What are MSCs and MSC-EVs?
MSC stands for mesenchymal stromal cells. MSCs are currently being explored as potential therapies for diseases ranging from Alzheimer’s Disease to Acute Kidney Injury to Osteoarthritis. Besides MSCs, extracellular vesicles produced by MSCs (MSC-EVs) are also an attractive therapeutic candidate as these vesicles contain pro-regenerative, immunomodulatory signals that can mediate cellular responses in different disease contexts.
Why are there no approved MSC or MSC-EV therapies?
MSCs and MSC-EVs are regulated by the Food and Drug Administration and therefore undergo premarket evaluation (i.e. clinical trials) prior to licensure. Currently, there are no FDA approved MSC/MSC-EV products. Some of the major challenges facing successful clinical translation of MSC-based therapies are:
We can’t make them the same every time!
- We call this functional heterogeneity i.e. different batches of MSCs and MSC-EVs produced under different conditions and derived from different starting materials (e.g. donors and/or tissues) do not possess the same functional (‘therapeutic’) properties
We don’t know what to measure to ensure they ‘work’
- Related to functional heterogeneity, there are no well-established methods to predict whether a given batch of MSCs or MSC-EVs are ‘good’ or ‘bad’ before giving to a patient.
We don’t know how to show that they will work as intended!
- Need for better ‘potency assays’: Assays of MSC/MSC-EV ‘potency’ (defined by FDA here) are needed to evaluate different batches of MSC/MSC-EVs in a disease-relevant context. A desired potency assay is robust, ensures consistency and enables selection of MSC/MSC-EV batches with desired characteristics for a given application. A potency assay can be considered an ‘aptitude test’ for MSCs or MSC-EVs!
How we make them is not consistent!
- Manufacturing consists of all the materials and steps involved in taking starting material (cells or tissue) and processing it to produce a final drug product (MSCs or MSC-EVs). This can include chemicals like digestion enzymes or cell culture media, as well as materials/equipment like microcarriers, bioreactors, or T-flasks. MSCs respond to diverse microenvironment cues and therefore changes in these cues due to manufacturing can have profound effects on their function.
How does our lab address these problems facing MSC/MSC-EV translation?
Please click on sections of the MSC product manufacturing process to see what we’re working on!
MSC Manufacturing – How does manufacturing impact MSC quality?
MSC-EV Manufacturing – How does manufacturing impact MSC-EV quality?
Quality Control – How do we predict and assess quality?
Mechanism of Action – How do they work?!