In vivo bioluminescence imaging of transplanted bone marrow mesenchymal stromal cells using a magnetic delivery system in a rat fracture model

Abstract

For the treatment of ununited fractures, we developed a system of delivering magnetic labelled mesenchymal stromal cells (MSCs) using an extracorporeal magnetic device. In this study, we transplanted ferucarbotran-labelled and luciferase-positive bone marrow-derived MSCs into a non-healing femoral fracture rat model in the presence of a magnetic field. The biological fate of the transplanted MSCs was observed using luciferase-based bioluminescence imaging and we found that the number of MSC derived photons increased from day one to day three and thereafter decreased over time. The magnetic cell delivery system induced the accumulation of photons at the fracture site, while also retaining higher photon intensity from day three to week four. Furthermore, radiological and histological findings suggested improved callus formation and endochondral ossification. We therefore believe that this delivery system may be a promising option for bone regeneration.

Mesenchymal Stem Cell-Derived Exosomes Promote Fracture Healing in a Mouse Model

“…A thin saw cut at a depth of 3 mm was applied midshaft after minimal lateral exposure to weaken the bone and to avoid complex fractures. The right femur of each animal was fractured by a three-point bending technique [3,37], after which the muscular fasciae and skin were closed.…”

“…Radiographic imaging was performed at 0, 1, 2, 4, and 6 weeks after fracture. Bone union was defined as the presence of a bridging callus on two cortices [3].…”

“…Transplantation of stem cells, such as bonemarrow-derived mesenchymal stem cells (MSCs), promotes tissue regeneration, including fracture healing [3][4][5]. Many studies indicate that transplanted MSCs contribute to tissue regeneration by mechanisms other than differentiation and direct tissue integration [6][7][8][9].…”

Emerging translational research on magnetic nanoparticles for regenerative medicine

“…168 With the confirmation of co-injected. 111 In-labeled cells by scintigraphic imaging (which provided quantitative information), MRI was able to detect as few as 1.5 Â 10 5 cells in vivo. Most importantly, the detailed anatomical localization of migrated cells that was obtained from MRI could identify true-positive lymph nodes separately, which were missed by scintigraphy because they were located in the same vertical plane as individual lymph nodes.…”

Recent insights on the endogenous bone repair mechanisms and therapeutic applications

“…Although improved healing was observed in the MSC -LIPUS group, the mechanism of action remains to be proven. Kodama et al 24 tracked Fe-labeled MSC after transplantation at the fracture site in rats. MSC enhanced bone regeneration but whether they differentiated into osteoblasts is not clear.…”