Biological signature and efficacy of mesenchymal stem cell-based therapies

Vast efforts have been put towards developing mesenchymal stem cell (MSC) therapy for various disorders.

However, obstacles exist due to undefined mechanisms of action and difficulties in large scale manufacture of uniform MSC.We have developed the highly bone-forming fetal MSC for clinical use, with initial patient data showing promising results for treatment of brittle bone disease (Osteogenesis Imperfecta).

The approved European trial BOOSTB4 beginning in March 2020 will provide unique insight into MSC therapy for inherited disorders.

The proposed project does not directly include the trial, but is strongly linked to it and will utilize its biological samples.Following intravenous infusion, fetal MSC migrate to the bones, partially engraft and form bone cells.

Their clinical effect (reduction of fractures and growth in height) is transient, suggesting that they also act through triggering the body’s own regenerative machinery via extracellular vesicles (EVs), which are vital in intercellular communication.Our purpose is to enhance the manufacturing and predict therapeutic outcome to improve the clinical efficacy of MSC-therapies.

We will examine the biological signature of well characterized fetal MSC and investigate mechanisms of action using mass spectrometry, flow cytometry, sequencing and cell culture methods.Successfully treating children will result in greater health benefits, transforming the future care of the pediatric population where few therapies are developed.