Is the renal subcapsular space the preferred site for clinical porcine islet xenotransplantation? Review article

Smood, Benjamin; Bottino, Rita; Hara, Hidetaka; Cooper, D. K. C.

doi:10.1016/j.ijsu.2019.07.032

Cited by 13 publications

(12 citation statements)

References 52 publications

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“…The kidney capsule site was chosen specifically as it is advantageous as the transplanted islets are not exposed to the blood, IBMIR is decreased, and there is less of an acute loss of beta cells upon transplantation, which is often seen in xenotransplantation. 40 Our study is the first to demonstrate the biocompatibility of this compound with functioning NPI. All diabetic NOD.SCID-Gamma mice attained normoglycemia between 6 and 12 weeks following transplantation.…”

Section: Discussionmentioning

confidence: 73%

“…The differences seen among studies are likely at least partially due to different field strengths of MRI used for imaging, and it should be noted that clinical medicine does not routinely use some of these ultra‐high field strength MRI systems due to possible health risks 42 . The ability to quantitatively detect islets in the subcapsular kidney transplant site is of particular interest with recent arguments suggesting the site could be advantageous in clinical porcine islet xenotransplantation 40 …”

Section: Discussionmentioning

confidence: 99%

“…42 The ability to quantitatively detect islets in the subcapsular kidney transplant site is of particular interest with recent arguments suggesting the site could be advantageous in clinical porcine islet xenotransplantation. 40 It should be noted that MRI monitoring of SPIO-labeled islets transplanted in the liver demonstrates a different picture. SPIO-labeled islets situated in the liver consistently demonstrated attenuated signals following rejection, and the decreasing number of islet-related hypo-attenuated MRI signals more clearly correlated with clearance of rejected islets.…”

Section: Discussionmentioning

confidence: 99%

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MRI monitoring of transplanted neonatal porcine islets labeled with polyvinylpyrrolidone‐coated superparamagnetic iron oxide nanoparticles in a mouse model

Purich

Cai

Yang

et al. 2021

Xenotransplantation

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Islet transplantation is a potential treatment option for certain patients with type 1 diabetes; however, it still faces barriers to widespread use, including the lack of tools to monitor islet grafts post‐transplantation. This study investigates whether labeling neonatal porcine islets (NPI) with polyvinylpyrrolidone‐coated superparamagnetic iron oxide nanoparticles (PVP‐SPIO) affects their function, and whether this nanoparticle can be utilized to monitor NPI xenografts with magnetic resonance imaging (MRI) in a mouse model. In vitro, PVP‐SPIO‐labeled NPI in an agarose gel was visualized clearly by MRI. PVP‐SPIO‐labeled islets were then transplanted under the kidney capsules of immunodeficient nondiabetic and diabetic mice. All diabetic mice that received transplantation of PVP‐SPIO‐labeled islets reached normoglycemia. Grafts appeared as hypo‐intense areas on MRI and were distinguishable from the surrounding tissues. Following injection of spleen cells from immunocompetent mice, normoglycemic recipient mice became diabetic and islet grafts showed an increase in volume, accompanied by a mixed signal on MRI. Overall, this study demonstrates that PVP‐SPIO did not affect the function of NPI that PVP‐SPIO‐labeled islets were easily seen on MRI, and changes in MRI signals following rejection suggest a potential use of PVP‐SPIO‐labeled islets to monitor graft viability.

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Section: Discussionmentioning

confidence: 73%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MRI monitoring of transplanted neonatal porcine islets labeled with polyvinylpyrrolidone‐coated superparamagnetic iron oxide nanoparticles in a mouse model

Purich

Cai

Yang

et al. 2021

Xenotransplantation

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“…A significant loss of islets occurs soon after transplantation resulting from several factors including complement activation and coagulation, characterized as the instant blood-mediated inflammatory reaction (IBMIR), which becomes stronger as the transplantation scenario moves from autologous to xenogeneic (5)(6)(7)(8)(9). Transplantation of islets under the kidney capsule may reduce severity of IBMIR, although loss due to inflammation, lack of nutrients, and hypoxia may still result in inconsistent engraftment (10,11). Our own in vitro data suggest that an immune response also plays a role in the early loss of islets (7,9).…”

Section: Introductionmentioning

confidence: 99%

Human Hemangioblast-Derived Mesenchymal Stem Cells Promote Islet Engraftment in a Minimal Islet Mass Transplantation Model in Mice

et al. 2021

Self Cite

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Islet transplantation can restore glycemic control in patients with type 1 diabetes. Using this procedure, the early stages of engraftment are often crucial to long-term islet function, and outcomes are not always successful. Numerous studies have shown that mesenchymal stem cells (MSCs) facilitate islet graft function. However, experimental data can be inconsistent due to variables associated with MSC generation (including donor characteristics and tissue source), thus, demonstrating the need for a well-characterized and uniform cell product before translation to the clinic. Unlike bone marrow- or adipose tissue-derived MSCs, human embryonic stem cell-derived-MSCs (hESC-MSCs) offer an unlimited source of stable and highly-characterized cells that are easily scalable. Here, we studied the effects of human hemangioblast-derived mesenchymal cells (HMCs), (i.e., MSCs differentiated from hESCs using a hemangioblast intermediate), on islet cell transplantation using a minimal islet mass model. The co-transplantation of the HMCs allowed a mass of islets that was insufficient to correct diabetes on its own to restore glycemic control in all recipients. Our in vitro studies help to elucidate the mechanisms including reduction of cytokine stress by which the HMCs support islet graft protection in vivo. Derivation, stability, and scalability of the HMC source may offer unique advantages for clinical applications, including fewer islets needed for successful islet transplantation.

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“…Islet transplantation is currently considered to be an effective method for the treatment of type 1 diabetes and certain insulin-dependent type 2 diabetes. Islet transplantation sites reported by literature mainly include the portal vein 2 , subrenal capsule 3 , splenic parenchyma (SP) 4 , 5 , omentum 6 , muscle 7 , 8 , subcutaneous 9 , 10 , gastrointestinal tract 11 , bone marrow 12 , and so on. These transplantation sites each have their own characteristics and show more or less advantages, but the optimal islet transplantation site is still controversial.…”

Section: Introductionmentioning

confidence: 99%

Comparative Study of Two Different Islet Transplantation Sites in Mice: Hepatic Sinus Tract vs Splenic Parenchyma

et al. 2020

Cell Transplant

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Although 90% of clinical islet transplantations are performed via the portal vein approach, it is still far from the ideal transplant site. Alternative islet transplant sites are promising to reduce the islet dose required to reverse hyperglycemia, thereby improving the efficiency of islet transplantation. The aim of this study was to compare the differences in survival and metabolic function of islet grafts transplanted into the hepatic sinus tract (HST) and the splenic parenchyma (SP). Approximately 300 syngeneic mouse islets were transplanted into the HST ( n = 6) and the SP ( n = 6) of recipient diabetic mice, respectively. After transplantation, the glycemic control, glucose tolerance, and morphology of islet grafts were evaluated and compared in each group. The nonfasting blood glucose of the two groups of mice receiving islet transplantation gradually decreased to the normal range and sustained for more than 100 d. There is no significant difference in the time required to restore normoglycemia ( P > 0.05). The results of the glucose tolerance test showed that the SP group presented a smaller area under the curve than the HST group ( P < 0.05). Histopathological results showed that islet grafts in the HST and the SP were characterized with normal islet morphology and robust insulin production. Compared with the HST, islet transplantation in the SP presents better blood glucose regulation, although there is no significant difference in the time required to restore normoglycemia.

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Is the renal subcapsular space the preferred site for clinical porcine islet xenotransplantation? Review article

Cited by 13 publications

References 52 publications

MRI monitoring of transplanted neonatal porcine islets labeled with polyvinylpyrrolidone‐coated superparamagnetic iron oxide nanoparticles in a mouse model

MRI monitoring of transplanted neonatal porcine islets labeled with polyvinylpyrrolidone‐coated superparamagnetic iron oxide nanoparticles in a mouse model

Human Hemangioblast-Derived Mesenchymal Stem Cells Promote Islet Engraftment in a Minimal Islet Mass Transplantation Model in Mice

Comparative Study of Two Different Islet Transplantation Sites in Mice: Hepatic Sinus Tract vs Splenic Parenchyma

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