Bone Targeted Delivery of Mitochondria Wrapped in Artificial Cell Membranes
The first companies working towards mitochondrial transplantation therapies to alleviate age-related mitochondrial dysfunction are primarily focused on logistics, the work needed to establish high quality manufacturing processes capable of producing the very large numbers of mitochondria needed for human subjects. Meanwhile, the research community is engaged in finding novel ways to engineer mitochondria and methods of delivery to improve this approach to therapy. One example is reported here, involving the encapsulation of mitochondria in artificial cell membranes and guidance of their trajectory in the body via magnetic fields.
A major clinical obstacle in the aging population is the significantly reduced regenerative capacity of bone, often resulting in delayed fracture healing or nonunion fractures. Mitochondria, as the central regulators of cellular energy metabolism, are essential for determining cell fate and supporting tissue regeneration. However, age-associated mitochondrial dysfunction critically impairs these processes. While transplanting healthy mitochondria is a promising therapeutic strategy, its efficacy is severely limited by poor targeting efficiency and inherent fragility of mitochondria in circulation.
We constructed artificial cell microspheres (Fmito@ACs) containing mitochondria of fetal mouse mesenchymal stem cells and conducted systematic characterization of them. In vitro experiments evaluated the effects of Fmito@ACs on the functions of primary osteoblasts, and its role in delaying cellular senescence was analyzed through β-galactosidase staining and immunofluorescence analysis of senescence markers (P21 and γH2A.X). Its ability to restore mitochondrial function was assessed by measuring reactive oxygen species, morphology, and energy metabolism. In animal experiments, labeled Fmito@ACs were tracked and their targeted accumulation at fracture sites guided by an external magnetic field was verified.
Fmito@ACs were successfully constructed and characterized, indicating a protective effect on mitochondria. The system ameliorated senescence in aged bone marrow mesenchymal stem cells, promoting osteogenesis by enhancing mitochondrial fusion and aerobic glycolysis. In an aged fracture model, Fmito@ACs showed targeted accumulation and biosafety, significantly improving healing.
INTERESTING, especially in the context of your other highlighted update showcasing the importance of mitochondria in Alzheimer's!
Fmito@ACs - are they BBB-permeable? (Has their CNS penetration been assessed)?