Magnetic nanoparticles stimulate stem cells to regenerate bones

Researchers in bone tissue regeneration believe they have made a significant breakthrough for sufferers of bone trauma, disease or defects such as osteoporosis.

Medical researchers from Keele University and Nottingham University have found that magnetic nanoparticles coated with targeting proteins can stimulate stem cells to regenerate bone. Researchers were also able to deliver the cells directly to the injured area, remotely controlling the nanoparticles to generate mechanical forces and maintain the regeneration process through staged releases of a protein growth stimulant.

Stem Cells Translational Medicine – Remotely Activated Mechanotransduction via Magnetic Nanoparticles Promotes Mineralization Synergistically With Bone Morphogenetic Protein 2: Applications for Injectable Cell Therapy

The current method for repairing bone that can’t heal itself is through a graft taken from the patient. Unfortunately, this can be a painful, invasive procedure, and when the area that needs repair is too large or the patient has a skeletal disorder such as there can sometimes be a lack of healthy bone for grafting.

For this reason, spurring the growth of new bone through injected stem cells is an area of great interest to medical researchers. Much progress has been made, but a major hurdle remains – finding an appropriate means to stimulate the differentiation of the stem cells so they become the quality of bone tissue needed in a quantity large enough to treat patients effectively.

James Henstock, Ph.D. led the Biotechnology and Biological Sciences Research Council (BBSRC)-funded study, alongside Alicia El Haj, Ph.D., and colleagues at Keele University’s Institute for Science and Technology in Medicine, as well as Kevin Shakesheff, Ph.D., from the University of Nottingham’s School of Pharmacy.

James Henstock said: “Injectable therapies for regenerative medicine show great potential as a minimally invasive route for introducing therapeutic stem cells, drug delivery vehicles and biomaterials efficiently to wound sites.”

“In our investigation we coated magnetic nanoparticles with specific targeting proteins then controlled them remotely with an external magnetic field to simulate exercise. We wanted to learn how this might affect the injected stem cells and their ability to restore functional bone.”

The team of researchers conducted their test using two models: chicken foetal femurs and tissue-engineered collagen hydrogels. In both instances the results showed an increase in bone formation and density without causing any mechanical stress to the construct or surrounding tissue.

“This work demonstrates that providing the appropriate mechanical cues in conjunction with controlled release of growth factors to these injectable cell therapies can have a significant impact on improving bone growth. It also could potentially improve tissue engineering approaches for translational medicine” Dr. Henstock said.

Abstract

Bone requires dynamic mechanical stimulation to form and maintain functional tissue, yet mechanical stimuli are often lacking in many therapeutic approaches for bone regeneration. Magnetic nanoparticles provide a method for delivering these stimuli by directly targeting cell-surface mechanosensors and transducing forces from an external magnetic field, resulting in remotely controllable mechanotransduction. In this investigation, functionalized magnetic nanoparticles were attached to either the mechanically gated TREK1 K+ channel or the (integrin) RGD-binding domains of human mesenchymal stem cells. These cells were microinjected into an ex vivo chick fetal femur (embryonic day 11) that was cultured organotypically in vitro as a model for endochondral bone formation. An oscillating 25-mT magnetic field delivering a force of 4 pN per nanoparticle directly against the mechanoreceptor induced mechanotransduction in the injected mesenchymal stem cells. It was found that cells that received mechanical stimuli via the nanoparticles mineralized the epiphyseal injection site more extensively than unlabeled control cells. The nanoparticle-tagged cells were also seeded into collagen hydrogels to evaluate osteogenesis in tissue-engineered constructs: in this case, inducing mechanotransduction by targeting TREK1 resulted in a 2.4-fold increase in mineralization and significant increases in matrix density. In both models, the combination of mechanical stimulation and sustained release of bone morphogenetic protein 2 (BMP2) from polymer microspheres showed a significant additive effect on mineralization, increasing the effectiveness of BMP2 delivery and demonstrating that nanoparticle-mediated mechanotransduction can be used synergistically with pharmacological approaches for orthopedic tissue engineering to maximize bone formation

SOURCE – Keele University, Stem Cells Translational Medicine

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