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Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets.
Liang, Zhen; Sun, Dong; Lu, Shuaiyao; Lei, Zhengjun; Wang, Shusen; Luo, Zhifeng; Zhan, Jinqin; Wu, Shuangshuang; Jiang, Yong; Lu, Zhi; Sun, Shicheng; Shi, Yingying; Long, Haiting; Wei, Yanling; Yu, Wenhai; Wang, Zhihui; Yi, Liew Soon; Zhang, Yun; Sun, Wenyong; Fang, Xiaofeng; Li, Yanyan; Lu, Sufang; Lv, Jiayun; Sui, Weiguo; Shen, Zhongyang; Peng, Xiaozhong; Du, Yuanyuan; Deng, Hongkui.
Afiliación
  • Liang Z; MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Ce
  • Sun D; Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • Lu S; MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Ce
  • Lei Z; State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
  • Wang S; Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • Luo Z; Organ Transplant Center, NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, China.
  • Zhan J; The Second Department of Urology, Affiliated Hospital of Guilin Medical University, Guilin, China.
  • Wu S; Ultrasonic Department, First Affiliated Hospital of Kunming Medical University, Kunming, China.
  • Jiang Y; Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • Lu Z; Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • Sun S; Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • Shi Y; MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Ce
  • Long H; Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • Wei Y; Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Yu W; Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • Wang Z; Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Yi LS; Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • Zhang Y; MOE Engineering Research Center of Regenerative Medicine, School of Basic Medical Sciences, State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center and the MOE Key Laboratory of Cell Proliferation and Differentiation, College of Life Sciences, Peking-Tsinghua Ce
  • Sun W; Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • Fang X; Hangzhou Repugene Technology, Hangzhou, China.
  • Li Y; Hangzhou Repugene Technology, Hangzhou, China.
  • Lu S; Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China.
  • Lv J; Hangzhou Reprogenix Bioscience, Hangzhou, China.
  • Sui W; Hangzhou Repugene Technology, Hangzhou, China.
  • Shen Z; The Second Department of Urology, Affiliated Hospital of Guilin Medical University, Guilin, China.
  • Peng X; Organ Transplant Center, NHC Key Laboratory for Critical Care Medicine, Tianjin First Central Hospital, Nankai University, Tianjin, China.
  • Du Y; State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Medical Primate Research Center, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
  • Deng H; Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Yunnan, China. pengxiaozhong@pumc.edu.cn.
Nat Metab ; 5(1): 29-40, 2023 01.
Article en En | MEDLINE | ID: mdl-36624157
Human pluripotent stem cell-derived islets (hPSC islets) are a promising alternative to primary human islets for the treatment of insulin-deficient diabetes. We previously demonstrated the feasibility of this approach in nonhuman primates; however, the therapeutic effects of hPSC islets can be limited by the maladaptive processes at the transplantation site. Here, we demonstrate successful implantation of hPSC-derived islets in a new transplantation site in the abdomen, the subanterior rectus sheath, in eight nonhuman primates (five male and three female). In this proof-of-principle study, we find that hPSC islets survive and gradually mature after transplantation, leading to improved glycemic control in diabetic primates. Notably, C-peptide secretion responds to meal challenge from 6 weeks post-transplantation (wpt), with stimulation indices comparable to those of native islets. The average post-prandial C-peptide level reaches approximately 2.0 ng ml-1 from 8 wpt, which is five times higher than the peak value we previously obtained after portal vein infusion of hPSC islets and was associated with a decrease of glycated hemoglobin levels by 44% at 12 wpt. Although additional studies in larger cohorts involving long-term follow-up of transplants are needed, our results indicate that the subanterior rectus sheath supports functional maturation and maintenance of hPSC islets, suggesting that it warrants further exploration as a transplantation target site in the context of for hPSC-based cell-replacement therapies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Islotes Pancreáticos / Islotes Pancreáticos Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Metab Año: 2023 Tipo del documento: Article Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
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PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Trasplante de Islotes Pancreáticos / Islotes Pancreáticos Límite: Animals / Female / Humans / Male Idioma: En Revista: Nat Metab Año: 2023 Tipo del documento: Article Pais de publicación: Alemania