Mesenchymal stem cells are culture-derived mesodermal progenitors isolatable from all vascularized tissues. In spite of multiple fundamental, pre-clinical and clinical studies, the native identity and role in tissue repair of MSCs have long remained elusive, with MSC selection in vitro from total cell suspensions essentially unchanged as a mere primary culture for half a century. Recent investigations have helped understand the tissue origin of these progenitor cells, and uncover alternative effects of MSCs on tissue healing via growth factor secretion and interaction with the immune system. In this review, we describe current trends in MSC biology and discuss how these may improve the use of these therapeutic cells in tissue engineering and regenerative medicine.

Abstract18F-sodium fluoride (18F-NaF) is a positron emission tomography (PET) radiotracer widely used in skeletal imaging and has also been proposed as a biomarker of active calcification in atherosclerosis. Like most PET radiotracers, 18F-NaF is typically administered intravenously. However in small animal research intravenous administrations can be challenging, because partial paravenous injection is common due to the small calibre of the superficial tail veins and repeat administrations via tail veins can lead to tissue injury therefore limiting the total number of longitudinal scanning points. In this paper, the feasibility of using intra-peritoneal route of injection of 8F-NaF to study calcification in mice was studied by looking at the kinetic and uptake profiles of normal soft tissues and bones versus intra-vascular injections. Dynamic PET was performed for 60 min on nineteen isoflurane-anesthetized male Swiss mice after femoral artery (n = 7), femoral vein (n = 6) or intraperitoneal (n = 6) injection of 8F-NaF. PET data were reconstructed and the standardised uptake value (SUV) and standardised uptake value ratio (SUVr) were estimated from the last three frames between 45- and 60-min and 8F-NaF uptake constant (Ki) was derived by Patlak graphical analysis. In soft tissue, the 18F-NaF perfusion phase changes depending on the type on injection route, whereas the uptake phase is similar regardless of the administration route. In bone tissue SUV, SUVr and Ki measures were not significantly different between the three administration routes. Comparison between PET and CT measures showed that bones that had the highest CT density displayed the lowest PET activity and conversely, bones where CT units were low had high 8F-NaF uptake. Intraperitoneal injection is a valid and practical alternative to the intra-vascular injections in small-animal 18F-NaF PET imaging providing equivalent pharmacokinetic data. CT outcome measures report on sites of stablished calcification whereas PET measures sites of higher complexity and active calcification.