To explore the role of MMP2 in regulating the morphology and migration of human mesenchymal stem cells under physiological stress conditions

Sachan, Arya (2021) To explore the role of MMP2 in regulating the morphology and migration of human mesenchymal stem cells under physiological stress conditions. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS Dissertation of Arya Sachan (16MS100)) 16MS049_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (3MB)

Abstract

Mesenchymal stem cells (MSCs) are widely used for treatment of several inflammatory and autoimmune diseases. However, post transplantation, the migration of MSCs to the target site gets compromised reducing the efficacy of treatment. Earlier reports suggest that different stress conditions like febrile temperature, serum starvation and hypoxia, associated with the diseased site, affect the migration of MSCs. However, the underlying mechanism involved in regulating their migration under such stress conditions has been largely unexplored. Here, we are investigating the role of matrix metalloproteinase 2 in regulating the migration of MSCs under stress conditions, as MMP2 is known to play a role in regulating the cell migration. In our study, we had isolated MSCs from Wharton's jelly (WJ) region of freshly collected human umbilical cords. We had used phasecontrast microscopy to observe the changes in the morphology and migration of WJ-MSCs under MMP2/MMP9 inhibition and cells were observed to be flat in appearance under both serum-starved and febrile temperature conditions. Scratch assay performed under MMP2/MMP9 inhibition led to reduction of migration of WJ-MSCs under serum starved condition. Similar decrease had also been observed under febrile temperature. mRNA expression of two ECM molecules MMP1 and VTN which were suspected to have a role in migration of WJ-MSCs revealed that their expression might be regulated by MMP2/MMP9, as observed from MMP2/MMP9 inhibition studies. MMP2/MMP9 was also observed to have a role in proliferation of WJ-MSCs under serum starved condition as its inhibition reduced the cell proliferation rate of WJ-MSCs. Decrease in the expression of cell cycle markers like CCNA2 and E2FA also indicated the reduced cell proliferation rate of WJ-MSCs under MMP2/MMP9 inhibition. Parallely, we had also looked at the migration of WJ-MSCs under another stress condition, hypoxia and observed it to be similar to the control condition where mRNA expression of some ECM molecules known to be involved in migration also showed similar profile.

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