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Stem cell derived exosome therapy for clinical management of lung
damage in critically-ill corona viral pneumonia patients
A recent study by Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), hypothesises to explore the Mesenchymal Stem Cell (MSC)-derived extracellular vesicles, otherwise called exosomes, as a potential regenerative regime for lung regeneration in ARDS mice models.
They hypothesise that the immuno-modulatory and the reparative properties of MSC-derived exosomal fractions will aid in controlling the cytokine storm and lung tissue regeneration in critically ill COVID-19 patients. In this project, they first isolate MSCs from Wharton’s jelly of umbilical cord (WJ-MSCs) from healthy donors after taking informed consent. Subsequently, sub-confluent WJ-MSCs in culture will be grown in serum-free medium, the used medium will be collected and subjected to ultra-centrifugation to obtain exosomal fraction. Surface marker (CD63, CD81 and TSG101), total particle number, size and total protein content analysis of resultant exosome fraction will be characterised as per reported protocols. To assess the regenerative potential of this exosomal fraction, they will develop an acute lung damage model in SD rats (n=6/group) and treat the animals with exosome based inhalation formulation. One group provided with WJ-MSCs and another group without any treatment would be considered for comparison. The extent of lung vascular remodeling, alveolarisation and pulmonary hypertension will be assessed. Further, one of the challenges in MSC-based therapies is the limited number of availability at source and requirement of large number of cells for clinical application. In this project, they will also work on development of ex-vivo expansion system using novel cell carriers. Overall, the project aims to offer WJ-MSC-exosomal-based therapy for lung regeneration in critically-ill patients suffering from pneumonia caused by SARS-CoV-2 in particular and any other lung damage with similar pathophysiology.
Contact info:
naresh.kasoju@gmail.com
Artificial intelligence in COVID-19 drug repurposing
Drug repurposing or repositioning is a technique whereby existing drugs are used to treat emerging and challenging diseases, including COVID-19. Drug repurposing has become a promising approach because of the opportunity for reduced development timelines and overall costs. In the big data era, artificial intelligence (AI) and network medicine offer cutting-edge application of information science to defining disease, medicine, therapeutics, and identifying targets with the least error.
They want to develop a model harnessing AI and ML approaches that can be able to select and prioritise drugs according to descriptor properties in a lesser time. The drug target selection involves two way strategies: one to identify targets in virus, and other to identify proteins or enzymes in human that are required for virus attachment and entry inside the host cell. Virtual screening and docking approaches will be preferred to find correct orientation of ligand at the active site. Nowadays molecular dynamics simulations allow the observation of unsupervised ligand−target binding, assessing how these approaches help in optimising target affinity and drug residence time toward improved drug efficacy. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate estimate of the thermodynamics and kinetics associated with drug-target recognition and binding. So, they want to monitor and analyse the dynamics of drug-receptor interaction in real time using molecular
VOL. IV ISSUE 10
VIGYAN PRASAR 16
COVID-19 SCIENCE & TECHNOLOGY EFFORTS IN INDIA