Aim: To evaluate the early hematopoietic reconstitution of implanted SCID mice which were transplanted with human umbilical cord blood-derived mononuclear cells (UCB-MNC) and placenta-derived mesenchymal stem cells (PMSC) by intro-bone marrow injection (IBMI).
Methods: The placenta tissues were digested by collagenase IV and cultured with low-glucose DMEM supplemented with b-FGF. The adherent cells were collected and passaged. The phenotypes of the cultured cells were detected by flow cytometry. The osteogenic differentiation and adipogenic differentiation were induced and detected. SCID recipient mice conditioned with sublethal dose irradiation were transplanted with human UCB-MNC and PMSC by IBMI or intravenous injection (IV). Fifty recipient mice were divided into five groups at random: cotransplantation group A (PMSC+UCB-MNC by IBMI), single transplantation group B (UCB-MNC by IBMI), cotransplantation group C (PMSC by IBMI, UCB-MNC by IV), normal saline control group D (normal saline by IBMI), normal control group E (normal saline by IBMI). There were ten recipient mice in every group. On day 14, the bone marrow cells of every recipient mouse were flushed out from the injected tibias and contralateral tibias, respectively. The percentage of human CD34+ and CD45+ hematopoietic cells was analyzed by flow cytometry.
Results: PMSC were isolated and expanded from human placenta, which were successfully induced to osteogenic differentiation and adipogenic differentiation. FACS analyses showed that the phenotypes of PMSC were normal. On day 14 after transplantation in SCID mice, the percentages of human CD34+ and CD45+ hematopoietic cells in the tibias of group B were both significantly lower than them in the injected tibias and contralateral tibias of group A.
Conclusion: Human PMSC could enhance the early engraftment of UCB-MNC in SCID mice.
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Lab Anim Res
December 2024
Department of Experimental Animal Research, Biomedical Research Institute, Seoul National Univ. Hospital, Seoul, Korea.
Background: Genetically immunodeficient mice lacking Il2rg and Rag2 genes have been widely utilized in the field of biomedical research. However, immunodeficient rats, which offer the advantage of larger size, have not been as extensively used to date. Recently, Severe Combined Immunodeficiency (SCID) rats were generated using CRISPR/Cas9 system, targeting Il2rg and Rag2 in National BioResource Project in Japan.
View Article and Find Full Text PDFLiver Int
January 2025
Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy.
Background & Aims: GD2, a member of the ganglioside (GS) family (sialic acid-containing glycosphingolipids), is a potential biomarker of cancer stem cells (CSC) in several tumours. However, the possible role of GD2 and its biosynthetic enzyme, GD3 synthase (GD3S), in intrahepatic cholangiocarcinoma (iCCA) has not been explored.
Methods: The stem-like subset of two iCCA cell lines was enriched by sphere culture (SPH) and compared to monolayer parental cells (MON).
Front Immunol
December 2024
Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Introduction: Extracellular vesicles of Natural Killer cells (NKEV) exert an antitumor effect towards hematopoietic and solid tumors and have an immune modulating effect, suggesting a promising role in immune and biotherapy. In this study, a continuation of our former works, we demonstrated a network by mass spectrometry analysis between NKEV protein cargo and antitumor effects. Human healthy NKEV, both exosomes and microvesicles, have a significant and direct cytotoxic effect against human B cell lymphoma in and conditions.
View Article and Find Full Text PDFMol Metab
December 2024
Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy. Electronic address:
By analyzing RNA datasets from rhabdomyosarcoma (RMS), a soft tissue tumor with a prevalence in young people, we found upregulation of sterol regulatory element-binding protein 2 (SREBP2) and mevalonate pathway (MVP) genes, including 3-Hydroxy-3-Methylglutaryl-CoA Reductase (HMGCR), farnesyl-diphosphate synthase (FDPS), squalene epoxidase (SQLE), which correlated with worse overall patient survival and predicted statin sensitivity. In human RD and RH30 lines, treatment with 0.01-1 μM doses of fatostatin (SREBP2 inhibitor), lovastatin and simvastatin (HMGCR inhibitors), and zoledronic acid (FDPS inhibitor) impaired cell growth and migration, which were conversely stimulated by 50-100 μM cholesterol (CHO) supplementation.
View Article and Find Full Text PDFJ Hematol Oncol
December 2024
Department of Onco-Haematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, San Paolo N°15 Street, 00146, Rome, Italy.
Sarcomas are rare, mesenchymal tumors, representing about 10-15% of all childhood cancers. GD2 is a suitable target for chimeric antigen receptor (CAR) T-cell therapy due to its overexpression in several solid tumors. In this preclinical study, we investigated the potential use of iCasp9.
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