Combining Porous Se@SiO₂ Nanocomposites and dECM Enhances the Myogenic Differentiation of Adipose-Derived Stem Cells

Abstract

Background

Volumetric Muscle Loss (VML) denotes the traumatic loss of skeletal muscle, a condition that can result in chronic functional impairment and even disability. While the body can naturally repair injured skeletal muscle within a limited scope, patients experiencing local and severe muscle loss due to VML surpass the compensatory capacity of the muscle itself. Currently, clinical treatments for VML are constrained and demonstrate minimal efficacy. Selenium, a recognized antioxidant, plays a crucial role in regulating cell differentiation, anti-inflammatory responses, and various other physiological functions.

Methods

We engineered a porous Se@SiO₂ nanocomposite (SeNPs) with the purpose of releasing selenium continuously and gradually. This nanocomposite was subsequently combined with a decellularized extracellular matrix (dECM) to explore their collaborative protective and stimulatory effects on the myogenic differentiation of adipose-derived mesenchymal stem cells (ADSCs). The influence of dECM and NPs on the myogenic level, reactive oxygen species (ROS) production, and mitochondrial respiratory chain (MRC) activity of ADSCs was evaluated using Western Blot, ELISA, and Immunofluorescence assay.

Results

Our findings demonstrate that the concurrent application of SeNPs and dECM effectively mitigates the apoptosis and intracellular ROS levels in ADSCs. Furthermore, the combination of dECM with SeNPs significantly upregulated the expression of key myogenic markers, including MYOD, MYOG, Desmin, and myosin heavy chain in ADSCs. Notably, this combination also led to an increase in both the number of mitochondria and the respiratory chain activity in ADSCs.

Conclusion

The concurrent application of SeNPs and dECM effectively diminishes ROS production, boosts mitochondrial function, and stimulates the myogenic differentiation of ADSCs. This study lays the groundwork for future treatments of VML utilizing the combination of SeNPs and dECM.

Graphical Abstract

Keywords:

• porous Se@SiO₂ nanocomposite
• SeNPs
• adipose-derived mesenchymal stem cells
• ADSCs
• decellularized extracellular matrix
• dECM
• myogenic differentiation
• mitochondria

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval for the version to be published; and agree to be accountable for all aspects of the work. Authors Yu-Cheng Zhang and Yu-Xia Yang made equal contributions to this study and should be regarded as co-first authors, the two authors are ranked in no particular order.

Disclosure

The authors confirm the absence of any conflicts of interest in this work.

Additional information

Funding

The study was funded by the National Orthopaedic Sports Medicine and Rehabilitation Clinical Research Center under the project numbered 2021-NCRC-CXJJ-PY-07 and the scientific research project of Jiangsu Provincial Health Commission (M2021042). Furthermore, additional funding was extended through the Wuxi “Double Hundred” Young and Middle-aged Medical and Health Reserve Top-notch Talent Project, Medical and Public Health Technology Innovation and Application Project of Wuxi Science and Technology Bureau (N20202041).