Extracellular vesicles from mesenchymal stromal cells for the treatment of inflammatory conditions
Professor Karl-Henrik Grinnemo explains: The drug consists of something similar to small bubbles, called extracellular vesicles, produced by bone marrow mesenchymal stromal cells. These vesicles mediate the function of the mesenchymal stromal cells and act as immunomodulators, protecting cells in a tissue from programmed cell death and stimulating the formation of new blood vessels. Extracellular vesicles are classified as a biological medicine and can be stored for a long time in a standard freezer without changing the properties of the vesicles. This allows for easy distribution to various healthcare facilities around the world where the vesicles can be used as an "off-the-shelf" product - that is, administered directly when the patient needs the treatment. Starting up the concept of extracellular vesicles in Uppsala feels like coming full circle, as Uppsala, through Gunnar Ronquist, has been a pioneer in the research field since the early 1980s.
Grinnemo and his team have extensive experience in treating patients with mesenchymal stromal cells from bone marrow, where two patients with severe Acute Respiratory Distress Syndrome (ARDS) on ECMO (respiratory support; a machine that oxygenates the blood outside the body) were successfully treated already 10 years ago. The immunomodulatory properties of the mesenchymal stromal cells have also been utilized to treat severe SARS-CoV-2 (COVID 19) induced ARDS in a first-in-human study involving seven patients. Since this is a safety study, the primary outcome is focused on the incidence of treatment-related complications and secondary respiratory, systemic and biological outcome measures (EudraCT no 2019-004462-18. ClinicalTrials.gov Identifier: NCT02215811).
The problem with giving mesenchymal stromal cells is that the logistics are very difficult. These cells have to be thawed, quality controlled and their properties are quickly affected during transport to the centers where the cells will be used. The extracellular vesicles, on the other hand, mediate the same properties as the mesenchymal stromal cells, but they are much easier to handle and can serve as an off-the-shelf product that can be given directly on indication. What the vesicles do is influence an overactive inflammatory response by converting immune cells such as pro-inflammatory T cells, neutrophils and macrophages into a more tissue-healing phenotype. Therefore, these extracellular vesicles have great potential to treat a variety of inflammatory conditions, either as a stand-alone treatment or as a potentiation of already established therapies.
Grinnemo and his team are focusing primarily on preventing the severe inflammation that occurs in the heart muscle after treatment of a heart attack with ballooning and stenting, known as PCI. When a previously blocked coronary artery is suddenly opened by PCI, it can lead to severe inflammation and permanent scarring, resulting in heart failure. This project is funded by CAMP-Vinnova. The preclinical studies have been very promising and have shown reduced scarring and preserved cardiac function after treatment with extracellular vesicles from mesenchymal stromal cells. The plan is to start a GMP production of extracellular vesicles at the Rudbeck Laboratory's manufacturing unit and initiate a phase 1 study at Uppsala University Hospital in 2024.