The History of Clinical Islet Transplantation in Japan

Abstract

Islet transplantation shows the promise of being capable of relieving glucose instability and improving QOL of patients with type 1 diabetes that cannot be controlled due to severe hypoglycemia unawareness. In Japan, following the first human islet isolation from a donor after cardiac death in 2003 and the first clinical islet transplantation in 2004, islet transplantation was performed for the improvement of type 1 diabetes as a single-center trial in several centers. Although it was discontinued due to the possibility of contamination of collagenase by bovine brain component in 2007, the phase II clinical trial of islet transplantation started using ATG induction and a TNF-α inhibition protocol in 2012. The primary endpoints of this trial were the proportion of patients with HbA1c < 7.4% and freedom from severe hypoglycemic events at one year after the first islet cell infusion. In an interim analysis, this endpoint was achieved in 75% of cases. In April 2020, clinical islet transplantation was finally covered by health insurance in Japan, thanks to these outcomes. We herein introduce more than 20 years of history of clinical islet transplantation in Japan.

Clinical Islet Transplantation Covered by Health Insurance in Japan

“…Islet transplantation is a minimally invasive approach for β-cell replacement compared with pancreas transplantation. In Japan, clinical islet transplantation (CIT) has received national health insurance (NHI) coverage since April 2020 [ 6 ]. The NHI coverage of CIT is very beneficial to patients with type 1 diabetes who experience hypoglycemic unawareness despite maximal care.…”

“…In 1997, the working group of islet transplantation in the Japanese Pancreas and Islet Transplantation Association (JPITA) officially held a meeting [ 6 ]. The working group in JPITA conducted feasibility studies for the implementation of CIT in Japan and defined and standardized the donor criteria for CIT, the recipient criteria, and the facility criteria for islet isolation and CIT [ 6 ]. In 2004, we performed the first case of CIT in Japan [ 10 ].…”

“…Therefore, the law on organ transplantation with DBD was amended in 2009 and came into effect in 2010. The main modification of the law was that the declaration of a person’s intent to donate before brain death was no longer required for DBD [ 6 ]. After the law was amended, the number of DBD has gradually increased, reaching a record high of 98 cases in 2019 [ 14 ], although the number of DBD is still low compared with that in the United States and Europe.…”

“…In 2013, CIT in Japan was reopened using pancreata with DBD because of the increase in DBD from 2010. We performed the first case of CIT with DBD in Japan [ 6 ]. CIT has been performed 18 times in nine cases from 2013 to 2020 in Japan [ 6 ]; we performed CIT 15 times in this period (83% of such transplantations in Japan).…”

“…We performed the first case of CIT with DBD in Japan [ 6 ]. CIT has been performed 18 times in nine cases from 2013 to 2020 in Japan [ 6 ]; we performed CIT 15 times in this period (83% of such transplantations in Japan). The proportion of patients with HbA 1c of <7.4% without severe hypoglycemic attacks from 90 days to 365 days after the first CIT made up 75% of cases.…”