ABSTRACT
BACKGROUND@#Tissue engineering centers on creating a niche similar to the natural one, with a purpose of developing an organ construct. A natural scaffold can replace none while creating a scaffold unique to each tissue in composition, architecture and cues that regulate the character of cells. @*METHODS@#Whole pancreas from mouse was decellularized using detergent and enzymes, followed by recellularizing with MSC from human placenta. This construct was transplanted in streptozotocin induced diabetic mice. Histopathology of both decellularized and recellularized transplanted pancreas and qPCR analysis were performed to assess its recovery. @*RESULTS@#Decellularization removes the cells leaving behind extracellular matrix rich natural scaffold. After reseeding with mesenchymal stem cells, these cells differentiate into pancreas specific cells. Upon transplantation in streptozotocin induced diabetic mice, this organ was capable of restoring its histomorphology and functioning. Restoration of endocrine (islets), the exocrine region (acinar) and vascular network was seen in transplanted pancreas. The process of functional recovery of endocrine system took about 20 days when the mice start showing blood glucose reduction, though none achieved gluconormalization. @*CONCLUSION@#Natural decellularized scaffolds of soft organs can be refunctionalized using recipient’s mesenchymal stem cells to restore structure and function; and counter immune problems arising during transplantation.
ABSTRACT
BACKGROUND@#Tissue engineering centers on creating a niche similar to the natural one, with a purpose of developing an organ construct. A natural scaffold can replace none while creating a scaffold unique to each tissue in composition, architecture and cues that regulate the character of cells. @*METHODS@#Whole pancreas from mouse was decellularized using detergent and enzymes, followed by recellularizing with MSC from human placenta. This construct was transplanted in streptozotocin induced diabetic mice. Histopathology of both decellularized and recellularized transplanted pancreas and qPCR analysis were performed to assess its recovery. @*RESULTS@#Decellularization removes the cells leaving behind extracellular matrix rich natural scaffold. After reseeding with mesenchymal stem cells, these cells differentiate into pancreas specific cells. Upon transplantation in streptozotocin induced diabetic mice, this organ was capable of restoring its histomorphology and functioning. Restoration of endocrine (islets), the exocrine region (acinar) and vascular network was seen in transplanted pancreas. The process of functional recovery of endocrine system took about 20 days when the mice start showing blood glucose reduction, though none achieved gluconormalization. @*CONCLUSION@#Natural decellularized scaffolds of soft organs can be refunctionalized using recipient’s mesenchymal stem cells to restore structure and function; and counter immune problems arising during transplantation.
ABSTRACT
Objective: To investigate the therapeutic efficacy of andrographolide, a plant derived compound, against chikungunya virus (CHIKV) infection. Methods: Using flow cytometry and immunoblotting assay, in vitro viral protein expression was studied in THP-1 cells line. In Balb/c mouse neonates, viral RNA copy number was determined by real time PCR. Results: The results showed reduced CHIKV protein expression on andrographolide treatment in CHIKV-infected human peripheral blood mononuclear cells, Vero cells and THP-1 cell line. In vivo, andrographolide treatment to CHIKV-infected neonates reduced viral RNA copy number. Further, andrographolide also increased cytotoxic T lymphocytes both in vitro and in vivo. Andrographolide also activated host innate immune pathways, viz., protein kinase R, phosphorylated eukaryotic initiation factor 2α , retinoic acid inducible gene-I and interferon regulatory factor 3/7, thereby increasing IFN- α secretion. CHIKV-induced nuclear factor κ light chain enhancer of activated B cells and tumor necrosis factor- α was also reduced on andrographolide treatment. Conclusion: Andrographolide inhibits CHIKV by suppressing viral protein expression and up-regulating host innate immunity and hence could be an effective therapeutic agent against CHIKV infection.