Screening of multiple sclerosis using human tissue chip model with vasicine

A. Balasundaram, D. David. Pharmacology, Sri Ramachandra Medical College & Research Institute, Chennai, INDIA.

Introduction: Pharmacologists and researchers have been inspecting for novel drug screening methods. Tissue chip [1] ensures maximum replication of entire body physiology over isolated culture or co-cultures. This study explored creating Multiple Sclerosis (MS) using human tissue chip platform and assessed ability of Vasicine a quinazoline alkaloid [2] derived from Justicia Adhatoda plant in reversing inflammatory pathology of Multiple Sclerosis.

Method: Tissue Chip with a 3D scaffold matric for four types of tissues were used. Human Stem Cells were differentiated using respective growth factors into Neuronal Cells, Cardiomyocytes, Skeletal Muscle Cells and Hepatocytes. Along with these White blood cells were also cultured. The entire system was maintained in a modified culture media with 5% CO2, 37 degree Celsius and circulated with media cycles to prevent metabolite toxin accumulation. Lipopolysaccharides were used for induction of targeted neuronal inflammation. Post induction, the neuronal cells were isolated, cytopathology was performed to confirm MS induction. Expression of MS biomarkers were confirmed by RT- PCR. A total of 9 Biomarkers including Nogo-A, a diagnostic biomarker, HLA-DRB1 1501, CXCL 12, Fetuin-A overexpressed in demyelinating lesions also correlated with progression and recovery of MS. To identify if Vasicine had MS protective or recovery effect, it was added to the tissue chip.

Results: Vasicine treated Multiple sclerosis induced neuronal cells reverted 80% to normal cell morphology with 20% of remnant inflammation (table 1). The other cell types displayed normal morphology prior and after Vasicine treatment .The therapeutic effect was concurrent with pathology, Gene expression Biomarker studies and cellular behaviour of leukocytes in culture.

Table 1

Conclusion: MS screening using Tissue Chip platform could be employed for screening synthetic and biomolecules with picograms to nanograms concentration without compromising cellular cross talk or hormonal system in a fully functional physiological unit. Moreover these data indicate that Vasicine can be further explored as a prospective molecule in Multiple sclerosis treatment.

References:

(1) \'Tissue chip\' offers better approach to screen neural toxins https://morgridge.org/newsarticle/thomson-team-developing-tissue-chip-to-screen-developmental-toxins/

(2)Liu W et al. (2015). Phytomedicine 22: 1088-1095.