Project

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Non-invasive monitoring of muscle precursor cell differentiation in vivo by magnetic resonance imaging

English title Non-invasive monitoring of muscle precursor cell differentiation in vivo by magnetic resonance imaging
Applicant Boss Andreas
Number 162533
Funding scheme Project funding
Research institution Institut für Diagnostische Radiologie Departement Medizinische Radiologie Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Biomedical Engineering
Start/End 01.01.2016 - 30.06.2018
Approved amount 277'912.00
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Keywords (2)

stem cells; magnet resonance imaging

Lay Summary (German)

Lead
Stressbedingte Harninkontinenz betrifft ca. 20% der Frauenen, wobei die Quote bei höherem Alter auf bis zu 50% ansteigt. Die Inkontinenz verursacht eine deutliche Verminderung der Lebensqualität und hohe Behandlungskosten. Alle bisherigen Behandlungemöglichkeiten - Training, Medikamente, chirurgische Eingriffe - weisen eine eher enttäuschende Erfolgsquote auf. Die Stammzelltherapie kann hier entscheidende Verbesserungen erbringen. Dieses Projekt soll hierzu einen Beitrag leisten.
Lay summary
Die Therapie mit patienteneigenen Zellen stellt eine vielversprechende Alternative für die Behandlung der Stressinkontinenz dar. Aufgrund ihrer Fähigkeit, Muskelfasern zu bilden, bieten sich Muskelvorläuferzellen (MPCs) für die Reparatur von geschädigtem Muskelgewebe als Quelle für eine autologe Stammzelltherapie an.  Die richtige Struktur und Zusammensetzung des regenerierten Muskelgewebes ist ausschlaggebend für den Erfolg der Zelltherapie. Die derzeitigen Möglichkeiten zur Beurteilung der Gewebequalität und des Regenerationserfolgs sind allerdings stark eingeschränkt, sie umfassen Inkontinenz-Tagebücher oder Umfragen zur Lebensqualität. In dem hier vorliegenden Projekt, sollen Methoden der Magnetresonanztomographie entwickelt und erprobt werden, welche eine nicht-invasive objektive Beurteilung einer Stammzelltherapie im lebenden Organismus erlauben.
Direct link to Lay Summary Last update: 26.10.2015

Responsible applicant and co-applicants

Employees

Publications

Publication
Separation of collagen-bound and porous bone-water longitudinal relaxation in mice using a segmented inversion recovery zero-echo-time sequenceCBW and PW T1 Times Using IR-ZTE
Marcon Magda, Keller Daniel, Wurnig Moritz C., Weiger Markus, Kenkel David, Eberhardt Christian, Eberli Daniel, Boss Andreas (2017), Separation of collagen-bound and porous bone-water longitudinal relaxation in mice using a segmented inversion recovery zero-echo-time sequenceCBW and PW T1 Times Using IR-ZTE, in Magnetic Resonance in Medicine, 77(5), 1909-1915.
Magnetization transfer imaging of cortical bone in vivo using a zero echo time sequence in mice at 4.7 T: a feasibility study
Marcon Magda, Weiger Markus, Keller Daniel, Wurnig Moritz C., Eberhardt Christian, Eberli Daniel, Boss Andreas (2016), Magnetization transfer imaging of cortical bone in vivo using a zero echo time sequence in mice at 4.7 T: a feasibility study, in Magnetic Resonance Materials in Physics, Biology and Medicine, 29(6), 853-862.
Separation of collagen-bound and porous bone water transverse relaxation in mice: proposal of a multi-step approachCortical bone water signal separations in mice using UTE sequences
Marcon Magda, Keller Daniel, Wurnig Moritz C., Eberhardt Christian, Weiger Markus, Eberli Daniel, Boss Andreas (2016), Separation of collagen-bound and porous bone water transverse relaxation in mice: proposal of a multi-step approachCortical bone water signal separations in mice using UTE sequences, in NMR in Biomedicine, 29(7), 866-872.

Abstract

Background Urinary incontinence compromises a patient’s quality of life and inflicts tremendous health care costs. Up-to-date treatment options relying on synthetic materials have currently been heavily criticized due to severe complications and limited success, while advances in cell therapy approaches to treat urinary incontinence show promising results towards correcting the underlying etiology. Evaluating the success of such treatments in vivo is difficult. Mature muscle and other organs exhibit a highly specific pattern of tissue properties in magnetic resonance imaging (MRI) and spectroscopy (MRS). Changes in MR relaxation properties have recently been found to allow for monitoring of myogenic differentiation of adult stem cells in vivo. The quality of the regenerated tissue is of crucial importance for its proper function and thus, reliable and non-invasive markers reflecting the cellular composition and the maturation state of the developing tissue are of great importance for the clinical applicability of cell therapy approaches.Working hypothesis (a) advanced tools of MRI can be used for non-invasive characterization of muscle precursor cell (MPCs) differentiation to mature tissue.(b) MRI is a suitable tool for monitoring stem cell supported muscle regeneration.Specific aims for this research project (a, I) to apply 1H magnetic-resonance spectroscopy (MRS) for investigation of the development of the muscle specific fat metabolism during differentiation of MPCs. (a, II) to apply 31P MRS for the characterization of the developing muscle specific metabolism of adenosine triphosphate (ATP)/ adenosine diphosphate ADP versus creatinine phosphate (CP).(b, I) to apply Diffusion Tensor Imaging (DTI) for the monitoring of stem cell supported muscle fiber regeneration in an in vivo muscle crush model.(b, II) to apply Magnetization Transfer (MT) measurements for measurement of muscle fiber regeneration in an in vivo muscle crush model.Experimental design and methods(a, I) and (a, II) n=12 nude mice will be subcutaneously (sc) injected with 3×107 human MPCs derived from human rectus abdominis muscle. The mice will undergo subsequent spectroscopic measurements at time points 1d, 3d, 7d, 14d, and 21d after injection in a small animal MR scanner using a 1H standard coil and a dedicated 31P coil.(b, I) and (b, II) In two groups, n=12 mice will undergo a standardized muscle crush treatment of the quadriceps femoris muscle with subsequent injection of 3×107 human MPCs (third group: sham group with no treatment). During muscle regeneration, mice will undergo MRI examinations at time points 1d, 3d, 7d, 14d, and 21d applying relaxation measurements of T1, and T2 times, and MT measurements with variation of off-resonance frequencies allowing to compute true MT, and DTI measurements providing fractional anisotropy (FA) and fiber tracking.Expected value of the proposed projectThe first subproject (a) will further enhance our knowledge on the development of muscle specific traits in MRI during differentiation from stem cells towards mature muscle tissue, whereas subproject (b) focuses on a translation of our experiences from MRI characterization of stem cell differentiation towards a clinical application for treatment of muscle regeneration. Both approaches will provide key contributions towards the clinical applicability of stem cell supported muscle therapy and could also be translated to the treatment monitoring of other myogenic disorders.
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