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Cited by 3,226Mesenchymal stem cell researchHematopoietic Stem Cell TransplantationT-cell and B-cell Immunology

Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli

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Di Nicola, Massimo, Carlo-Stella, Carmelo, Magni, Michele, Milanesi, Marco, Longoni, Paolo D., Matteucci, Paola, Grisanti, Salvatore, Gianni, Alessandro M.·2002·Blood
DOI 10.1182/blood.v99.10.3838
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Abstract

CD2+ T lymphocytes obtained from either the donor of bone marrow stromal cells (BMSCs) or a third party were cultured in mixed lymphocyte reactions (MLRs) with either allogeneic dendritic cells (DCs) or peripheral blood lymphocytes (PBLs). When autologous or allogeneic BMSCs were added back to T cells stimulated by DCs or PBLs, a significant and dose-dependent reduction of T-cell proliferation, ranging from 60% ± 5% to 98% ± 1%, was evident. Similarly, addition of BMSCs to T cells stimulated by polyclonal activators resulted in a 65% ± 5% (P = .0001) suppression of proliferation. BMSC- induced T-cell suppression was still evident when BMSCs were added in culture as late as 5 days after starting of MLRs. BMSC-inhibited T lymphocytes were not apoptotic and efficiently proliferated on restimulation. BMSCs significantly suppressed both CD4+ and CD8+ T cells (65% ± 5%, [P = .0005] and 75% ± 15% [P = .0005], respectively). Transwell experiments, in which cell-cell contact between BMSCs and effector cells was prevented, resulted in a significant inhibition of T-lymphocyte proliferation, suggesting that soluble factors were involved in this phenomenon. By using neutralizing monoclonal antibodies, transforming growth factor β1 and hepatocyte growth factor were identified as the mediators of BMSC effects. In conclusion, our data demonstrate that (1) autologous or allogeneic BMSCs strongly suppress T-lymphocyte proliferation, (2) this phenomenon that is triggered by both cellular as well as nonspecific mitogenic stimuli has no immunologic restriction, and (3) T-cell inhibition is not due to induction of apoptosis and is likely due to the production of soluble factors.

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Crossref · 10.1182/blood.v99.10.3838

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  • The immunomodulatory capabilities of MSCs are not intrinsic and constitutive, but are rather licensed or triggered by inflammatory cytokines and influenced by the type and status of inflammation.

    “In contrast with preceding concepts, studies have revealed that the immunomodulatory capabilities of MSCs are not intrinsic and constitutive, but are rather licensed or triggered by inflammatory cytokines and influenced by the type and status of inflammation [131, 132].”

    From Mechanisms, efficacy, and future perspectives of cellular-based therapies for liver fibrosis/cirrhosis: focusing on mesenchymal stromal cells (2025) · cites this paper as [132]

    The Discussion reports that bone marrow stromal cells suppress T-cell proliferation and that stromal-cell-derived cytokines mediate the effect. It does not show that inflammatory cytokines license or trigger the stromal cells’ immunomodulatory capability, or that the type and status of inflammation determine it. The stimuli described in the Discussion trigger T-cell proliferation, not stromal-cell licensing. (LLM, conf=0.81)

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  • Once activated, mesenchymal stromal cells produce molecules (TGF-b1, HGF, IDO, PGE2) that inhibit lymphocyte proliferation and suppress the immune function of T lymphocytes, dendritic cell maturation/differentiation, and NK and B-cell activation.

    “Once MSCs are activated, they produce a number of molecules (namely TGF-b1, HGF, IDO, PGE2) that inhibit lymphocyte proliferation and suppress the immune function of T lymphocytes, dendritic cell maturation/differentiation, and NK and B-cell activation; simultaneously, MSCs increase the production of regulatory T-cells using a contact-dependent mechanism or by secreting IL-10 and TGF-b, [37], [38]”

    From Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice (2019) · cites this paper as [38]

    Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

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  • Mesenchymal stromal cells increase the production of regulatory T-cells using a contact-dependent mechanism or by secreting IL-10 and TGF-b.

    “simultaneously, MSCs increase the production of regulatory T-cells using a contact-dependent mechanism or by secreting IL-10 and TGF-b, [37], [38], [39], [40], [41].”

    From Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice (2019) · cites this paper as [38]

    The Discussion (page unavailable) reports that bone marrow stromal cells suppress T-cell proliferation and that TGF-β1 contributes to this effect. It does not report increased production of regulatory T cells or identify IL-10 as a mediator. Its contact experiment found that cell contact was not required for the suppression studied, although suppression was stronger when contact was allowed. (LLM, conf=0.86)

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Research works printed but not linked: 8

  1. [3]3. Bruder SP, Jaiswal N, Haynesworth SE. Growth ki- netics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during ex- tensive subcultivation and following cryopreserva- tion. J Cell Biochem. 1997;64:278-294.
  2. [7]7. Johnstone B, Hering TM, Caplan AI, Goldberg VM, Yoo JU. In vitro chondrogenesis of bone mar- row-derived mesenchymal progenitor cells. Exp Cell Res. 1998;238:265-272.
  3. [10]10. Almeida-Porada G, Porada CD, Tran N, Zanjani ED. Cotransplantation of human stromal cell pro- genitors into preimmune fetal sheep results in early appearance of human donor cells in circula- tion and boosts cell levels in bone marrow at later time points after transplantation. Blood. 2000;95: 3620-3627.
  4. [23]23. Bartholomew A, Sturgeon C, Siatkas M, et al. Mes- enchymal stem cells can prolong skin graft survival in the baboon [abstract]. Blood. 1999;94:135.
  5. [25]25. Klyshnenkova E, Shustova V, Mosca J, et al. Human mesenchymal stem cells induce unresponsiveness in preactivated but not naive alloantigen specific T cells [abstract]. Exp Hematol. 1999;27:122.
  6. [27]27. Majumdar MK, Thiede MA, Mosca JD, Moorman M, Gerson SL. Phenotypic and functional com- parison of cultures of marrow-derived mesenchy- mal stem cells (MSCs) and stromal cells. J Cell Physiol. 1998;176:57-66.
  7. [28]28. Novelli E, Buyaner D, Chopra R, et al. Human mesenchymal stem cells can enhance human CD34 ϩ cells repopulating of NOD/SCID mice [abstract]. Blood. 1998;92:664.
  8. [30]30. Lazarus H, Curtin P, Devine S, et al. Role of mes- enchymal stem cells (MSC) in allogeneic trans- plantation: early phase I clinical results [abstract]. Blood. 2000;392:1691.

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Authors
Di Nicola, M., Carlo-Stella, C., Magni, M., Milanesi, M., Longoni, P. D., Matteucci, P., Grisanti, S., & Gianni, A. M.
Affiliations
  • From the “Cristina Gandini” Bone Marrow Transplantation Unit, Istituto Nazionale Tumori, Milano, Italy; and Chair of Oncology, University of Milano, Milano, Italy.
  • University of Milan (IT)
ORCID
Venue
Blood
Publisher
American Society of Hematology
Published
2002-05-15
Volume
99
Issue
10
Pages
3838-3843
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood.v99.10.3838
OpenAlex
W2159358845
Cited by
3,226
References
36
Citations by year
2026: 34 · 2025: 37 · 2024: 57 · 2023: 91 · 2022: 115 · 2021: 149 · 2020: 145 · 2019: 151 · 2018: 158 · 2017: 165 · 2016: 217 · 2015: 196 · 2014: 206 · 2013: 254 · 2012: 222
FWCI
21.22
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion, public-domain)
Funders
Associazione Italiana per la Ricerca sul Cancro
Topics
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
mesenchymal stem cells, T cell suppression, T cell proliferation, mixed lymphocyte reaction, dendritic cells, mitogen stimulation, soluble factors, TGF-β1, hepatocyte growth factor, CD4+ T cells, CD8+ T cells, cell-cell contact, immunomodulation
MeSH terms
Antibodies, Monoclonal, Bone Marrow Cells, Cells, Cultured, Dendritic Cells, Humans, Kinetics, Lymphocyte Culture Test, Mixed, Lymphocyte Activation, Mitogens, T-Lymphocytes, CD4-Positive T-Lymphocytes, Cytokines, Stromal Cells, Apoptosis, CD8-Positive T-Lymphocytes, Coculture Techniques

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