The Rogosin Institute, Xenia Division, Xenia, Ohio, USA.
Preclinical Research Center, University of Minnesota, St. Paul, Minnesota, USA.
Xenotransplantation. 2022 May;29(3):e12747. doi: 10.1111/xen.12747. Epub 2022 Apr 6.
Although human islet transplantation has proven to provide clinical benefits, especially the near complete amelioration of hypoglycemia, the supply of human islets is limited and insufficient to meet the needs of all people that could benefit from islet transplantation. Porcine islets, secreting insulin nearly identical to that of human insulin, have been proposed as a viable supply of unlimited islets. Further, encapsulation of the porcine islets has been shown to reduce or eliminate the use of immunosuppressive therapy that would be required to prevent rejection of the foreign islet tissue. The goal of the current study was to determine the long-term safety and efficacy of agarose encapsulated porcine islets (macrobeads) in diabetic cynomolgus macaques, in a study emulating a proposed IND trial in which daily exogenous insulin therapy would be reduced by 50% with no loss of glucose regulation. Four of six animals implanted with macrobeads demonstrated ≥ 30% reduction in insulin requirements in year 1 of follow-up. Animals were followed for 2, 3.5, and 7.4 years with no serious adverse events, mortality or evidence of pathogen transmission. This study supports the continued pursuit of encapsulated porcine islet therapy as a promising treatment option for diabetes mellitus.
尽管人胰岛移植已被证明能提供临床益处，尤其是几乎完全改善低血糖症，但人胰岛的供应有限，不足以满足所有可能从胰岛移植中受益的人的需求。猪胰岛分泌的胰岛素与人胰岛素几乎相同，已被提议作为一种无限供应胰岛的可行来源。此外，已证明猪胰岛的包封可以减少或消除为防止外来胰岛组织排斥而需要使用的免疫抑制疗法。目前这项研究的目的是确定琼脂糖包封的猪胰岛（大微珠）在糖尿病食蟹猴中的长期安全性和有效性，该研究模拟了一项拟议的 IND 试验，其中每日外源性胰岛素治疗将减少 50%，而不会丧失葡萄糖调节。在随访的第 1 年，6 只植入大微珠的动物中有 4 只胰岛素需求减少了≥30%。动物被随访了 2、3.5 和 7.4 年，没有严重不良事件、死亡或病原体传播的证据。这项研究支持继续探索包封的猪胰岛治疗作为糖尿病治疗的一种有前途的选择。
