Tailoring therapies to ensure personalized treatments for better outcomes
Over the past decade, we have begun to appreciate that the same disease affects different people in different ways. Furthermore, every patient is unique in the way they process, and hence respond to, drugs. Together, this can result in a drug having a varied response profile in different patients, which makes treating diseases very challenging. One exciting avenue emerging is the integration of new cell therapies into personalized treatment plans specific for individual patients. The main advantage of cells, given they are living entities, is their ability to adapt their response-profile to a particular disease. However, this makes cells difficult to standardize for reproducible effects.
One promising cell therapy that our lab focuses on are mesenchymal stem cells (MSCs) given their ability to orchestrate tissue regeneration in almost all organ systems. Furthermore, these cells produce and secrete extra-cellular vesicles (MSC-EVs) which can be used as a cell-free therapy given their cargo of signaling molecules, proteins, mRNAs, miRNAs, lipids, DNA and/or functional mitochondria.
To ensure the successful clinical translation of MSC therapies (i.e. MSCs and MSC-EVs), it is important to understand their intrinsic molecular and regenerative signatures. Hence, our lab has been extensively profiling these therapies to ensure we can match the correct MSC therapy to a specific disease process (i.e. Precision Therapy). In addition, we have been optimizing the precision delivery of these therapies as well as exploring technologies that can modulate both the therapy and the target tissue microenvironment. In the latter case, we soundwaves are able to create a “molecular signal” that can help MSC therapies repair injured tissues.
Microenvironment Modulation. The tissue microenvironment consists of a dynamic population of cellular and non-cellular components which form a multifaceted network. Our research aims to use technologies to manipulate the microenvironment (i.e. using soundwaves in the form of therapeutic ultrasound) to create an unprecedented opportunity to facilitate tissue regeneration, stem cell homing and permeation, and immune cell modulation. When coupled to the precision delivery, we hope to enhance the therapeutic potential of any therapy to ensure maximal benefit for patients. In the setting of cancer, soundwaves can also manipulate the stroma around cancer cells, as well as alter tumor blood vessel integrity, thereby helping therapies to cross the vasculature and effectively access tumor cells.
Mesenchymal Stem Cell Therapies. MSCs (cell therapy) and MSC-EVs (cell-free therapy) offer promising disease agnostic regenerative therapies given their pro-angiogenic, anti-inflammatory, immunomodulatory, anti-fibrotic and bioenergetic properties. Our research focuses on characterizing the phenotype of these therapies, at the genomic, proteomic, and lipidomic levels, as well as enhancing their regenerative phenotype using genetic modification and novel priming technologies.
Therapy Optimization. While MSCs have potent regenerative effects, their effects can be further augmented through genetic modification or by “priming” the parent cell. Our research focuses on producing source-specific MSCs which overexpress specific proteins as well as using unique non-invasive techniques to augment the bioenergetic profile of MSC therapies, which can be seen as the ability of the parent MSC producing tunneling nanotubes (TNTs) or MSC-EVs containing cargo with high mitochondria and miRNA content.