ORIGINAL RESEARCH article
Front. Bioeng. Biotechnol.
Sec. Tissue Engineering and Regenerative Medicine
Volume 13 - 2025 | doi: 10.3389/fbioe.2025.1655579
This article is part of the Research TopicTranslation of Mesenchymal Stem Cells in vivo: Evidence from preclinical and clinical testing.View all 10 articles
Pulsed electromagnetic fields preconditioned extracellular vesicles derived from mesenchymal stromal cells prevents necroptosis of osteoblasts in osteonecrosis of the femoral head rats
Provisionally accepted
- West China Hospital, Sichuan University, Chengdu, China
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Background: Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic disease in which steroids may induce bone cell necroptosis. Extracellular vesicles derived from bone marrow mesenchymal stromal cells (BMSC-EVs) are recognized as novel therapies to improve ONFH. Pulsed electromagnetic fields (PEMFs) increase the paracrine activity of BMSCs. Nonetheless, the effect and mechanism of PEMFs preconditioned BMSC-EVs (BMSC-EVsPEMFs) for treating ONFH are unclear. Methods: The BMSC-EVsPEMFs with different magnetic amplitudes were incubated with dexamethasone-induced MC3T3-E1 cells and the osteogenic differentiation and necroptosis were observed. Furthermore, RNA sequencing of MC3T3-E1 cells incubated with incubated with PEMFs of a specific amplitude or without PEMFs was conducted to identify potential mechanisms involved. Reverse transcription‒quantitative polymerase chain reaction (RT-qPCR), immunofluorescence and western blotting were performed to detect necroptosis-related pathways. SD rats receiving steroid injections were randomly assigned to receive PBS, BMSC-EVs or BMSC-EVsPEMFs therapy. Micro-CT scan, histological, and immunohistochemical analyses were used to evaluate the therapeutic effects on bone formation and necroptosis of the femoral head in ONFH animals. Results: The characteristics of the BMSC-EVsPEMFs were similar to those of the BMSC-EVs. In vitro, co-culture of osteoblasts and PEMFs with 3 millitesla (mT) amplitude preconditioned BMSC-EVs (BMSC-EVsPEMFs (3 mT) promoted osteogenic differentiation and inhibited cell death. The results of RNA sequencing revealed that the expression of Ripk3 was significantly lower in the BMSC-EVsPEMFs (3 mT) group than in the BMSC-EVs group. RT-qPCR, immunofluorescence and western blotting revealed that the expression of necroptosis-related molecules (RIPK1, RIPK3, and MLKL) was suppressed in BMSC-EVsPEMFs (3 mT) group (p<0.05). In vivo, the BMSC-EVsPEMFs (3 mT) group presented better bone morphology of the femoral head via micro-CT, with a lower protein expression of MLKL and a higher expression of RUNX2 (p<0.05) at 2 weeks, while lower expressions of RIPK1 and RIPK3, and higher levels of RUNX2 and OCN (p<0.05) at the femoral head at 6 weeks after injection than did the BMSCs-EVs group. Conclusion: PEMFs with 3 millitesla amplitude preconditioned BMSC-EVs could promote bone formation by inhibiting osteoblasts necroptosis via Ripk1–Ripk3–Mlkl signaling in ONFH.
Keywords: Osteonecrosis of the femoral head, extracellular vesicles, Bone marrow mesenchymalstromal cells, Pulsed electromagnetic fields, necroptosis
Received: 28 Jun 2025; Accepted: 18 Sep 2025.
Copyright: © 2025 Xiang, Zhang, Wang, He and He. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Chengqi He, hxkfhcq2015@126.com
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