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

Castro-ManrrezaMarta, E; MayaniHéctor,; García, Alberto Monroy; Flores-Figueroa, Eugenia; Chávez-RuedaKarina,; Legorreta-HaquetVictoria,; Santiago‐Osorio, Edelmiro; José, MontesinosJuan

doi:10.1089/scd.2013.0363

Cited by 84 publications

(101 citation statements)

References 62 publications

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“…Indeed, MSCs have been shown to significantly inhibit B‐cell proliferation and maturation as well as NK cells, resulting in less secretion of soluble immune mediators and NK‐mediated cytotoxicity, respectively. Consistent with these results, MSCs have recently been shown to inhibit the proliferation of CD4 + /CD8 + ‐activated T cells by cell–cell contact . MSCs may even suppress T‐cell proliferation indirectly by regulating the proliferation and maturation of immune‐regulatory DC, which trigger generation of regulatory T cells …”

Section: Role Of Mscs In Cancer Pathogenesissupporting

confidence: 53%

Double‐edged sword of mesenchymal stem cells: Cancer‐promoting versus therapeutic potential

2017

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Mesenchymal stem cells (MSCs) derived from adipose tissue, bone marrow, cord blood, and other tissues, have recently attracted much attention as potential therapeutic agents in various diseases because of their trans‐differentiation capacity. However, recent studies have suggested that MSCs also appear to contribute to tumor pathogenesis by supporting tumor microenvironments, increasing tumor growth, and eliciting antitumor immune responses. Although some studies suggest that MSCs have inhibitory effects on tumor development, they are overwhelmed by a number of studies showing that MSCs exert stimulatory effects on tumor pathogenesis. In the present review, we summarize a number of findings to provide current information about the therapeutic potential of MSCs in various diseases. We then discuss the potential roles of MSCs in tumor progression.

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Section: Role Of Mscs In Cancer Pathogenesissupporting

confidence: 53%

Double‐edged sword of mesenchymal stem cells: Cancer‐promoting versus therapeutic potential

2017

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“…Under such circumstances, the induced IL-10 functions at the crossroads of immune stimulation, whereas the outcome of this stimulation is mainly depended on the role of additional immune effectors [141]. The IL-10 shifts (activates or suppresses) innate and adaptive immunity of central and peripheral immune system in an immediate and effective way from the view-point of organism, tumor, or infective agent [57, 81,89,135,160,162,163]. Thus, induction of IL-10 mRNA by DCs has been observed only 3 h after infection with Newcastle disease virus [74].…”

Section: Il-10-an Indicator and Time-dependent Effector Of Immunity Smentioning

confidence: 99%

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

Mingomataj

Bakiri

2015

Clinic Rev Allerg Immunol

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The interleukin-10 (IL-10) is generally considered as the most important cytokine with anti-inflammatory properties and one of the key cytokines preventing inflammation-mediated tissue damage. In this respect, IL-10 producing cells play a crucial role in the outcome of infections, allergy, autoimmune reactions, tumor development, and transplant tolerance. Based on recent findings with regard to the mentioned clinical conditions, this review attempts to shed some light on the IL-10 functions, considering this cytokine as inherent inducer of the switching immunity. While acute infections and vaccinations are associated by IL-10 enhanced during few weeks, chronic parasitoses, tumor diseases, allergen-specific immunotherapy, transplants, and use of immune-suppressor drugs show an increased IL-10 level along months or years. With regard to autoimmune pathologies, the IL-10 increase is prevalently observed during early stages, whereas the successive stages are characterized by reaching of immune equilibrium independently to disease's activity. Together, these findings indicate that IL-10 is mainly produced during transient immune conditions and the persistent IL-10-related effect is the indication/prediction (and maybe effectuation) of the switching immunity. Actual knowledge emphasizes that any manipulation of the IL-10 response for treatment purposes should be considered very cautiously due to its potential hazards to the immune system. Probably, the IL-10 as potential switcher of immunity response should be used in association with co-stimulatory immune effectors that are necessary to determine the appropriate deviation during treatment of respective pathologies. Hopefully, further findings would open new avenues to study the biology of this "master switch" cytokine and its therapeutic potential.

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“…More recently, the existence of distinct stromal CB populations with different performances in vitro has been postulated, on the basis of their proliferative potential, colony-forming efficiency, and telomere length [21]. Fewer studies have comprehensively addressed the immunomodulatory properties of CB-MSC, exerted on several T cell subsets and NK cells, but also through inhibition of dendritic cell function [20, 22–25]. …”

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

Cited by 84 publications

References 62 publications

Double‐edged sword of mesenchymal stem cells: Cancer‐promoting versus therapeutic potential

Double‐edged sword of mesenchymal stem cells: Cancer‐promoting versus therapeutic potential

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response

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

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