunosuppressive in an inflammatory environment, suggesting the need to include the assessment of potency among the release criteria for each CB-MSC batch intended for clinical use, at least for the treatment of immune disorders as GvHD.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-016-0465-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Generation of mesenchymal stromal cells from cord blood: evaluation of in vitro quality parameters prior to clinical use

et al. 2017

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“…The therapeutic effects of MSCs have been demonstrated in experimental animal models of a wide variety of inflammatory diseases (10–17). The positive outcome of these preclinical studies supported the use of MSCs in clinical trials in different inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Crohn’s disease (16, 18–21).…”

Section: Introductionmentioning

confidence: 99%

Intralymphatic Administration of Adipose Mesenchymal Stem Cells Reduces the Severity of Collagen-Induced Experimental Arthritis

et al. 2017

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Mesenchymal stem cells (MSCs) are multipotent stromal cells with immunomodulatory properties. They have emerged as a very promising treatment for autoimmunity and inflammatory diseases such as rheumatoid arthritis. Previous studies have demonstrated that MSCs, administered systemically, migrate to lymphoid tissues associated with the inflammatory site where functional MSC-induced immune cells with a regulatory phenotype were increased mediating the immunomodulatory effects of MSCs. These results suggest that homing of MSCs to the lymphatic system plays an important role in the mechanism of action of MSCs in vivo. Thus, we hypothesized that direct intralymphatic (IL) (also referred as intranodal) administration of MSCs could be an alternative and effective route of administration for MSC-based therapy. Here, we report the feasibility and efficacy of the IL administration of human expanded adipose mesenchymal stem cells (eASCs) in a mouse model of collagen-induced arthritis (CIA). IL administration of eASCs attenuated the severity and progression of arthritis, reduced bone destruction and increased the levels of regulatory T cells (CD25+Foxp3+CD4+ cells) and Tr1 cells (IL10+CD4+), in spleen and draining lymph nodes. Taken together, these results indicate that IL administration of eASCs is very effective in modulating established CIA and may represent an alternative treatment modality for cell therapy with eASCs.

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“…Another approach would be to combine hiPSC transplantation with adoptive T-regulatory (T reg ) cell or mesenchymal stromal cell (MSC) transfer. These cells have anti-inflammatory modulators and have demonstrated efficacy for preventing immune responses in human clinical trials [82–84]. …”

Section: Remaining Barriers For Clinical Implementation Of Human Plurmentioning

confidence: 99%

Pluripotent stem cell applications for regenerative medicine

Angelos

Kaufman

2015

Current Opinion in Organ Transplantation

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Mesenchymal stromal cells for prevention and treatment of graft-versus-host disease

Cited by 53 publications

References 60 publications

Generation of mesenchymal stromal cells from cord blood: evaluation of in vitro quality parameters prior to clinical use

Generation of mesenchymal stromal cells from cord blood: evaluation of in vitro quality parameters prior to clinical use

Intralymphatic Administration of Adipose Mesenchymal Stem Cells Reduces the Severity of Collagen-Induced Experimental Arthritis

Pluripotent stem cell applications for regenerative medicine

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