Al-Sharabi, Niyaz; Mohamed-Ahmed, Samih; Shanbhag, Siddharth; Kampleitner, Carina; Elnour, Rammah; Yamada, Shuntaro; Rana, Neha; Birkeland, Even; Tangl, Stefan; Gruber, Reinhard; Mustafa, Kamal (2024). Osteogenic human MSC-derived extracellular vesicles regulate MSC activity and osteogenic differentiation and promote bone regeneration in a rat calvarial defect model. Stem cell research & therapy, 15(33) BioMed Central 10.1186/s13287-024-03639-x
|
Text
s13287-024-03639-x.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (8MB) | Preview |
BACKGROUND
There is growing evidence that extracellular vesicles (EVs) play a crucial role in the paracrine mechanisms of transplanted human mesenchymal stem cells (hMSCs). Little is known, however, about the influence of microenvironmental stimuli on the osteogenic effects of EVs. This study aimed to investigate the properties and functions of EVs derived from undifferentiated hMSC (Naïve-EVs) and hMSC during the early stage of osteogenesis (Osteo-EVs). A further aim was to assess the osteoinductive potential of Osteo-EVs for bone regeneration in rat calvarial defects.
METHODS
EVs from both groups were isolated using size-exclusion chromatography and characterized by size distribution, morphology, flow cytometry analysis and proteome profiling. The effects of EVs (10 µg/ml) on the proliferation, migration, and osteogenic differentiation of cultured hMSC were evaluated. Osteo-EVs (50 µg) or serum-free medium (SFM, control) were combined with collagen membrane scaffold (MEM) to repair critical-sized calvarial bone defects in male Lewis rats and the efficacy was assessed using µCT, histology and histomorphometry.
RESULTS
Although Osteo- and Naïve-EVs have similar characteristics, proteomic analysis revealed an enrichment of bone-related proteins in Osteo-EVs. Both groups enhance cultured hMSC proliferation and migration, but Osteo-EVs demonstrate greater efficacy in promoting in vitro osteogenic differentiation, as evidenced by increased expression of osteogenesis-related genes, and higher calcium deposition. In rat calvarial defects, MEM with Osteo-EVs led to greater and more consistent bone regeneration than MEM loaded with SFM.
CONCLUSIONS
This study discloses differences in the protein profile and functional effects of EVs obtained from naïve hMSC and hMSC during the early stage of osteogenesis, using different methods. The significant protein profile and cellular function of EVs derived from hMSC during the early stage of osteogenesis were further verified by a calvarial bone defect model, emphasizing the importance of using differentiated MSC to produce EVs for bone therapeutics.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > School of Dental Medicine > Department of Periodontology |
UniBE Contributor: |
Gruber, Reinhard |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1757-6512 |
Publisher: |
BioMed Central |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
07 Feb 2024 09:16 |
Last Modified: |
08 Feb 2024 03:29 |
Publisher DOI: |
10.1186/s13287-024-03639-x |
PubMed ID: |
38321490 |
Uncontrolled Keywords: |
Bone regeneration Extracellular vesicles Mesenchymal stem cells Naïve-EVs Osteo-EVs Rat calvarial defects |
BORIS DOI: |
10.48350/192647 |
URI: |
https://boris.unibe.ch/id/eprint/192647 |
Actions (login required)
 |
Edit item |