Molecular mechanisms governing cell fate decision events in bone marrow mesenchymal stromal cells (MSC) are still poorly understood. Herein, we investigated the homeobox gene as a candidate regulatory molecule, by adopting hypomorphic mice as a model to investigate the effects of downregulation, using in vitro and in vivo assays, including the innovative single cell RNA sequencing technology. Taken together, our findings indicate that low levels of are associated to enhanced adipogenesis and a concomitant reduced osteogenesis in the bone marrow, suggesting Prep1 as a potential regulator of the adipo-osteogenic differentiation of mesenchymal stromal cells. Furthermore, our data suggest that in vivo decreased gene dosage favors a pro-adipogenic phenotype and induces a "browning" effect in all fat tissues.
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http://dx.doi.org/10.3390/ijms20153639 | DOI Listing |
Pharmaceutics
December 2024
Laboratorio RAMSES, IRCCS Istituto Ortopedico Rizzoli, Via di Barbiano, 1/10, 40136 Bologna, Italy.
The treatment of articular cartilage damage has always represented a problem of considerable practical interest for orthopedics. Over the years, many surgical techniques have been proposed to induce the growth of repairing tissue and limit degeneration. In 1994, the turning point occurred: implanted autologous cells paved the way for a new treatment option based more on regeneration than repair.
View Article and Find Full Text PDFPharmaceutics
December 2024
Sports Medicine Division, Institute of Orthopedics and Traumatology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 05403-010, SP, Brazil.
Background/objectives: Cartilage injuries and osteoarthritis are prevalent public health problems, due to their disabling nature and economic impact. Mesenchymal stromal cells (MSCs) isolated from different tissues have the immunomodulatory capacity to regulate local joint environment. This translational study aims to compare cartilage restoration from MSCs from the synovial membrane (SM) and dental pulp (DP) by a tissue-engineered construct with Good Manufacturing Practices.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Division of Trauma & Orthopaedic Surgery, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 0QQ, UK.
Mesenchymal stromal cells (MSCs) have the potential for novel treatments of several musculoskeletal conditions due to their ability to differentiate into several cell lineages including chondrocytes, adipocytes and osteocytes. Researchers are exploring whether this could be utilized for novel therapies for joint afflictions. The role of gender in the ability of MSCs to differentiate and proliferate into different cells has not been clearly defined.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Neural Regenerative Medicine, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Hokkaido, Japan.
Spinal cord injury (SCI) disrupts the blood-spinal cord barrier (BSCB) exacerbating damage by allowing harmful substances and immune cells to infiltrate spinal neural tissues from the vasculature. This leads to inflammation, oxidative stress, and impaired axonal regeneration. The BSCB, essential for maintaining spinal cord homeostasis, is structurally similar to the blood-brain barrier.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
National Medical Research Center of Cardiology Named after Academician E.I. Chazov, Moscow 121552, Russia.
Constructing artificial tertiary lymphoid structures (TLSs) opens new avenues for advancing cancer immunotherapy and personalized medicine by creating controllable immune niches. Mesenchymal stromal cells (MSCs) offer an ideal stromal source for such constructs, given their potent immunomodulatory abilities and accessibility. In this study, we explored the potential of adipose-derived MSCs to adopt TLS-supportive phenotypes and facilitate lymphocyte organization.
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