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Secretome analysis of intrathecally applied bone marrow stromal cells in experimental stroke

Objective

"Bone marrow stromal cells (BMSCs) have been shown to be neuroprotective after experimental ischemic stroke when given systemically. By this route of administration, however, over 99% of cells are trapped in lung, spleen and kidneys. This off-target distribution of BMSCs may result in serious ectopic side-effects thereby making their use in humans questionable.

The applicant’s previous work has demonstrated that transplantation of BMSCs to the cerebrospinal fluid compartment (CSFC) reduces post-ischemic brain damage. The cells circulate in the CSFC, attach to ventricular walls and potentially undergo cell-host interactions. Nevertheless, their presence seems sufficient to provide suitable trophic support and promote tissue repair, suggesting a secretory mechanism of action (secretome). Whether the beneficial effect is solely due to the BMSCs secretome in the CSFC or to cross-talk mechanisms between BMSCs and the brain is not clarified. A better understanding of these potential modes of action offers a promising opportunity for future development of ""cell-free"" based therapy.

In this project, we seek to go ahead by studying the CSFC secretome and the observed cell-host interactions of BMSCs after experimental stroke by using state-of-art techniques such as Laser Capture Microdissection and Mass Spectroscopy. The ultimate goal of the project is to determine whether a ""cell-free"" CSFC secretome, which is devoid of any cell-specific side-effects, recapitulates the effects of transplanted BMSCs.

Taken together, this project will analyze the in vivo BMSCs-secretome after cerebral ischemia and will translationally demonstrate the pre-clinical proof-of-concept of a “cell-free” BMSCs therapy for stroke. Due to the high socioeconomic burden of stroke for Europe, novel and effective treatments are urgently needed."

Field of science

  • /medical and health sciences/basic medicine/neurology/stroke
  • /natural sciences/chemical sciences/analytical chemistry/spectroscopy
  • /medical and health sciences/clinical medicine/transplantation
  • /natural sciences/physical sciences/optics/laser physics

Call for proposal

FP7-PEOPLE-2013-IEF
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN
Address
Geschwister Scholl Platz 1
80539 Muenchen
Germany
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 168 794,40
Administrative Contact
Nikolaus Plesnila (Prof.)