Agarose-microencapsulated Islet Xenotransplantation

Yukio Aomatsu, Yoshiyuki Nakajima, Hiromichi Kanehiro, Michiyoshi Hisanaga, Junichiro Taki, Saiho Ko, Tatsuya Kin, Kazuaki Yagura, Takao Ohyama, Kazuo Ohashi, Kazushi Nishio, Takatsugu Yamada, Hiroshige Nakano

First Department of Surgery, Nara Medical University

Pancreatic islets were microencapsulated in an agarose hydrogel as a semipermeable membrane to prevent their xenorejection. We evaluated this bioartificical pancreas in discordant xenografting with or without administration of 15-deoxyspergualin (DSG). A 5% agarose suspension containing purified canine islets was emulsified in paraffin oil and solidified by cooling in an ice-bath. Canine islets were xenotrasplanted intraperitoneally in to BALB/c mice and NOD mice rendered diabetic with streptozotocin (220 mg/kgbody weight ip) and cyclophosphamide (200 mg/kg body weight ip), respectively. Graft survivals in BALB/c mice (37±28 days) and NOD mice (31±21 days) with microencapsulation were significantly longer than those without microencapsulation used as controls. With the combination of DSG (2.5 mg/kg per day) and microencapsulation, the islet xenograft survival (76±24 days, 75±27 days) could be extended much longer and indefinite graft survival was observed in two of seven, respectively. Regardless of whether, were low doses of DSG adminisered or not, mouse anti-dog antibody titer levels of BALB/ c were elevated to more than 50% two and four weeks after xenotransplantion of microencapsulated islets; however, their plasma glucose levels remained normal. Antibody-mediated damage to microencapsulated islet could not be detected. Combined therapy by agarose-microencapsulation and administration of DSG might be a promising strategy for clinical application to prevent rejection in discordant islet xenotransplantation.

Key words
agarose-microencapsulated islet xenotransplantation, 15-deoxyspergualin, antibody titer level

Reprint requests
Yukio Aomatsu First Department of Surgery, Nara Medical University
840 Shijo-cho, Kashihara, Nara, 634 JAPAN

Accepted
December 6, 1995

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