A study on mutual interaction between cytokine induced killer cells and umbilical cord-derived mesenchymal cells: Implication for their in-vivo use

Chieregato, Katia; Albiero, Elena; Castegnaro, Silvia; Bernardi, M.; dʼAmore, Emanuele S.G.; Zanon, Cristina; Madeo, Domenico; Rodeghiero, Francesco; Astori, Giuseppe

doi:10.1016/j.bcmd.2012.05.009

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…AT- and UC-derived MSC were isolated as described previously by our group [ 18 , 19 ]. Fresh UC was collected from the Obstetrics and Gynecology Unit of S. Bortolo Hospital (Vicenza, Italy) from full-term deliveries after cesarean section.…”

Section: Methodsmentioning

confidence: 99%

High-throughput immunophenotypic characterization of bone marrow- and cord blood-derived mesenchymal stromal cells reveals common and differentially expressed markers: identification of angiotensin-converting enzyme (CD143) as a marker differentially expressed between adult and perinatal tissue sources

Amati

Perbellini

Rotta³

et al. 2018

Stem Cell Res Ther

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BackgroundMesenchymal stromal cells (MSC) are a heterogeneous population of multipotent progenitors used in the clinic because of their immunomodulatory properties and their ability to differentiate into multiple mesodermal lineages. Although bone marrow (BM) remains the most common MSC source, cord blood (CB) can be collected noninvasively and without major ethical concerns. Comparative studies comprehensively characterizing the MSC phenotype across several tissue sources are still lacking. This study provides a 246-antigen immunophenotypic analysis of BM- and CB-derived MSC aimed at identifying common and strongly expressed MSC markers as well as the existence of discriminating markers between the two sources.MethodsBM-MSC (n = 4) were expanded and analyzed as bulk (n = 6) or single clones isolated from the bulk culture (n = 3). CB-MSC (n = 6) were isolated and expanded as single clones in 5/6 samples. The BM-MSC and CB-MSC phenotype was investigated by flow cytometry using a panel of 246 monoclonal antibodies. To define the markers common to both sources, those showing the smallest variation between samples (coefficient of variation of log2 fold increase ≤ 0.5, n = 59) were selected for unsupervised hierarchical cluster analysis (HCL). Differentially expressed markers were identified by directly comparing the expression of all 246 antigens between BM-MSC and CB-MSC.ResultsBased on HCL, 18 markers clustered as strongly expressed in BM-MSC and CB-MSC, including alpha-smooth muscle antigen (SMA), beta-2-microglobulin, CD105, CD13, CD140b, CD147, CD151, CD276, CD29, CD44, CD47, CD59, CD73, CD81, CD90, CD98, HLA-ABC, and vimentin. All except CD140b and alpha-SMA were suitable for the specific identification of ex-vivo expanded MSC. Notably, only angiotensin-converting enzyme (CD143) was exclusively expressed on BM-MSC. CD143 expression was tested on 10 additional BM-MSC and CB-MSC and on 10 umbilical cord- and adipose tissue-derived MSC samples, confirming that its expression is restricted to adult sources.ConclusionsThis is the first study that has comprehensively compared the phenotype of BM-MSC and CB-MSC. We have identified markers that could complement the minimal panel proposed for the in-vitro MSC definition, being shared and strongly expressed by BM- and CB-derived MSC. We have also identified CD143 as a marker exclusively expressed on MSC derived from adult tissue sources. Further studies will elucidate the biological role of CD143 and its potential association with tissue-specific MSC features.Electronic supplementary materialThe online version of this article (doi:10.1186/s13287-017-0755-3) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

High-throughput immunophenotypic characterization of bone marrow- and cord blood-derived mesenchymal stromal cells reveals common and differentially expressed markers: identification of angiotensin-converting enzyme (CD143) as a marker differentially expressed between adult and perinatal tissue sources

Amati

Perbellini

Rotta³

et al. 2018

Stem Cell Res Ther

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“…UC-MSCs were also cultured in human umbilical cord blood low enriched plasma, (CP), supplemented with EGF and FGF2; these cells are referred to as UC-MSC (CP) within the text. CP was prepared following a protocol modified from Chieregato et al 44 . Briefly, CP was thawed at 37 °C to promote cell disruption.…”

Section: Methodsmentioning

confidence: 99%

MHC-class-II are expressed in a subpopulation of human neural stem cells in vitro in an IFNγ–independent fashion and during development

Vagaska¹,

New²,

Alvarez-Gonzalez

et al. 2016

Sci Rep

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Expression of major histocompatibility antigens class-2 (MHC-II) under non-inflammatory conditions is not usually associated with the nervous system. Comparative analysis of immunogenicity of human embryonic/fetal brain-derived neural stem cells (hNSCs) and human mesenchymal stem cells with neurogenic potential from umbilical cord (UC-MSCs) and paediatric adipose tissue (ADSCs), while highlighting differences in their immunogenicity, led us to discover subsets of neural cells co-expressing the neural marker SOX2 and MHC-II antigen in vivo during human CNS development. MHC-II proteins in hNSCs are functional, and differently regulated upon differentiation along different lineages. Mimicking an inflammatory response using the inflammatory cytokine IFNγ induced MHC-II up-regulation in both astrocytes and hNSCs, but not in UC-MSCs and ADSCs, either undifferentiated or differentiated, though IFNγ receptor expression was comparable. Together, hypoimmunogenicity of both UC-MSCs and ADSCs supports their suitability for allogeneic therapy, while significant immunogenicity of hNSCs and their progeny may at least in part underlie negative effects reported in some patients following embryonic neural cell grafts. Crucially, we show for the first time that MHC-II expression in developing human brains is not restricted to microglia as previously suggested, but is present in discrete subsets of neural progenitors and appears to be regulated independently of inflammatory stimuli.

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“…Till now, few studies have been performed to address the interaction between MSC and CIK cells in vivo and vitro. Recently, Chieregato et al () reported that CB‐derived MSC significantly suppressed CIK cells in a dose‐dependent manner after co‐culture and CIK cells can lyse UC‐MSC mildly in a ratio‐dependent manner, but the underlying mechanism of immune suppressive activity of MSC on CIK cells whether or not like that on T or NK cells is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Bone marrow mesenchymal stem cells suppressing activation of allogeneic cytokine‐induced killer/natural killer cells either by direct or indirect interaction

Yang

et al. 2015

Cell Biology International

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Bone marrow mesenchymal stem cells (MSC) were recently found to be associated with some special immunological characteristics, the immunoregulatory effect of MSC was dose-dependent. Low amount of MSC was associated with mild immunosuppression or even immune activation, while the high amount of that was associated with significant immunosuppressive effect. In this study, by using a transwell system, we explored the effect of MSC on the cell cycle, apoptosis rate and the expression of CD69, an activation marker, on the allogeneic cord blood derived cytokine-induced killer(CIK)/natural killer(NK) cells. The results showed that either by transwell or mixed cell-cell co-culture, the MSC can effect CIK/NK cells on the cell cycle, such as arrested in the G0/G1 phase, diminished the ratio of cells in S, G2/M phase, and increased the apoptosis of them. MSC can also depress the expression of CD69 on these killer cells, as well as increased the ratio of CD4(+) CD25(+) CD127(low) T regulatory (Treg) cells in the CIK/NK cell culture system. We draw conclusions that either by transwell or mixed co-culture, the MSC can suppress activation of allogeneic CB-CIK/NK cells in a dose-dependent manner.

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A study on mutual interaction between cytokine induced killer cells and umbilical cord-derived mesenchymal cells: Implication for their in-vivo use

Cited by 10 publications

References 39 publications

MHC-class-II are expressed in a subpopulation of human neural stem cells in vitro in an IFNγ–independent fashion and during development

Bone marrow mesenchymal stem cells suppressing activation of allogeneic cytokine‐induced killer/natural killer cells either by direct or indirect interaction

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