Bioengineered omental transplant site promotes pancreatic islet allografts survival in non-human primates

Deng, Hongping; Zhang, Alexander; Pang, Dillon Ren Rong; Xi, Yinsheng; Yang, Zhihong; Matheson, Rudy; Li, Guoping; Luo, Hao; Lee, Kang M.; Fu, Qiang; Zou, Zhongliang; Chen, Tao; Wang, Zhenjuan; Rosales, Ivy A.; Peters, Cole W.; Yang, Jie; Coronel, María M.; Yolcu, Esma S.; Shirwan, Haval; Garcı́a, Andrés J.; Markmann, James F.; Ji, Lei

doi:10.1016/j.xcrm.2023.100959

Cited by 12 publications

(10 citation statements)

References 49 publications

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“…A recent study by Deng et al. 57 confirmed that the omental transplant site successfully promoted the survival of islet allografts and resulted in euglycemia in three diabetic NHPs.…”

Section: Discussionmentioning

confidence: 89%

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Short‐term function and immune‐protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non‐human primates without systemic immune suppression: A pilot study

Sremac,

Luo,

Deng

et al. 2023

Xenotransplantation

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Replacement of insulin‐producing pancreatic beta‐cells by islet transplantation offers a functional cure for type‐1 diabetes (T1D). We recently demonstrated that a clinical grade alginate micro‐encapsulant incorporating the immune‐repellent chemokine and pro‐survival factor CXCL12 could protect and sustain the integrity and function of autologous islets in healthy non‐human primates (NHPs) without systemic immune suppression. In this pilot study, we examined the impact of the CXCL12 micro encapsulant on the function and inflammatory and immune responses of xenogeneic islets transplanted into the omental tissue bilayer sac (OB; n = 4) and diabetic (n = 1) NHPs. Changes in the expression of cytokines after implantation were limited to 2–6‐fold changes in blood, most of which did not persist over the first 4 weeks after implantation. Flow cytometry of PBMCs following transplantation showed minimal changes in IFNγ or TNFα expression on xenoantigen‐specific CD4+ or CD8+ T cells compared to unstimulated cells, and these occurred mainly in the first 4 weeks. Microbeads were readily retrievable for assessment at day 90 and day 180 and at retrieval were without microscopic signs of degradation or foreign body responses (FBR). In vitro and immunohistochemistry studies of explanted microbeads indicated the presence of functional xenogeneic islets at day 30 post transplantation in all biopsied NHPs. These results from a small pilot study revealed that CXCL12‐microencapsulated xenogeneic islets abrogate inflammatory and adaptive immune responses to the xenograft. This work paves the way toward future larger scale studies of the transplantation of alginate microbeads with CXCL12 and porcine or human stem cell‐derived beta cells or allogeneic islets into diabetic NHPs without systemic immunosuppression.

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“…A recent study by Deng et al. 57 confirmed that the omental transplant site successfully promoted the survival of islet allografts and resulted in euglycemia in three diabetic NHPs.…”

Section: Discussionmentioning

confidence: 89%

“…We monitored CXCL12 levels in small and large preclinical animal models . [10][11][12][13]25,26 A recent study by Deng et al 57 confirmed that the omental transplant site successfully promoted the survival of islet allografts and resulted in euglycemia in three diabetic NHPs.…”

Section: Cxcl12 Release From Microbeadsmentioning

confidence: 91%

Short‐term function and immune‐protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non‐human primates without systemic immune suppression: A pilot study

Sremac,

Luo,

Deng

et al. 2023

Xenotransplantation

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“…Typically, around 3,000 islet equivalents (IEQ) per mouse and www.e-enm.org 195 approximately 100,000 IEQ per kilogram of body weight in humans are required to observe a beneficial effect on glucose homeostasis in diabetes (Table 1) [4,5,[10][11][12][61][62][63][64][65][66][67][68][69][70][71][72][73][74][75]. Consequently, a strategic expansion of fully mature and functionally homogeneous β cells is necessary to standardize these therapeutic interventions.…”

Section: Expansion and Scalabilitymentioning

confidence: 99%

“…This can be accomplished primarily through two approaches: increasing the number of endogenous β cells or transplanting β cells from external sources. Stem cellbased islet replacement therapy has emerged as a curative ap-proach for insulin-dependent diabetes mellitus (IDDM) across several preclinical animal studies [4][5][6][7][8][9][10][11][12] and human trials [13][14][15]. In 2000, the capabilities of islet replacement therapy were demonstrated by a hallmark islet transplantation study, wherein all seven patients with type 1 diabetes (T1D) who underwent transplantation with islets from cadaveric donors became insulin-independent for a minimum duration of 1 year [16].…”

Section: Introductionmentioning

confidence: 99%

Scaling Insulin-Producing Cells by Multiple Strategies

Choi,

Cayabyab,

Perez

et al. 2024

Endocrinol Metab

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In the quest to combat insulin-dependent diabetes mellitus (IDDM), allogenic pancreatic islet cell therapy sourced from deceased donors represents a significant therapeutic advance. However, the applicability of this approach is hampered by donor scarcity and the demand for sustained immunosuppression. Human induced pluripotent stem cells are a game-changing resource for generating synthetic functional insulin-producing β cells. In addition, novel methodologies allow the direct expansion of pancreatic progenitors and mature β cells, thereby circumventing prolonged differentiation. Nevertheless, achieving practical reproducibility and scalability presents a substantial challenge for this technology. As these innovative approaches become more prominent, it is crucial to thoroughly evaluate existing expansion techniques with an emphasis on their optimization and scalability. This manuscript delineates these cutting-edge advancements, offers a critical analysis of the prevailing strategies, and underscores pivotal challenges, including cost-efficiency and logistical issues. Our insights provide a roadmap, elucidating both the promises and the imperatives in harnessing the potential of these cellular therapies for IDDM.

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“…The omentum is an attractive extrahepatic alternative site for clinical islet transplantation, researchers have explored a method to transplant allogeneic islets to the omentum, and in three types of diabetic NHPs, the omentum is bioengineered with plasma-thrombin biodegradable matrix. Within a week after transplantation, each transplanted NHPs reached normoglycemia and insulin dependence, and remained stable [ 84 ].…”

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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Bioengineered omental transplant site promotes pancreatic islet allografts survival in non-human primates

Cited by 12 publications

References 49 publications

Short‐term function and immune‐protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non‐human primates without systemic immune suppression: A pilot study

Short‐term function and immune‐protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non‐human primates without systemic immune suppression: A pilot study

Scaling Insulin-Producing Cells by Multiple Strategies

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

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