Stem cell‐mediated accelerated bone healing observed with in vivo molecular and small animal imaging technologies in a model of skeletal injury

Abstract

Adult stem cells are promising therapeutic reagents for skeletal regeneration. We hope to validate by molecular imaging technologies the in vivo life cycle of adipose-derived multipotent cells (ADMCs) in an animal model of skeletal injury. Primary ADMCs were lentivirally transfected with a fusion reporter gene and injected intravenously into mice with bone injury or sham operation. Bioluminescence imaging (BLI), [18F]FHBG (9-(fluoro-hydroxy-methyl-butyl-guanine)-micro-PET, [18F]Fluoride ion micro-PET and micro-CT were performed to monitor stem cells and their effect. Bioluminescence microscopy and immunohistochemistry were done for histological confirmation. BLI showed ADMC’s traffic from the lungs then to the injury site. BLI microscopy and immunohistochemistry confirmed the ADMCs in the bone defect. Micro-CT measurements showed increased bone healing in the cell-injected group compared to the noninjected group at postoperative day 7 (p <0.05). Systemically administered ADMC’s traffic to the site of skeletal injury and facilitate bone healing, as demonstrated by molecular and small animal imaging. Molecular imaging technologies can validate the usage of adult adipose tissue-derived multipotent cells to promote fracture healing. Imaging can in the future help establish therapeutic strategies including dosage and administration route.

In Vivo Mesenchymal Stem Cell Tracking with PET Using the Dopamine Type 2 Receptor and 18F-Fallypride

“…PET imaging of hMSCs expressing herpes simplex virus type 1 thymidine kinase (HSV1-Tk) implanted subcutaneously was recently described in the literature (27). In contrast, monitoring of HSV1-TK-expressing hMSCs in a 0.5-mm-sized bone defect could not be established (28).…”

Nanoparticles and their potential for application in bone

“…The promising fields for MSC application range from promoting bone regeneration 19,20 to improving fracture healing. [21][22][23][24] To monitor these processes, MSCs have been labeled with diverse nanoparticles, such as quantum dots, which are small semiconductor nanocrystals, 25,26 fluorescence-labeled mesoporous silica nanoparticles, 27 gold nanoparticles, 28 or superparamagnetic iron oxide (SPIO) nanoparticles. [29][30][31] Several types of SPIO nanoparticles have already been clinically approved for use as contrast agents in MRI, eg, of bowel or liver.…”

Advances in multimodality molecular imaging of bone structure and function

“…This indi- Multimodality molecular imaging of bone FM Lambers et al cated that MSCs promoted healing, which could only be verified through a multimodality approach. 74 Bone morphogenic protein-2 (BMP2) is an osteoinductive protein that can induce bone formation in vivo . Therefore, MSCs overexpressing BMP2 (MSCs -BMP2) could enhance bone healing.…”