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, Zhen; Zhan, Jinqin; Wu, Shuangshuang; Jiang, Yong; Lu, Ziwen; Sun, Shicheng; Shi, Yingying; Long, Haiting; Wei, Yanling; Yu, Wenhai; Wang, Zhihui; Liew, Soon Yi; Zhang, Yun; Sun, Weibo; Fang, Xiaofeng; Li, Yanyan; Shen, Lu; Lv, Jiayun; Sui, Weiguo; Shen, Zhongyang; Peng, Xiaozhong; Du, Yuanyuan; Deng, Hongkui

doi:10.1038/s42255-022-00713-7

Cited by 23 publications

(12 citation statements)

References 35 publications

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“…Implantation of hCiPSC-islets into the abdominal rectus sheath of diabetic monkeys restores endogenous insulin secretion and glycemic stability. [114] Currently, several stem cell-based therapies for diabetes have already entered clinical trials. One notable trial (No.…”

Section: Generation Of β β-Cells From Human Pluripotent Stem Cells (H...mentioning

confidence: 99%

Pancreatic β-cell failure, clinical implications, and therapeutic strategies in type 2 diabetes

Cui,

Feng,

Lei

et al. 2024

Chinese Medical Journal

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Pancreatic β-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes (T2D). Reserving insulin-producing β-cells and hence restoring insulin production are gaining attention in translational diabetes research, and β-cell replenishment has been the main focus for diabetes treatment. Significant findings in β-cell proliferation, transdifferentiation, pluripotent stem cell differentiation, and associated small molecules have served as promising strategies to regenerate β-cells. In this review, we summarize current knowledge on the mechanisms implicated in β-cell dynamic processes under physiological and diabetic conditions, in which genetic factors, age-related alterations, metabolic stresses, and compromised identity are critical factors contributing to β-cell failure in T2D. The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promoting β-cell proliferation, inducing non-β-cell transdifferentiation, and reprograming stem cell differentiation. Although a significant challenge remains for each of these strategies, the recognition of the mechanisms responsible for β-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenous β-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

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Section: Generation Of β β-Cells From Human Pluripotent Stem Cells (H...mentioning

confidence: 99%

Pancreatic β-cell failure, clinical implications, and therapeutic strategies in type 2 diabetes

Cui,

Feng,

Lei

et al. 2024

Chinese Medical Journal

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“…Starting from 6 weeks post-transplantation (WPT), C-peptide secretion responds to feeding challenges, with a stimulation index equivalent to primary islets. From the eighth week, the average postprandial C-peptide level reached about 2 ng/mL−1, which is 5 times the peak obtained after portal vein infusion of hPSC-islets and is related to a 44 % reduction in glycated hemoglobin level at 12 weeks [ 82 ]. A recent study showed that insulin-producing cells (IPCs) differentiated from human MSCs and transplanted via the portal vein into a non-human primate tree shrew model of diabetes rapidly reduced blood glucose levels to near-normal levels and remained significantly lower than the MSC group or saline group over the subsequent 3 weeks [ 83 ].…”

Section: Validating the Safety And Efficacy Of Cellular Therapies Bas...mentioning

confidence: 99%

“…In the field of diabetes cell therapy, treatment protocols have evolved as well. The anterior rectus sheath is now considered a more optimal transplantation site as it effectively supports the survival and long-term function of pancreatic islet cells [ 124 ]. Moreover, the surgery for transplantation at this site is safer and more convenient, allowing for monitoring and management via medical imaging.…”

Section: Validating the Safety And Efficacy Of Cellular Therapies Bas...mentioning

confidence: 99%

Current state of stem cell research in non-human primates: an overview

Wu,

Shi,

Yang

et al. 2023

Medical Review

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The remarkable similarity between non-human primates (NHPs) and humans establishes them as essential models for understanding human biology and diseases, as well as for developing novel therapeutic strategies, thereby providing more comprehensive reference data for clinical treatment. Pluripotent stem cells such as embryonic stem cells and induced pluripotent stem cells provide unprecedented opportunities for cell therapies against intractable diseases and injuries. As continue to harness the potential of these biotechnological therapies, NHPs are increasingly being employed in preclinical trials, serving as a pivotal tool to evaluate the safety and efficacy of these interventions. Here, we review the recent advancements in the fundamental research of stem cells and the progress made in studies involving NHPs.

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“…Zhen Liang and colleagues successfully implanted human pluripotent stem cell-derived islets into the abdominal transplantation site - the rectus sheath of eight non-human primates (5 males and 3 females), improving blood glucose control in diabetic primates ( 160 ).…”

Section: Non- Hepatic Transplant Sitementioning

confidence: 99%

Challenges and opportunities in the islet transplantation microenvironment: a comprehensive summary of inflammatory cytokine, immune cells, and vascular endothelial cells

Chen,

Liu,

Zhao

et al. 2023

Front. Immunol.

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It is now understood that islet transplantation serves as a β-cell replacement therapy for type 1 diabetes. Many factors impact the survival of transplanted islets, especially those related to the microenvironment. This review explored microenvironmental components, including vascular endothelial cells, inflammatory cytokines, and immune cells, and their profound effects on post-islet transplantation survival rates. Furthermore, it revealed therapeutic strategies aimed at targeting these elements. Current evidence suggests that vascular endothelial cells are pivotal in facilitating vascularization and nutrient supply and establishing a new microcirculation network for transplanted islets. Consequently, preserving the functionality of vascular endothelial cells emerges as a crucial strategy to enhance the survival of islet transplantation. Release of cytokines will lead to activation of immune cells and production and release of further cytokines. While immune cells hold undeniable significance in regulating immune responses, their activation can result in rejection reactions. Thus, establishing immunological tolerance within the recipient’s body is essential for sustaining graft functionality. Indeed, future research endeavors should be directed toward developing precise strategies for modulating the microenvironment to achieve higher survival rates and more sustained transplantation outcomes. While acknowledging certain limitations inherent to this review, it provides valuable insights that can guide further exploration in the field of islet transplantation. In conclusion, the microenvironment plays a paramount role in islet transplantation. Importantly, we discuss novel perspectives that could lead to broader clinical applications and improved patient outcomes in islet transplantation.

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Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets

Cited by 23 publications

References 35 publications

Pancreatic β-cell failure, clinical implications, and therapeutic strategies in type 2 diabetes

Pancreatic β-cell failure, clinical implications, and therapeutic strategies in type 2 diabetes

Current state of stem cell research in non-human primates: an overview

Challenges and opportunities in the islet transplantation microenvironment: a comprehensive summary of inflammatory cytokine, immune cells, and vascular endothelial cells

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