Project: MRI Navigated Enhancement of Mesenchymal Stem Cell (MSC) Homing Toward Stroke Lesion – Evaluating an Impact on Animal Recovery with Behavioral Testing and Imaging

Stroke is a major reason of death and the leading cause for permanent disability in industrialized nations, thus putting a significant economical burden on our society. Despite limited treatment option in the very first few hours, there is no effective treatment available to counter the disease and to help survivors to return to pre-morbid societal roles and productivity. Recent progress in the field of stem cell research offers a promising option for enhanced stroke treatment. Positive effects of mesenchymal stem cell (MSC) transplantation were seen in animal models. However, pilot clinical trials did not result in striking functional improvement in patients. This inconsistency could be related to several factors including MSC dose, which, after adjustment to brain weight, was up to an order of magnitude less compared to rodent experiments. The so far low efficiency of MSC therapy in a clinical setting could be increased by facilitating MSC homing towards the brain lesion. Our project aims to develop such an approach, to investigate its feasibility, safety and efficacy in relevant cell culture and animal models and to collect all needed information for safe translation into a clinical testing in case of success. In a first phase, MSC will be engineered to overexpress a certain protein, VLA-4, which enhances cell homing to the lesioned brain. This is expected to cause for higher local (effective) MSC doses to enhance the therapeutic efficacy. The efficacy of the concept will be confirmed in cell culture models. In a second phase, MSC will be labeled with iron particles and tracked by means of magnetic resonance imaging (MRI) in animals. This reveals data on the distribution of the MSC in the brain at high resolution and confirms safety of the approach. Repeated measuring will reduce the number of animals needed and give longitudinal information about MSC biodistribution and protocol safety. Behavioral tests will be used to reveal efficacy of the approach in rodent models of stroke. In a third phase, the approach will be verified in a close-to-practice large animal model offering anatomical conditions being comparable to humans. In case of success, the modified MSC would be ready to be produced for early patient studies. Thus, cells may become an on-target treatment approach for stroke with the perspective for licensing by consortium partners and/or to start-up a spin-off company to attract investors in order to fund pilot clinical trials.

Acronym	MEMS-IRBI
Duration	01/03/2012 - 28/02/2015
Network	NEURON
Call	NEURON-2011 Cerebrovascular Diseases

Project partner

Number	Name	Role	Country
1	Mossakowski Medical Research Centre	Coordinator	Poland
2	University of Leipzig	Partner	Germany
3	University of Eastern Finland	Partner	Finland