Biology subjects

Chandran, P.

Publications and source records attributed to Chandran, P..

2 recordsLinked to original sources

bioRxiv2021

Effect of Human Mesenchymal Stem Cells on Freund's adjuvant-induced Rheumatoid Arthritis in Sprague Dawley Rats

IntroductionMesenchymal stem cells (MSC) therapy is a new approach to treat RA. Studies evaluating anti-inflammatory effects of MSCs per RA severity are scarce. Our primary objective was to evaluate anti-inflammatory effects, change in cytokine levels and cartilage regeneration of two different MSC preparations delivered through two different routes of administration in three RA stages: mild, moderate and severe. MethodsHuman-derived umbilical cord tissue MSCs (hUCT-MSCs) and human bone marrow-derived MSCs (hBM-MSCs) delivered via intra-plantar and intravenous routes were tested in Freunds adjuvant-induced arthritis in rats. Arthritis severity was based on the arthritis score (<3=mild, 3=moderate and 4=severe). Assessments included changes in arthritis scoring, paw swelling, haematology parameters, biomarkers (TNF and IL-10) and histopathology analysis. ResultsMSC treatment significantly reduced arthritis scores in all treatment groups. IL-10 levels increased 30 days after treatment with (IP)hUCT-MSCs (P=0.0241), (IV)hUCT-MSCs (P=0.0095) and (IP)hBM-MSCs (P=0.0002). TNF- levels reduced compared to positive control at 30 days: (IP)hUCT-MSCs (P=0.0060), (IV)hUCT-MSCs (P=0.0003), (IP)hBM-MSCs (P=0.0005), (IV)hBM-MSCs (P<0.0001) and continued through 30-60 days. Microscopic examination showed regenerative changes in animal joints treated with both intra-plantar or intravenous MSCs. Arthritis scores reduced in all RA severity groups while benefits (changes in IL-10 and TNF-alpha) were more pronounced in moderate and severe RA. Haematology parameters remained similar among all animal groups at baseline, 30 days and 60 days indicating safety of MSCs. ConclusionTreatment with hUCT MSCs and hBM MSCs were safe, well-tolerated and effectively reduced joint inflammation, synovial cellularity and pro-inflammatory cytokine levels in CFA-induced RA rat model.

cell biology↗

bioRxiv2020

Velcro-like mannose and slime-like sialic acid interactions guide self- adhesion and aggregation of virus N-glycan shields

The surfaces of cells and pathogens are covered with short polymers of sugars known as glycans. Complex N-glycans have a core of three mannose sugars, with distal repeats of N-acetylglucosamine and galactose sugars terminating with sialic acid (SA). Long-range slime-like and short-range Velcro-like self-adhesions were observed between SA and mannose residues, respectively, in ill-defined monolayers. We investigated if and how these adhesions translate when SA and mannose residues are presented in complex N-glycan shields on two pseudo-typed viruses brought together in force spectroscopy (FS). Slime-like adhesions were observed between the shields at higher ramp rates, whereas Velcro-like adhesions were observed at lower rates. The complex glycan shield appears penetrable at the lower ramp rates allowing the adhesion from the mannose core to be accessed; whereas the whole virus appears compressed at higher rates permitting only surface SA adhesions to be sampled. The slime-like and velcro-like adhesions were lost when SA and mannose, respectively, were cleaved with glycosidases. While virus self-adhesion in FS was modulated by glycan penetrability, virus self-aggregation in solution was only determined by the surface sugar. Mannose-terminal viruses self-aggregated in solution, while SA-terminal ones required Ca2+ ions to self-aggregate. Viruses with galactose or N-acetylglucosamine surfaces did not self-aggregate, irrespective of whether or not a mannose core was present below the N-acetylglucosamine surface. Well-defined rules appear to govern the self-adhesion and -aggregation of N-glycosylated surfaces, regardless of whether the sugars are presented in ill-defined monolayer, or N-glycan, or even polymer architecture.

biophysics↗