Xenotransplantation for Islets from Clinical Side

Abstract

Islet transplantation can eliminate severe hypoglycemia symptoms caused by conventional treatment, and has the advantages of less trauma and complications, which is considered as the most promising treatment for type 1 diabetes mellitus (T1DM). Regulatory guidance is needed for a standard pig source. In section 1, the regulation of medical grade designed pathogen free (DPF) donor pig for clinical xenotransplantation consists of five parts: genetic quality control, microbiological surveillance, formula feeds, specification of pathological diagnosis, and requirements of environment and housing facilities. In section 2, we present the current approach and progress in pig donor selecting, pancreatic digestion, isolation and preparation of porcine islet grafts, identification and quality assessment of final islet product in clinical trials. The liver is currently the most preferred site for islet transplantation, even though it is far from ideal. A large number of alternative sites have been used for islet transplantation in experimental animal models to provide improved engraftment and long-term survival. In Section 3, we introduce some commonly used sites in xenotransplantation. The benefits and drawbacks of each parameter above are discussed in an attempt to decide which is the most suitable for clinical use and to direct future research.

Comparison of islet isolation result and clinical applicability according to GMP‐grade collagenase enzyme blend in adult porcine islet isolation and culture

“…We found that the yield of isolated islets was higher in 12‐ to 18‐month‐old pig (data not shown). For porcine islet transplantation into humans, the minimum dose is over 10 000 IEQ/kg per type 1 diabetic patient 34 . This effective dose may even be higher when using pig islets.…”

“…For porcine islet transplantation into humans, the minimum dose is over 10 000 IEQ/kg per type 1 diabetic patient. 34 This effective dose may even be higher when using pig islets. If the patient needed more islets, islet isolation from 2 or 3 porcine may be necessary 5 because of the lower insulin secretion for cure diabetes in porcine islets.…”

“…For clinical islet transplantation, the endotoxin level also plays an important role in the death of islets after transplantation. 39 In 2017, Wang et al 34 reported that the endotoxin content needed was less than 5 EU/kg recipient body weight. And in 2001, Berney et al 40 reported that the endotoxin level of the enzyme related to the islet survival–induced apoptosis and necrosis.…”