Tandem 8: In-vivo Characterization of Differentiating Muscle Precursor Cells Applying Multi-modal molecular imaging

Short Summary:

Using multi-modal molecular imaging techniques, we characterize MRI properties and the metabolism of differentiating stem cells in-vivo. Thereby, a suitable set of biomarkers will be defined, enabling the non-invasive monitoring of cell therapy approaches in the future.

Scope:

Tissue engineering from adult human stem cells provides a novel therapeutic option for a wide variety of diseases, including muscle regeneration. For monitoring of the successful implementation of replacement tissue, adequate in-vivo imaging techniques for tissue characterization need to be developed. Mature muscle cells exhibit highly specific properties as a potential target for molecular imaging: MRI relaxation and diffusion properties, magnetization transfer, lipid distribution (intramyocellular vs. extramyocellular), adenosine triphosphate (ATP) metabolism of cellular respiration, as well as lactate pyruvate interconversion under anaerobic conditions. Moreover tissue oxygenation seems to potentially inhibit or trigger a certain cell differentiation pathway (Pattappa et al., 2011). The Department of Urology (Delo et al., 2008; Eberli et al., 2009; Eberli et al., 2012) has optimized bio-engineered muscle tissue from different species and aims at the development of a tissue replacement therapy for reconstruction of sphincter muscle. In a collaboration with the DIR (A. Boss), we were able to show that during the differentiation process of adult human muscular progenitor cells in-vivo, the cells adopt MRI relaxation properties reported for mature muscle tissue.

Specific Aims:

Using multi-modal molecular imaging, we will characterize MRI properties and metabolism of differentiating stem cells in-vivo using an established mouse model with correlation to immunohistochemistry. Thereby, a suitable set of biomarkers will be defined, which may serve for monitoring of tissue replacement therapy

Molecular imaging techniques used:

Due to the numerous specific properties of muscular tissue, a large set of molecular imaging techniques need to be evaluated: tissue T1 and T2 relaxation properties (preliminary results established), diffusion MRI, magnetization transfer, 1H spectroscopy for quantification of lipid distribution, blood oxygenation level dependant MRI (BOLD) for assessment of tissue oxygenation, as well as [1-13C]pyruvate and 31P MR spectroscopy (pyruvate and ATP metabolism).

Added value of KFSP for this specific tandem project:

Highly specialized techniques of tissue engineering/cell biology and molecular imaging are brought together in a unique environment.

References