Stem cell therapies for degenerative cartilage disease are limited by an incomplete understanding of hyaline cartilage formation and maintenance. Human bone marrow stromal cells/skeletal stem cells (hBMSCs/SSCs) produce stable hyaline cartilage when attached to hyaluronic acid-coated fibrin microbeads (HyA-FMBs), yet the mechanism remains unclear. , hBMSC/SSC/HyA-FMB organoids exhibited reduced BMP signaling early in chondrogenic differentiation, followed by restoration of BMP signaling in chondrogenic / cells. Subsequently, human-induced pluripotent stem cell (hiPSC)-derived sclerotome cells were established (BMP inhibition) and then treated with transforming growth factor β (TGF-β) -/+ BMP2 and growth differentiation factor 5 (GDF5) (BMP signaling activation). TGF-β alone elicited a weak chondrogenic response, but TGF-β/BMP2/GDF5 led to delamination of aggregates (chondrospheroids) with high expression of , , and and minimal expression of and . While transplanted hBMSCs/SSCs/HyA-FMBs did not heal articular cartilage defects in immunocompromised rodents, chondrospheroid-derived cells/HyA-FMBs formed non-hypertrophic cartilage that persisted until at least 5 months .
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http://dx.doi.org/10.1016/j.isci.2024.110537 | DOI Listing |
Commun Biol
January 2025
Freie Universität Berlin, Institute for Chemistry and Biochemistry, Thielallee 63, 14195, Berlin, Germany.
Blood vessel formation relies on biochemical and mechanical signals, particularly during sprouting angiogenesis when endothelial tip cells (TCs) guide sprouting through filopodia formation. The contribution of BMP receptors in defining tip-cell characteristics is poorly understood. Our study combines genetic, biochemical, and molecular methods together with 3D traction force microscopy, which reveals an essential role of BMPR2 for actin-driven filopodia formation and mechanical properties of endothelial cells (ECs).
View Article and Find Full Text PDFStem Cells Int
December 2024
Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, China.
Biochim Biophys Acta Mol Basis Dis
January 2025
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China. Electronic address:
Adhesive arachnoiditis (AA) is a rare form of chronic degenerative pathology associated with persistent inflammation in the arachnoid matter of the spinal cord. Despite the existing knowledge, the detailed pathological mechanisms underlying AA are not fully understood. This study aimed to elucidate through comprehensive single nuclei RNA sequencing (snRNA-seq) to delineate the transcriptomic landscape of AA.
View Article and Find Full Text PDFNat Commun
January 2025
Biomimetic Systems for Cell Engineering Laboratory, Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain.
Intestinal epithelial cells are segregated into proliferative crypts and differentiated regions. This organization relies on specific signals, including Wnt3a, which regulates cell proliferation within crypts, and Eph/Ephrin, which dictates cell positioning along the crypt-villus axis. However, studying how the spatial distributions of these signals influences crypt-villus organization is challenging both in vitro and in vivo.
View Article and Find Full Text PDFNat Commun
January 2025
Institute for Regenerative Medicine, State Key Laboratory of Cardiology and Medical Innovation Center, Shanghai East Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai, 200092, China.
A balance between stem cell self-renewal and differentiation is required to maintain concurrent proliferation and cellular diversification in organoids; however, this has proven difficult in homogeneous cultures devoid of in vivo spatial niche gradients for adult stem cell-derived organoids. In this study, we leverage a combination of small molecule pathway modulators to enhance the stemness of organoid stem cells, thereby amplifying their differentiation potential and subsequently increasing cellular diversity within human intestinal organoids without the need for artificial spatial or temporal signaling gradients. Moreover, we demonstrate that this balance between self-renewal and differentiation can be effectively and reversibly shifted from secretory cell differentiation to the enterocyte lineage with enhanced proliferation using BET inhibitors, or unidirectional differentiation towards specific intestinal cell types by manipulating in vivo niche signals such as Wnt, Notch, and BMP.
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