Research Projects

Regenerative medicine-based therapies have brought hope for the treatment of diseases which only had supportive therapies. Mesenchymal Stem Cells (MSCs) have been recognized widely for their regenerative potential. They have gained popularity in regenerative medicine due to their ability to differentiate, immunomodulatory capabilities, and secretion of paracrine mediators such as extracellular vesicles (EVs). MSCs exist in vivo in a hypoxic niche consisting 1-7% oxygen. Studies have reported that hypoxia exposure to MSCs in vitro as well helps in enhancing their therapeutic functionalities, especially via enhancing the release of EVs. EVs are tiny membrane bound structures secreted regularly by cells for intercellular communication. These include a heterogenous population of vesicles including majorly exosomes, microvesicles, apoptotic bodies. These EVs carry miRNA and mRNA, proteins, and other cargo that help heal damaged or diseased tissues and organs. Studies have reported that hypoxia exposure to MSCs enhances their therapeutic function, especially via augmenting the release & content of their extracellular vesicles (EVs). These EVs have also been implicated in protecting against a wide range of disorders, reduce oxidative stress, and exhibit immunomodulatory activities equivalent to their parent cells. Owing to these advantages, currently the focus of regenerative medicine has shifted to cell free therapy, and EVs serve as the perfect candidate for that. These tiny membranes bound vesicles can also serve as a perfect platform for drug loading and delivery via bioengineering strategies in order to develop the next generation of nano-pharmaceuticals in regenerative medicine. Their double membrane bound structures make them equivalent to liposome based nano formulations, while having the advantage of being naturally derived. However, these EVs package the contents of the cell based upon the physiological state of the cell, and there is yet no insights into the exact mechanism via which the EVs package their cargo which poses a problem of non-specific effects. Moreover, these EVs sometimes be eliminated from the body while in circulation without ever homing towards the target organ due to lack of specificity. Therefore, in order to overcome these shortcomings, this project aims to take lieu of multivariate approaches for bioengineering of these EVs via surface modification and cargo modification on one platform in order to get them ready for translational applications & drug formulation. The bioengineered EVs so developed will be validated using 2 different routes of administration, including topical application, and intravenous administration, in order to evaluate their homing capability and target specificity (via surface modification) & functional specificity (cargo modification) in both in vitro and in vivo models.