Abstract:, "Photoacoustic imaging of angiogenesis in a subcutaneous islet transplant site in a murine model," J. Biomed. Opt. 21(6), 066003 (2016), doi: 10.1117/1.JBO.21.6.066003. Abstract. Islet transplantation (IT) is an established clinical therapy for select patients with type-1 diabetes. Clinically, the hepatic portal vein serves as the site for IT. Despite numerous advances in clinical IT, limitations remain, including early islet cell loss posttransplant, procedural complications, and the inability to effectivel… Show more
“…[72][73][74] However, given the financial cost of lectin and how lectin delivery is traditionally based on body weight, 26 a more cost-effective procedure for large animal models is desired. Photoacoustic imaging, 75 ultrasound imaging, 76,77 and positron emission topography 78 are noninvasive techniques that have been employed for the longitudinal tracking of organ blood flow and angiogenesis in the subcutaneous space of rodents; 79,80 although equipment costs and access, low imaging depth, and low spatial resolution are common constraints. 82 The excellent correlation between our microsphere perfusion data and quantified immunostaining validates the utility of this terminal fluorescent microsphere perfusion technique in the subcutaneous space.…”
Section: Fluorescent Microsphere Perfusion For Porcine Subcutaneous T...mentioning
For cell therapies, the subcutaneous space is an attractive transplant site due to its large surface area and accessibility for implantation, monitoring, biopsy, and retrieval. However, its poor vascularization has catalyzed research to induce blood vessel formation within the site to enhance cell revascularization and survival. Most studies focus on the subcutaneous space of rodents, which does not recapitulate important anatomical features and vascularization responses of humans. Herein, we evaluate biomaterial‐driven vascularization in the porcine subcutaneous space. Additionally, we report the first use of cost‐effective fluorescent microspheres to quantify perfusion in the porcine subcutaneous space. We investigate the vascularization‐inducing efficacy of vascular endothelial growth factor (VEGF)‐delivering synthetic hydrogels based on 4‐arm poly(ethylene) glycol macromers with terminal maleimides (PEG‐4MAL). We compare three groups: a non‐degradable hydrogel with a VEGF‐releasing PEG‐4MAL gel coating (Core+VEGF gel); an uncoated, non‐degradable hydrogel (Core‐only); and naïve tissue. After 2 weeks, Core+VEGF gel has significantly higher tissue perfusion, blood vessel area, blood vessel density, and number of vessels compared to both Core‐only and naïve tissue. Furthermore, healthy vital signs during surgery and post‐procedure metrics demonstrate the safety of hydrogel delivery. We demonstrate that VEGF‐delivering synthetic hydrogels induce robust vascularization and perfusion in the porcine subcutaneous space.
“…[72][73][74] However, given the financial cost of lectin and how lectin delivery is traditionally based on body weight, 26 a more cost-effective procedure for large animal models is desired. Photoacoustic imaging, 75 ultrasound imaging, 76,77 and positron emission topography 78 are noninvasive techniques that have been employed for the longitudinal tracking of organ blood flow and angiogenesis in the subcutaneous space of rodents; 79,80 although equipment costs and access, low imaging depth, and low spatial resolution are common constraints. 82 The excellent correlation between our microsphere perfusion data and quantified immunostaining validates the utility of this terminal fluorescent microsphere perfusion technique in the subcutaneous space.…”
Section: Fluorescent Microsphere Perfusion For Porcine Subcutaneous T...mentioning
For cell therapies, the subcutaneous space is an attractive transplant site due to its large surface area and accessibility for implantation, monitoring, biopsy, and retrieval. However, its poor vascularization has catalyzed research to induce blood vessel formation within the site to enhance cell revascularization and survival. Most studies focus on the subcutaneous space of rodents, which does not recapitulate important anatomical features and vascularization responses of humans. Herein, we evaluate biomaterial‐driven vascularization in the porcine subcutaneous space. Additionally, we report the first use of cost‐effective fluorescent microspheres to quantify perfusion in the porcine subcutaneous space. We investigate the vascularization‐inducing efficacy of vascular endothelial growth factor (VEGF)‐delivering synthetic hydrogels based on 4‐arm poly(ethylene) glycol macromers with terminal maleimides (PEG‐4MAL). We compare three groups: a non‐degradable hydrogel with a VEGF‐releasing PEG‐4MAL gel coating (Core+VEGF gel); an uncoated, non‐degradable hydrogel (Core‐only); and naïve tissue. After 2 weeks, Core+VEGF gel has significantly higher tissue perfusion, blood vessel area, blood vessel density, and number of vessels compared to both Core‐only and naïve tissue. Furthermore, healthy vital signs during surgery and post‐procedure metrics demonstrate the safety of hydrogel delivery. We demonstrate that VEGF‐delivering synthetic hydrogels induce robust vascularization and perfusion in the porcine subcutaneous space.
“…Another minimally invasive and easily accessible area of islet transplantation is the subcutaneous space. Although subcutaneous islet transplant studies commonly involve the study of euglycemia restoration following diabetes induction, this method of transplantation has also been utilized in intravital microscopy studies involving photoacoustic imaging due to proximity to surface ( 24 ). However, to date, this method of imaging has only been used to study transplant revascularization in syngeneic recipient animals ( 24 ).…”
Section: Transplantation Sites For Fluorescent Imaging Purposesmentioning
confidence: 99%
“…Although subcutaneous islet transplant studies commonly involve the study of euglycemia restoration following diabetes induction, this method of transplantation has also been utilized in intravital microscopy studies involving photoacoustic imaging due to proximity to surface ( 24 ). However, to date, this method of imaging has only been used to study transplant revascularization in syngeneic recipient animals ( 24 ). The major drawback of using this site for islet transplantation is the relative avascularity of this environment compared to other transplantation sites discussed above.…”
Section: Transplantation Sites For Fluorescent Imaging Purposesmentioning
confidence: 99%
“…The major drawback of using this site for islet transplantation is the relative avascularity of this environment compared to other transplantation sites discussed above. Thus, an additional method must first be deployed to ensure engraftment, such as the induction of an immune response driving angiogenesis with insertion of a hollow nylon catheter ( 24 ) or through the use of a viability matrix with transplantation ( 23 ). Additionally, co-transplantation of islets and adipose-derived microvessels into the subcutaneous space may be employed to accelerate the establishment of a host-graft vascular network ( 79 ).…”
Section: Transplantation Sites For Fluorescent Imaging Purposesmentioning
Human islet transplantations into rodent models are an essential tool to aid in the development and testing of islet and cellular-based therapies for diabetes prevention and treatment. Through the ability to evaluate human islets in an in vivo setting, these studies allow for experimental approaches to answer questions surrounding normal and disease pathophysiology that cannot be answered using other in vitro and in vivo techniques alone. Intravital microscopy enables imaging of tissues in living organisms with dynamic temporal resolution and can be employed to measure biological processes in transplanted human islets revealing how experimental variables can influence engraftment, and transplant survival and function. A key consideration in experimental design for transplant imaging is the surgical placement site, which is guided by the presence of vasculature to aid in functional engraftment of the islets and promote their survival. Here, we review transplantation sites and mouse models used to study beta cell biology in vivo using intravital microscopy and we highlight fundamental observations made possible using this methodology.
“…Shi et al reported that PI can be used to track angiogenesis at a subcutaneous islet transplant site in a mouse model. 76 PI employed in this study may be used for tracking angiogenesis of transplanted islets. Figure 3 Trimodal imaging of transplanted pancreatic islets in scaffolds.…”
Although islet transplantation plays an effective and powerful role in the treatment of diabetes, a large amount of islet grafts are lost at an early stage due to instant bloodmediated inflammatory reactions, immune rejection, and β-cell toxicity resulting from immunosuppressive agents. Timely intervention based on the viability and function of the transplanted islets at an early stage is crucial. Various islet transplantation imaging techniques are available for monitoring the conditions of post-transplanted islets. Due to the development of various imaging modalities and the continuous study of contrast agents, noninvasive islet transplantation imaging in vivo has made great progress. The tracing and functional evaluation of transplanted islets in vivo have thus become possible. However, most studies on contrast agent and imaging modalities are limited to animal experiments, and long-term toxicity and stability need further evaluation. Accordingly, the clinical application of the current achievements still requires a large amount of effort. In this review, we discuss the contrast agents for MRI, SPECT/PET, BLI/FI, US, MPI, PAI, and multimodal imaging. We further summarize the advantages and limitations of various molecular imaging methods.
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