History of pancreas transfection

To treat a type 1 diabetic patient with uremia, the first perfused pancreas transfection was performed concurrently with a renal graft. William Kelly and Richard Lillehei conducted it in December 1966 at the University of Minnesota Hospital in Minneapolis, Minnesota. The University of Minnesota completed the first clinical transfusion of Langerhans islet cells in 1974. Pancreatic transfection was limited to a few United States and Europe centers until the 1980s. When the National Integrated Health Care (SUS, Sistema nico de Sade) legalized pancreas transplantation in Brazil at the end of the 1990s, the surgery became more popular. Edison Teixeira, a Brazilian surgeon, completed the world’s first isolation segmented pancreas transfection in 1968. In 1994, at the University of Wisconsin, the advancement of surgical procedures and the routine use of a preservation solution culminated in a considerable improvement in results and, as a result, an increase in the number of transplants conducted in numerous countries. 

Even though the pancreas transfection (reg) gene was discovered in rat regenerating islets in 1988, the protein product was first reported in the 1970s. Reg proteins are a three-subtype multigene family having a protein structure comparable to calcium-dependent lectins. Reg I and II have been linked to pancreatic growth and may be involved in maintaining beta-cell bulk in the adult pancreas. The reg III gene is activated during pancreatic inflammation, which produces pancreatitis-related protein. Reg III protein levels in the blood are sensitive to pancreatitis severity. 

Over 13 years, different laboratories independently discovered the reg proteins, which were eventually classified as a family in 1992. De Caro et al. of France reported in 1979 that a protein called “pancreatic stone protein” dominated the development of pancreatic stones in patients with chronic calcific pancreatitis. Protein deposition and plaque development within the pancreatic duct, according to the researchers, were caused by aberrant amounts of it. 

Gross and his colleagues discovered a protein naturally polymerized into high molecular weight fibrils in the extract of acid of human pancreatic cells and secretions in 1985. They named it “pancreatic thread protein” (PTP) because of its ability to undergo a globule-fibril transition between pH 5.4 and 9.2.  

Around the same time, a team led by Dr. Hiroshi Okamoto in Japan was researching an islet transfection model caused by 90 percent pancreatectomy followed by nicotinamide injection. They discovered induction of a new gene encoding a 165-amino-acid protein, which they termed “pancreatic reg,” by using depletion of RNA profiling of the transfected islets. According to Okamoto’s research, this gene was only expressed in transfected islets, not in normal pancreatic islets. It was found to be expressed in pancreatic acinar cells constantly. In humans, all three proteins—reg, PSP, and PTP—were discovered to be the same and were dubbed reg I. Reg I is also found in small amounts in the gallbladder, kidney, and stomach mucosa. 

Unno et al. identified and termed reg II a gene with 76 percent similarity to reg I. Reg II mRNA was found in the normal pancreas and transfected pancreas, but not in the normal islets, as was the case with reg I. 

Lasserre and his colleagues discovered a gene that was increased in 25% of human primary liver tumors in 1992. It was given the moniker HIP because its expression is elevated in human primary hepatocellular carcinoma, although it is generally present in the gut and pancreas. 

Yokoya and Friesen discovered a new protein in cultured rat pituitary cells that were stimulated by Human growth hormone and inhibited by secretion in 1986. This protein, known as peptide 23, is similar to PAP and thus the reg III gene’s protein product. 

Reg IIIγ, Reg IIIα, Reg IIIβ and are new members of the reg III gene family, and they correlate to the PAP I, III, and III genes isolated by Frigerio. The reg IIIα gene is currently thought to be the source of HIP and peptide 23 proteins. 

The expression of human reg IIIα mRNA is deficient in the healthy pancreas, whereas it was shown to be highly high in the normal small intestine. While reg IIIα is constantly expressed in the digestive system, reg IIIβ mRNA is not. The reg IIIγ gene is expressed throughout the small intestine and pancreas during acute pancreatitis but not in the normal pancreas.