Curative role of mesenchymal stromal cells in chronic pancreatitis: Modulation of MAPK and TGF-β1/SMAD factors

Abstract

Background and objective: Living organisms respond to physical, chemical, and biological threats with a potent inflammatory response which alters organ cell signaling and leads to dysfunction. We evaluated the therapeutic effect of bone marrow-based mesenchymal stromal cell (BM-MSC) transplanted in rats to preserve tissue integrity and to restore homeostasis and function in the pancreatitis experimental pattern. Methods: This study involved 40 adult male Wister rats. Repeated L-arginine injections caused chronic pancreatitis (CP), leading to the development of pancreatic damage and shifting the intracellular signaling pathways. Rats were then infused with BM-MSC labeled with PKH26 fluorescent linker dye for 12 weeks. Results: Cell-surface indicators of BM-MSCs such as CD 90 and CD29 were expressed with the lack of CD34 expression. BM-MSC treatment considerably improved the alterations induced in a series of inflammatory markers, including IL-18, TNF-α, CRP, PGE2, and MCP-1. Furthermore, improvement was found in digestive enzymes and lipid profile with amelioration in myeloperoxidase activity. BM-MSC treatment also regulated the (TGF-/p-38MPAK/SMAD2/3) signaling factors that enhances repair of damaged pancreatic tissue, confirmed by reversed alteration of histopathological examination. Conclusion: our results further bring to light the promise of cell transplant therapy for chronic pancreatitis.

The research progress of anti-inflammatory and anti-fibrosis treatment of chronic pancreatitis

“…Studies have shown that a large number of inflammatory factors, such as IL-18, TNF-α, and growth factor TGF-B1 are significantly reduced in animal models of CP treated with MSCs, and tissue immune cell infiltration is alleviated. In vitro experiments also showed that when co-cultured with MSCs, the production of inflammatory factors in acinar cells and PSCs was inhibited and the inflammatory response of macrophages was reduced ( 65 – 70 ).…”

“…Pancreatic histopathology showed that MSC treatment improved collagen deposition, repaired damaged cells and Langerhans giant cells, reduced the expression of α-SMA, and reduced immune cell infiltration. Serum analysis showed that MSCs affected ECM metabolism by decreasing levels of hyaluronic acid and fibronectin ( 69 , 70 ). Activation of PSCs is a key link that leads to pancreatic fibrosis.…”

“…Compared with the untreated group, the decrease of protein expression and amylase activity in the pancreas during CP was reversed after MSC treatment, and abnormally elevated serum pancreatic enzyme levels decreased. Therefore, MSC treatment can improve exocrine function and attenuate the pancreatic injury caused by CP ( 70 ).…”

“…proposed that normalization of the lipid profile of the MSC-treated subjects was achieved by improving β-c ell function and insulin resistance. MSCs can also secrete bioactive factors and differentiate into β-c ells to rescue pancreatic endocrine function ( 70 , 71 ).…”

Immortalized Mesenchymal Stromal Cells Overexpressing Alpha-1 Antitrypsin Protect Acinar Cells from Apoptotic and Ferroptotic Cell Death

“…Mesenchymal stromal cells (MSCs) have therapeutic potential due to their immunoregulatory and antiin ammatory effects [15][16][17][18]. Overexpressing alpha-1 antitrypsin (AAT) in MSCs shows promise in antiin ammatory properties.…”