Bone marrow derived-mesenchymal stromal cells (BM-MSCs) are multipotent, nonhematopoietic progenitors in a hematopoietic microenvironment and indispensable for regulating hematopoiesis. Several studies have reported that toll-like receptors (TLRs) are expressed in mesenchymal stromal cells (MSCs) to modulate their biological functions. In this study, we investigated the possible role(s) of TLRs in mediating the hematopoiesis-supporting role of human BM-MSCs. Human BM-MSCs were analyzed for mRNA expression of TLR1-10 by reverse transcription-polymerase chain reaction. TLR1-6, but not TLR7-10 were expressed by BM-MSCs. The protein expression of TLR2 and TLR4 was also confirmed by flow cytometry. We further explored the role of TLR2 and TLR4 in mediating the capacity of BM-MSCs to support the proliferation and differentiation of CD34(+) hematopoietic stem/progenitor cells obtained from cord blood. BM-MSCs increased proliferation of CD34(+) cells and promoted the differentiation towards the myeloid lineage 7 or 14days after co-culture, as well as colony formation by those cells and the production of interleukin 1 (IL-1), IL-8, IL-11, stem cell factor (SCF), granulocyte colony-stimulating factor (CSF), macrophage CSF and granulocyte-macrophage CSF, if MSCs had been stimulated with TLR2 agonist (PAM(3)CSK(4)) or TLR4 agonist (LPS). Interestingly, although these effects were elevated in a different degree, a synergistic effect was not observed in BM-MSCs co-stimulated with PAM(3)CSK(4) and LPS. Together, our findings suggest that TLR2 and TLR4 signaling may indirectly regulate hematopoiesis by modulating BM-MSCs' functions. The increased hematopoietic proliferation and differentiation could be mediated, at least in part, by augmented hematopoiesis-related cytokine production of BM-MSCs.
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http://dx.doi.org/10.1016/j.yexcr.2011.11.001 | DOI Listing |
Mol Biol Rep
January 2025
Pediatric Cell, and Gene Therapy Research Center Gene, Cell and Tissue Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Bone serves as a fundamental structural component in the body, playing pivotal roles in support, protection, mineral supply, and hormonal regulation. However, critical-sized bone injuries have become increasingly prevalent, necessitating extensive medical interventions due to limitations in the body's capacity for self-repair. Traditional approaches, such as autografts, allografts, and xenografts, have yielded unsatisfactory results.
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Department of Obstetrics and Gynecology, Lishui Municipal Central Hospital, Lishui, Zhejiang, 323000, China.
Background: Endometriosis (EMS) is a difficult gynecological disease to cure. Frizzled-7 (FZD7) has been shown to be associated with the development of EMS, but its specific mechanism remains unclarified. This study aims to explore the role of FZD7 in EMS.
View Article and Find Full Text PDFJ Biomed Mater Res B Appl Biomater
January 2025
The Laboratory of Orthopaedic Tissue Regeneration & Orthobiologics, Department of Bioengineering, Clemson University, Clemson, South Carolina, USA.
The formation of fibrocartilage in microfracture (MFX) severely limits its long-term outlook. There is consensus in the scientific community that the placement of an appropriate scaffold in the MFX defect site can promote hyaline cartilage formation and improve therapeutic benefit. Accordingly, in this work, a novel natural biomaterial-the cartilage analog (CA)-which met criteria favorable for chondrogenesis, was evaluated in vitro to determine its candidacy as a potential MFX scaffold.
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January 2025
Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain oxidative phosphorylation (OXPHOS). While this metabolic program produces adequate biosynthetic intermediates, reducing agents, ATP, and epigenetic remodeling cofactors necessary to sustain growth, it also produces large amounts of byproducts that can generate a hostile tumor microenvironment (TME) characterized by low pH, redox stress, and poor oxygenation.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
College of Life Science, Northeast Forestry University, Harbin 150040, China.
Melanoma is among the most common malignancies and has recently exhibited increased resistance to treatments, resulting in a more aggressive disease course. Mesenchymal stem cells (MSCs) secrete cytokines both in vivo and in vitro, which regulate tumor cell signaling pathways and the tumor microenvironment, thereby influencing tumor progression. This study investigates the anti-melanogenesis effects of sheep umbilical cord mesenchymal stem cells (SUCMSCs) to assess their potential application in melanoma treatment.
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