Administration of bone marrow-derived mesenchymal stem cells (MSCs) is a possible treatment for graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation and other inflammatory conditions. To address the mechanism of immunosuppression by MSCs, in particular those derived from adipose tissue (AMSCs), AMSCs were isolated from three different mouse strains, and the suppressive capacity of the AMSCs thus obtained to suppress interferon (IFN)-γ generation in mixed lymphocyte reaction cultures serving as an model of GVHD were assessed. It was revealed that the AMSCs had a potent capacity to suppress IFN-γ production regardless of their strain of origin and that such suppression was not associated with production of interleukin-10. In addition, the results demonstrated that β2-microglobulin (β2m)-deficient AMSCs from β2m mice were also potent suppressor cells, verifying the fact that the mechanism underlying the suppression by AMSCs is independent of major histocompatibility complex (MHC) class I expression or MHC compatibility. As AMSCs appear to have immunosuppressive properties, AMSCs may be a useful source of biological suppressor cells for the control of GVHD in humans.
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http://dx.doi.org/10.3892/etm.2018.6689 | DOI Listing |
STAR Protoc
January 2025
Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305, USA; Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA. Electronic address:
Hematopoietic stem cells (HSCs) generate blood and immune cells. Here, we present a protocol to differentiate human pluripotent stem cells (hPSCs) into hematopoietic progenitors that express the signature HSC transcription factors HLF, HOXA5, HOXA7, HOXA9, and HOXA10. hPSCs are dissociated, seeded, and then sequentially differentiated into posterior primitive streak, lateral mesoderm, artery endothelium, hemogenic endothelium, and hematopoietic progenitors through the sequential addition of defined, serum-free media.
View Article and Find Full Text PDFCytotherapy
January 2025
Osteoarthritis Research Program, Division of Orthopedic Surgery, Schroeder Arthritis Institute, University Health Network, Toronto, Ontario, Canada; Krembil Research Institute, University Health Network, Toronto, Ontario, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, Division of Hematology, University of Toronto, Toronto, Ontario, Canada. Electronic address:
The December 2024 US Food and Drug Administration (FDA) approval of Mesoblast's Ryoncil (remestemcel-L-rknd)-allogeneic bone marrow mesenchymal stromal cell (MSC(M)) therapy-in pediatric acute steroid-refractory graft-versus-host-disease finally ended a long-lasting drought on approved MSC clinical products in the United States. While other jurisdictions-including Europe, Japan, India, and South Korea-have marketed autologous or allogeneic MSC products, the United States has lagged in its approval. The sponsor's significant efforts and investments, working closely with the FDA addressing concerns regarding clinical efficacy and consistent MSC potency through an iterative process that spanned several years, was rewarded with this landmark approval.
View Article and Find Full Text PDFCell Biosci
January 2025
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong S.A.R., China.
Background: Pathogenic or null mutations in WRN helicase is a cause of premature aging disease Werner syndrome (WS). WRN is known to protect somatic cells including adult stem cells from premature senescence. Loss of WRN in mesenchymal stem cells (MSCs) not only drives the cells to premature senescence but also significantly impairs the function of the stem cells in tissue repair or regeneration.
View Article and Find Full Text PDFJ Adv Res
January 2025
Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, National Clinical Research Center for Oral Diseases, 22 Zhongguancun South Avenue, Beijing 100081, China. Electronic address:
Introduction: Periodontal diseases are prevalent among middle-aged and elderly individuals. There's still no satisfactory solution for tooth loss caused by periodontal diseases. Human periodontal ligament stem cells (hPDLSCs) is a distinctive subgroup of mesenchymal stem cells, which play a crucial role in periodontal supportive tissues, but their application value hasn't been fully explored yet.
View Article and Find Full Text PDFJ Bone Miner Res
January 2025
NHC Key Lab of Hormones and Development, Tianjin Key Lab of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China.
Epiregulin plays a role in a range of biological activities including malignancies. This study aims to investigate the potential contribution of epiregulin to bone cell differentiation and bone homeostasis. The data showed that epiregulin expression was upregulated during osteogenesis but downregulated during adipogenesis.
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