The epigenetic modifications during the transdifferentiation of adult stem cells remain to be fully elucidated. In the present study, the histone H3 modifications during the transdifferentiation of rat Thy‑1(+) Lin(‑) bone marrow cells into hepatocytes in vitro were examined, which involved performing hepatocyte growth factor-mediated transdifferentiation of bone marrow Thy-1(+) Lin(‑) cells into hepatic lineage cells. Subsequently, the hepatocyte-specific markers, cytokeratin‑18 (CK‑18), albumin (ALB) and α‑fetoprotein (AFP) were examined by immunofluorescence staining or reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Changes in the key pluripotency factor, octamer‑binding transcription factor 4 (OCT4) and histone modifications, including the dimethylation and acetylation of H3 at lysine 9 (H3K9me2 and H3K9ac), lysine 14 (H3K14me2 and H3K14ac) and lysine 27 (H3K27me2 and H3K27ac), were also investigated by RT-qPCR, immunofluorescence staining or western blot analysis The mRNA expression levels of AFP and ALB were detected in the bone marrow stem cell‑derived hepatic lineage cells on days 7 and 14 following induction, and CK‑18 was detected on day 14 following induction. During the transdifferentiation of the bone marrow Thy‑1(+) Lin(‑) cells into hepatocytes, the mRNA expression of OCT4 was significantly reduced, and the levels of H3K9me2, H3K9ac, H3K14me2, H3K14ac, H3K27me2 and H3K27ac were increased significantly, compared with the levels at baseline (P<0.05). Therefore, the results of the present study demonstrated that histone H3 modifications at lysine 9, 14 and 27 are involved in the regulation of transcription during the transdifferentiation of bone marrow stem cells to hepatic lineage cells.
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http://dx.doi.org/10.3892/mmr.2015.4384 | DOI Listing |
Cytotherapy
January 2025
Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. Electronic address:
Background/aims: Human mesenchymal stromal cells (hMSC) are multipotent adult cells commonly used in regenerative medicine as advanced therapy medicinal products. The expansion of these cells in xeno-free supplements is highly encouraged by regulatory agencies due to safety concerns. However, the number of supplements with robust performance and consistency for hMSC expansion are limited.
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 PDFBone Marrow Transplant
January 2025
Université de Franche-Comté, EFS, INSERM, UMR RIGHT, F-, 25000, Besançon, France.
The accessibility of CAR-T cells in centralized production models faces significant challenges, primarily stemming from logistical complexities and prohibitive costs. However, European Regulation EC No. 1394/2007 introduced a pivotal provision known as the hospital exemption.
View Article and Find Full Text PDFNat Commun
January 2025
Type 2 Immunity Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, MD, USA.
How macrophages in the tissue environment integrate multiple stimuli depends on the genetic background of the host, but this is still poorly understood. We investigate IL-4 activation of male C57BL/6 and BALB/c strain specific in vivo tissue-resident macrophages (TRMs) from the peritoneal cavity. C57BL/6 TRMs are more transcriptionally responsive to IL-4 stimulation, with induced genes associated with more super enhancers, induced enhancers, and topologically associating domains (TAD) boundaries.
View Article and Find Full Text PDFJ Clin Lipidol
December 2024
Internal Medicine Department, Coimbra's Healthcare Integrated Delivery System, Praceta Professor Mota Pinto, 3004-561, Coimbra, Portugal.
Tangier disease is an extremely rare autosomal recessive monogenic disorder caused by mutations in the ATP binding cassette transporter A1 gene (ABCA1). It is characterized by severe deficiency or absence of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA1), with highly variable clinical presentations depending on cholesterol accumulation in macrophages across different tissues. We report a case of a 47-year-old man with very low HDL-C and very high triglyceride levels, initially attributed to the patient's metabolic syndrome, alcohol abuse, and splenomegaly.
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