Cited by 4,511Mesenchymal stem cell researchHematopoietic Stem Cell TransplantationImmunotherapy and Immune Responses

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Human mesenchymal stem cells modulate allogeneic immune cell responses

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Aggarwal, Sudeepta, Pittenger, Mark F.·2005·Blood

DOI 10.1182/blood-2004-04-1559

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Abstract

Mesenchymal stem cells (MSCs) are multipotent cells found in several adult tissues. Transplanted allogeneic MSCs can be detected in recipients at extended time points, indicating a lack of immune recognition and clearance. As well, a role for bone marrow-derived MSCs in reducing the incidence and severity of graft-versus-host disease (GVHD) during allogeneic transplantation has recently been reported; however, the mechanisms remain to be investigated. We examined the immunomodulatory functions of human MSCs (hMSCs) by coculturing them with purified subpopulations of immune cells and report here that hMSCs altered the cytokine secretion profile of dendritic cells (DCs), naive and effector T cells (T helper 1 [TH1] and TH2), and natural killer (NK) cells to induce a more anti-inflammatory or tolerant phenotype. Specifically, the hMSCs caused mature DCs type 1 (DC1) to decrease tumor necrosis factor α (TNF-α) secretion and mature DC2 to increase interleukin-10 (IL-10) secretion; hMSCs caused TH1 cells to decrease interferon γ (IFN-γ) and caused the TH2 cells to increase secretion of IL-4; hMSCs caused an increase in the proportion of regulatory T cells (TRegs) present; and hMSCs decreased secretion of IFN-γ from the NK cells. Mechanistically, the hMSCs produced elevated prostaglandin E2 (PGE2) in co-cultures, and inhibitors of PGE2 production mitigated hMSC-mediated immune modulation. These data offer insight into the interactions between allogeneic MSCs and immune cells and provide mechanisms likely involved with the in vivo MSC-mediated induction of tolerance that could be therapeutic for reduction of GVHD, rejection, and modulation of inflammation. (Blood. 2005;105:1815-1822)

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Archambault MP, McIntosh KR, Duty A, Peter SJ. Allogeneic rat mesenchymal stem cells do not elicit an immune response after implantation in immunocompetent recipients [abstract]. Blood.2000;96: 762a. Abstract 3295.

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Authors: Aggarwal, S., & Pittenger, M. F.
Affiliations: Osiris Therapeutics (United States) (US)
ORCID: Pittenger, Mark F.
Venue: Blood
Publisher: American Society of Hematology
Published: 2005-02-15
Volume: 105
Issue: 4
Pages: 1815-1822
ISSN: 0006-4971 (ISSN-L)
1528-0020
DOI: 10.1182/blood-2004-04-1559
OpenAlex: W2095666785
Cited by: 4,511
References: 73
Citations by year: 2026: 51 · 2025: 82 · 2024: 118 · 2023: 158 · 2022: 187 · 2021: 253 · 2020: 236 · 2019: 209 · 2018: 233 · 2017: 251 · 2016: 312 · 2015: 284 · 2014: 299 · 2013: 338 · 2012: 328
FWCI: 47.59
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Blood (publishedVersion)
PubMed (publishedVersion)
Funders: Osiris Therapeutics
Defense Advanced Research Projects Agency
Advanced Research Projects Agency
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords: mesenchymal stem cells, immunomodulation, graft-versus-host disease, allogeneic transplantation, dendritic cells, T helper cells, natural killer cells, regulatory T cells, prostaglandin E2, cytokine production, immune tolerance, bone marrow-derived stem cells
MeSH terms: Cell Communication, Cells, Cultured, Dendritic Cells, Humans, Immunologic Factors, Immunosuppression Therapy, Killer Cells, Natural, Leukocytes, Mononuclear, Lymphocyte Activation, Mesoderm, T-Lymphocytes, Transplantation, Homologous, Dinoprostone, Coculture Techniques, Multipotent Stem Cells

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Human mesenchymal stem cells modulate allogeneic immune cell responses

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