Hybrid Congregation of Islet Single Cells and Curcumin-Loaded Polymeric Microspheres as an Interventional Strategy to Overcome Apoptosis Associated with Pancreatic Islets Transplantation.
Hypoxic or near-anoxic conditions that occur in the core of transplanted islets induce necrosis and apoptosis during the early stages after transplantation, primarily due to loss of vascularization during the isolation process. Moreover, secretion of various cytokines from pancreatic islets is detrimental to the viability of islet cells in vitro. In this study, we aimed to protect pancreatic islet cells against apoptosis by establishing a method for in situ delivery of curcumin to the pancreatic islets. Self-assembled heterospheroids composed of pancreatic islet cells and curcumin-loaded polymeric microspheres were prepared by the three-dimensional cell culture technique. Release of curcumin in the microenvironment of pancreatic islets promoted survival of the islets. In hypoxic culture conditions, which mimic the in vivo conditions after transplantation, viability of the islets was significantly improved, as indicated by a decreased expression of pro-apoptotic protein and an increased expression of anti-apoptotic protein. Additionally, oxidative stress-induced cell death was suppressed. Thus, unlike co-transplantation of pancreatic islets and free microspheres, which provided a wide distribution of microspheres throughout the transplanted area, the heterospheroid transplantation resulted in colocalization of pancreatic islet cells and microspheres, thereby exerting beneficial effects on the cells.
College of Pharmacy, Yeungnam University , Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Shiva
S
Pathak
College of Pharmacy, Yeungnam University , Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Shobha
S
Regmi
College of Pharmacy, Yeungnam University , Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Biki
B
Gupta
College of Pharmacy, Yeungnam University , Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Bijay K
BK
Poudel
College of Pharmacy, Yeungnam University , Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Tung Thanh
TT
Pham
Department of Biochemistry and Molecular Biology and Smart-Aging Convergence Research Center, College of Medicine, Yeungnam University , Daegu 42415, Republic of Korea.
Jae-Ryong
JR
Kim
College of Pharmacy, Yeungnam University , Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Pil-Hoon
PH
Park
College of Pharmacy, Yeungnam University , Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Chul Soon
CS
Yong
College of Pharmacy, Yeungnam University , Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Jong Oh
JO
Kim
Department of Pathology, Yeungnam University College of Medicine , Daegu 42415, Republic of Korea.
Young Kyung
YK
Bae
Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF) , Daegu 41061, Republic of Korea.
Sang Kyoon
SK
Kim
College of Pharmacy, Yeungnam University , Gyeongsan, Gyeongbuk 38541, Republic of Korea.
Jee-Heon
JH
Jeong
D017209:Apoptosis; D003474:Curcumin; D007515:Islets of Langerhans; D016381:Islets of Langerhans Transplantation; D008863:Microspheres
D003474:Curcumin
anti-apoptosis; colocalization; curcumin; heterospheroids; islets transplantation; poly(lactic-co-glycolic acid) microspheres