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Mahsa Khayatkhoei, MD, MBA

Job Title

research fellow

Academic Rank

Fellow or Postdoc

Department

Neurology

Authors

Mahsa Khayat-Khoei, Susanna B. Mierau, Howard L. Weiner

Principal Investigator

Mahsa Khayat-Khoei

Categories

Tags

In vitro model for investigating the effect of multiple sclerosis monocytes on cellular-scale cortical network function.

Scientific Abstract

Introduction: Progressive multiple sclerosis (MS) results from local central nervous system (CNS) inflammation driven by CNS-resident cells following the infiltration of cells such as monocytes from the periphery. Yet little is known about the role of monocytes in different stages of MS.

Methods: We compared network activity in healthy human cortical neurons and astrocytes with and without the presence of MS-derived or healthy monocytes using microelectrode array (MEA) system. Recordings of cortical neurons were performed before adding monocytes and following the addition of monocytes to culture for 6.5 weeks, and data was analyzed.

Results: The addition of Progressive MS monocytes in comparison to healthy control monocytes led to temporary disruption of neuronal function without causing toxicity to the culture and we were able to record network activity until days-in-vitro 45. We had a 40 percent increase in action potential after feeding, suggesting robust activity. Next, we will test different concentrations of monocytes and compare cell-autonomous and non-cell-autonomous effects on the cortical networks.

Conclusion: Our study aims to establish an in vitro humanized platform for testing the effect of monocytes, or other immune cells, on cortical function. This model may provide both mechanistic insights and be utilized for screening potential therapeutics.

Lay Abstract

Introduction: Progressive multiple sclerosis (MS) results from local central nervous system (CNS) inflammation driven by immune cells that are inside the CNS. A group of immune cells called monocytes might contribute to this but their role is not yet well investigated in different stages of MS.

Methods: We compared network activity in healthy human neurons (brain cells) that were made from stem cells, with and without the presence of MS or healthy monocytes. We used specially designed plates for recording the brain cell function called synaptic activity for 6.5 weeks and we analyzed the data.

Results: Adding the progressive MS monocytes temporarily disturbed the brain cell function but was not toxic to the neurons and we were able to record the network activity until days-in-vitro 45. We had a 40 percent increase in action potential after each feeding which suggested a good cell culture. Next, we will test different concentrations of monocytes and compare their effect on neuronal cells.

Conclusion: Our study aims to establish a human-based model for testing the effect of monocytes, or other immune cells, on human brain cell function. This model may provide more information about MS disease and help in screening for treatments.

Clinical Implications

We are creating a unique humanized platform for testing the effect of immune cells on cortical function. This can help in better understanding the pathology of progressive MS and designing targeted therapies for this disease which we currently don’t have.