ArticleBiological research2023
Spontaneous spheroids from alveolar bone-derived mesenchymal stromal cells maintain pluripotency of stem cells by regulating hypoxia-inducible factors.
Article in Biological research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 15 citations in OpenAlex.
- Microenvironment-mediated stem cell fate in periodontal tissue remodeling and repair.Bioactive materials · 2026Review
- Bone Organoids: A Novel Tool for Modeling and Managing Skeletal Disorders in Diabetes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mesenchymal Stromal/Stem Cell-Based Therapies for Liver Regeneration: Current Status and Future Directions.International journal of molecular sciences · 2026Review
- Bone regeneration using adipose derived stem cell spheroids within 3D printed scaffolds in a rabbit radial defect model.Scientific reports · 2025Article
- 3D culturing as a promising strategy to enhance the angiogenic potential of adipose stem cell-derived secretome: insights into the role of miR-145-5p/ANGPT2 axis.Stem cell research & therapy · 2025Article
- Effect of Octacalcium Phosphate on Osteogenic Differentiation of Induced Pluripotent Stem Cells in a 3D Hybrid Spheroid Culture.Biomimetics (Basel, Switzerland) · 2025Article
- Spheroid culture of human periodontal ligament stem cells on agarose enhances stemness and osteogenic differentiation potential.American journal of translational research · 2025Article
- High-Quality Three-Dimensionally Cultured Cells Using Interfaces of Diblock Copolymers Containing Different Ratios of ZwitterionicACS applied materials & interfaces · 2024Article
- Mesenchymal Stem Cell Spheroids: A Promising Tool for Vascularized Tissue Regeneration.Tissue engineering and regenerative medicine · 2024Review
- Mesenchymal Stromal Cells Derived from Dental Tissues: Immunomodulatory Properties and Clinical Potential.International journal of molecular sciences · 2024Review
- Regulation Mechanisms and Maintenance Strategies of Stemness in Mesenchymal Stem Cells.Stem cell reviews and reports · 2024Review
- Spheroids and organoids: Their implications for oral and craniofacial tissue/organ regeneration.Journal of oral biology and craniofacial researchArticle
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11 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundSpontaneous spheroid culture is a novel three-dimensional (3D) culture strategy for the rapid and efficient selection of progenitor cells. The objectives of this study are to investigate the pluripotency and differentiation capability of spontaneous spheroids from alveolar bone-derived mesenchymal stromal cells (AB-MSCs); compare the advantages of spontaneous spheroids to those of mechanical spheroids; and explore the mechanisms of stemness enhancement during spheroid formation from two-dimensional (2D) cultured cells.
methodsAB-MSCs were isolated from the alveolar bones of C57BL/6 J mice. Spontaneous spheroids formed in low-adherence specific culture plates. The stemness, proliferation, and multi-differentiation capacities of spheroids and monolayer cultures were investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, alkaline phosphatase (ALP) activity, and oil-red O staining. The pluripotency difference between the spontaneous and mechanical spheroids was analyzed using RT-qPCR. Hypoxia-inducible factor (HIFs) inhibition experiments were performed to explore the mechanisms of stemness maintenance in AB-MSC spheroids.
resultsAB-MSCs successfully formed spontaneous spheroids after 24 h. AB-MSC spheroids were positive for MSC markers and pluripotency markers (Oct4, KLF4, Sox2, and cMyc). Spheroids showed higher Ki67 expression and lower Caspase3 expression at 24 h. Under the corresponding conditions, the spheroids were successfully differentiated into osteogenic and adipogenic lineages. AB-MSC spheroids can induce neural-like cells after neurogenic differentiation. Higher expression of osteogenic markers, adipogenic markers, and neurogenic markers (NF-M, NeuN, and GFAP) was found in spheroids than in the monolayer. Spontaneous spheroids exhibited higher stemness than mechanical spheroids did. HIF-1α and HIF-2α were remarkably upregulated in spheroids. After HIF-1/2α-specific inhibition, spheroid formation was significantly reduced. Moreover, the expression of the pluripotency genes was suppressed.
conclusionsSpontaneous spheroids from AB-MSCs enhance stemness and pluripotency. HIF-1/2α plays an important role in the stemness regulation of spheroids. AB-MSC spheroids exhibit excellent multi-differentiation capability, which may be a potent therapy for craniomaxillofacial tissue regeneration.
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