Feasibility of islet magnetic resonance imaging using ferumoxytol in intraportal islet transplantation

Jin, Sang‐Man; Oh, Seung-Hoon; Oh, Bong Ryoul; Shim, Wooyoung; Choi, Jin Kyeong; Yoo, Dongkyeom; Hwang, Yong Hwa; Lee, Jun Young; Lee, Dong Yun; Kim, Jae Hyun

doi:10.1016/j.biomaterials.2015.02.055

Cited by 10 publications

(10 citation statements)

References 19 publications

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“…Moreover, when F and P were administered intravenously experimentally there was no evidence of uptake in circulating leukocytes[35]. Pancreatic islet cells could be labeled with high concentrations of F without toxicity with the islets after intraportal vein injection being detected in the mouse liver as hypointense regions for up to 2wks[36]. Rat bone marrow MSCs were reported to endocytose F in vivo and these cells could then be isolated and expanded ex vivo for subsequent implantation used to treat damaged cartilage[37].…”

Section: Discussionmentioning

confidence: 99%

Physicochemical characterization of ferumoxytol, heparin and protamine nanocomplexes for improved magnetic labeling of stem cells

Bryant

Kim

Hobson

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

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Stem cell-based therapies have become a major focus in regenerative medicine and to treat diseases. A straightforward approach combining three drugs, heparin (H), protamine (P) with ferumoxytol (F) in the form of nanocomplexes (NCs) effectively labeled stem cells for cellular MRI. We report on the physicochemical characteristics for optimizing the H, P, and F components in different ratios, and mixing sequences, producing NCs that varied in hydrodynamic size. NC size depended on the order in which drugs were mixed in media. Electron microscopy of HPF or FHP showed that F was located on the surface of spheroidal shaped HP complexes. Human stem cells incubated with FHP NCs resulted in a significantly greater iron concentration per cell compared to that found in HPF NCs with the same concentration of F. These results indicate that FHP could be useful for labeling stem cells in translational studies in the clinic.

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Section: Discussionmentioning

confidence: 99%

Physicochemical characterization of ferumoxytol, heparin and protamine nanocomplexes for improved magnetic labeling of stem cells

Bryant

Kim

Hobson

et al. 2017

Nanomedicine: Nanotechnology, Biology and Medicine

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“…These clusters could be clearly visualized if at least 50 ML-labelled pancreatic islets were engrafted (detection threshold). To our knowledge, the minimal amount of islets previously detected by in vivo MRI after pre-labelling with iron oxide based nanoparticles followed by intraportal transplantation was 300 islet equivalents (IEQ) at 7 T 40 and 230 islets performed at 3 T 21 . The use of MLs improves the sensitivity of in vivo monitoring of engrafted pancreatic islets substantially.…”

Section: Discussionmentioning

confidence: 99%

“…g ., for 48 hrs) 39 . In studies performed with Feridex®, it was possible to reduce the incubation times to overnight 13 and even 1 hr 40 by using either higher concentrations of iron oxide (200 µg Fe/ml) or by chemically conjugating the contrast agent directly onto the islet surface, respectively. Here, we propose a direct method for labelling of pancreatic islets without the utilization of transfection agents or further modifications to the islets themselves, at a very low iron oxide concentration (50 µg Fe/mL), which results in a high intracellular iron uptake and excellent T2/T2* MRI contrast.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, these images are not directly quantifiable. A number of approaches have been investigated to obtain positive contrast from SPIOs, including ultrashort echo time (UTE) MR imaging 40 – 42 . UTE MRI offers a relatively simple strategy by taking advantage of relatively high longitudinal relaxivities (r1) of SPIOs while reducing the contribution of predominant T2 and T2* contrast.…”

Section: Discussionmentioning

confidence: 99%

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Magnetoliposomes as Contrast Agents for Longitudinal in vivo Assessment of Transplanted Pancreatic Islets in a Diabetic Rat Model

Ribeiro¹,

Gysemans

Cunha

et al. 2018

Sci Rep

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Magnetoliposomes (MLs) were synthesized and tested for longitudinal monitoring of transplanted pancreatic islets using magnetic resonance imaging (MRI) in rat models. The rat insulinoma cell line INS-1E and isolated pancreatic islets from outbred and inbred rats were used to optimize labeling conditions in vitro. Strong MRI contrast was generated by islets exposed to 50 µg Fe/ml for 24 hours without any increased cell death, loss of function or other signs of toxicity. In vivo experiments showed that pancreatic islets (50–1000 units) labeled with MLs were detectable for up to 6 weeks post-transplantation in the kidney subcapsular space. Islets were also monitored for two weeks following transplantation through the portal vein of the liver. Hereby, islets labeled with MLs and transplanted under the left kidney capsule were able to correct hyperglycemia and had stable MRI signals until nephrectomy. Interestingly, in vivo MRI of streptozotocin induced diabetic rats transplanted with allogeneic islets demonstrated loss of MRI contrast between 7–16 days, indicative of loss of islet structure. MLs used in this study were not only beneficial for monitoring the location of transplanted islets in vivo with high sensitivity but also reported on islet integrity and hereby indirectly on islet function and rejection.

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“…Therefore, noninvasive islet follow-up studies using magnetic resonance imaging (MRI) or computed tomography (CT) have been extensively performed and demonstrate the importance and risks of indirect liver biopsy [20][21][22][23][24][25][26][27][28] .…”

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confidence: 99%

Integrated whole liver histologic analysis of the allogeneic islet distribution and characteristics in a nonhuman primate model

Kim

Lee²,

Shin

et al. 2020

Sci Rep

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The most obvious method to observe transplanted islets in the liver is direct biopsy, but the distribution and location of the best biopsy site in the recipient's liver are poorly understood. islets transplanted into the whole liver of five diabetic cynomolgus monkeys that underwent insulin-independent survival for an extended period of time after allo-islet transplantation were analyzed for characteristics and distribution tendency. The liver was divided into segments (S1-S8), and immunohistochemistry analysis was performed to estimate the diameter, beta cell area, and islet location. Islets were more distributed in S2 depending on tissue size; however, the number of islets per tissue size was high in S1 and S8. Statistical analysis revealed that the characteristics of islets in S1 and S8 were relatively similar to other segments despite various transplanted islet dosages and survival times. In conclusion, S1, which exhibited high islet density and reflected the overall characteristics of transplanted islets, can be considered to be a reasonable candidate for a liver biopsy site in this monkey model. The findings obtained from the five monkey livers with similar anatomical features to human liver can be used as a reference for monitoring transplanted islets after clinical islet transplantation.

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Feasibility of islet magnetic resonance imaging using ferumoxytol in intraportal islet transplantation

Cited by 10 publications

References 19 publications

Physicochemical characterization of ferumoxytol, heparin and protamine nanocomplexes for improved magnetic labeling of stem cells

Physicochemical characterization of ferumoxytol, heparin and protamine nanocomplexes for improved magnetic labeling of stem cells

Magnetoliposomes as Contrast Agents for Longitudinal in vivo Assessment of Transplanted Pancreatic Islets in a Diabetic Rat Model

Integrated whole liver histologic analysis of the allogeneic islet distribution and characteristics in a nonhuman primate model

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