AI Article Synopsis

  • Stem cell therapies for cartilage disease are hindered by a lack of understanding of cartilage formation and maintenance.
  • Human bone marrow stromal cells (hBMSCs) can create stable cartilage when using hyaluronic acid-coated microbeads, but the exact mechanisms are not fully understood.
  • Although hBMSCs failed to repair cartilage in rodents, cells derived from chondrospheroids showed promising results by forming lasting non-hypertrophic cartilage.

Article Abstract

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 .

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347861PMC
http://dx.doi.org/10.1016/j.isci.2024.110537DOI Listing

Publication Analysis

Top Keywords

bmp signaling
16
stem cell
8
hyaline cartilage
8
bmp
5
cartilage
5
time- cell-specific
4
cell-specific activation
4
activation bmp
4
signaling
4
signaling restrains
4

Similar Publications

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 PDF

Noggin Combined With Human Dental Pulp Stem Cells to Promote Skeletal Muscle Regeneration.

Stem Cells Int

December 2024

Shanghai Key Laboratory of Craniomaxillofacial Development and Diseases, Shanghai Stomatological Hospital and School of Stomatology, Fudan University, Shanghai, China.

Article Synopsis
  • Dental pulp stem cells (DPSCs) show promise for muscle injury repair, but their ability to differentiate into muscle cells is currently limited.
  • Treating DPSCs with Noggin, which inhibits bone morphogenetic protein (BMP) signals, enhances myogenic differentiation, increases myogenic markers, and generates satellite-like cells, improving muscle regeneration.
  • Implanting Noggin-treated DPSCs in a mouse model of muscle loss resulted in significant reductions in defect size and scar tissue, indicating that BMP/Smad signaling regulation by Noggin effectively promotes muscle repair.
View Article and Find Full Text PDF

Single-nucleus transcriptome profiling provides insights into the pathophysiology of adhesive arachnoiditis.

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 PDF

Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning.

Nat 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 PDF

A tunable human intestinal organoid system achieves controlled balance between self-renewal and differentiation.

Nat 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.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!