Transplanted Functional Islet Mass

Friberg, Andrew; Lundgren, Torbjörn; Malm, Helene; Felldin, Marie; Nilsson, Bo; Jenssen, Trond; Kyllönen, L.; Tufveson, Gunnar; Tibell, Annika; Korsgren, Olle

doi:10.1097/tp.0b013e3182455912

Cited by 22 publications

(9 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…All functional and viability analyses were performed according to standard protocols ( http://nordicislets.medscinet.com/en.aspx ). The day after islet isolation, quality analyses were performed using a dynamic glucose-stimulated insulin secretion (GSIS) perfusion test (Brandel, London, UK) ( Figure 2 ) on 20 handpicked islets to calculate the stimulation index (average of the high-glucose phase divided by the average of the low-glucose phase) 12 . Islet quality control in one isolation was performed using a modified protocol that mainly included a shortened perfusion period.…”

Section: Methodsmentioning

confidence: 99%

Calcium

et al. 2018

Self Cite

View full text Add to dashboard Cite

Background:Effective digestive enzymes are crucial for successful islet isolation. Supplemental proteases are essential because they synergize with collagenase for effective pancreatic digestion. The activity of these enzymes is critically dependent on the presence of Ca2+ ions at a concentration of 5–10 mM. The present study aimed to determine the Ca2+ concentration during human islet isolation and to ascertain whether the addition of supplementary Ca2+ is required to maintain an optimal Ca2+ concentration during the various phases of the islet isolation process.Methods:Human islets were isolated according to standard methods and isolation parameters. Islet quality control and the number of isolations fulfilling standard transplantation criteria were evaluated. Ca2+ was determined by using standard clinical chemistry routines. Islet isolation was performed with or without addition of supplementary Ca2+ to reach a Ca2+ of 5 mM.Results:Ca2+ concentration was markedly reduced in bicarbonate-based buffers, especially if additional bicarbonate was used to adjust the pH as recommended by the Clinical Islet Transplantation Consortium. A major reduction in Ca2+ concentration was also observed during pancreatic enzyme perfusion, digestion, and harvest. Additional Ca2+ supplementation of media used for dissolving the enzymes and during digestion, perfusion, and harvest was necessary in order to obtain the concentration recommended for optimal enzyme activity and efficient liberation of a large number of islets from the human pancreas.Conclusions:Ca2+ is to a large extent consumed during clinical islet isolation, and in the absence of supplementation, the concentration fell below that recommended for optimal enzyme activity. Ca2+ supplementation of the media used during human pancreas digestion is necessary to maintain the concentration recommended for optimal enzyme activity. Addition of Ca2+ to the enzyme blend has been implemented in the standard isolation protocols in the Nordic Network for Clinical Islet Transplantation.

show abstract

Section: Methodsmentioning

confidence: 99%

Calcium

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, to reduce islet loss through purification, no or minimal processing with density centrifugation is performed, and so islets are transplanted with varying amounts of exocrine tissue. This exocrine tissue may impact local inflammation and cell loss [23,24]. Alternatively, data suggest a potential benefit of cotransplantation of pancreatic duct cells which are a source of pancreatic ductal progenitor cells which may support islet neogenesis, as well as angiogenic proteins [25][26][27][28]29 in-vivo experience with observation of unexpected insulin independence in children receiving lowdose autologous islet transplants [30,31 && ].…”

Section: Autoisletsmentioning

confidence: 99%

Beta-cell replacement therapy

Dunn

Kirchner²,

Bellin

2015

Current Opinion in Organ Transplantation

View full text Add to dashboard Cite

Purpose of reviewThis article provides a summary of the current outcomes of b-cell replacement strategies, an algorithm for choosing a specific modality while highlighting associated advantages and disadvantages, and outlines remaining challenges and areas of active investigation in b-cell replacement therapy. Recent findingsThe most recent reports of islet cell allotransplantation have shown improvements over previous eras and now rival some outcomes of pancreas alone transplantation. Active areas of investigation are focused on improving techniques for islet isolation, graft monitoring, and managing challenges posed by the innate and alloimmune systems. SummaryPatients with insulin-dependent diabetes who continue to experience life threatening hypoglycemia despite maximal medical management can benefit from b-cell replacement. Emerging nontransplant technologies have not provided a physiologic euglycemic state to the extent offered by transplantation. Islet transplantation eliminates hypoglycemic episodes/unawareness, facilitates normalization of hemoglobin A1c (HbA1c), decreases microvascular disease progression, and improves quality of life for patients with problematic diabetes. Mid-and long-term outcomes of islet transplantation performed at expert centers approximate those of registry reports of solitary pancreas transplant, whereas the complication profile is quite favorable.

show abstract

“…Shapiro summarized results in at least six international islet transplant centers reporting similar high insulin independence rates at 5 years, suggesting parity of outcome of islet and pancreas-alone transplantation at 5 years in highly selected leading centers [32]. While the results of IAK transplantation appear to parallel the results of islet-alone transplantation at 3 years [33][34][35], longer term outcome data is clearly needed as the outcomes of PAK are still superior to PTA, and further robust studies are awaited to compare long term outcomes of IAK with PAK.…”

Section: Recent Outcomes Have Improved Substantially In Both Pancreasmentioning

confidence: 99%

Pancreas Versus Islets After a Successful Kidney Transplant

2014

View full text Add to dashboard Cite

The optimal endocrine transplant that should follow a successful kidney transplant in patients with type 1 diabetes is currently open to debate. Ideally, a combined kidney and pancreas transplant is carried out simultaneously from an optimal donor as there is clear immunological benefit. However, when a living donor kidney transplant occurs initially, either a pancreas after kidney or islet after kidney transplant may be considered. A pancreas after kidney transplant carries more surgical risk but provides more robust endocrine reserve compared to the alternative option of islet after kidney transplantation. Furthermore, islet transplantation is not universally available, requires specialized manufacturing facilities, and the costs associated with islet manufacture may not be reimbursable by healthcare. From a patient's perspective, however, islet after kidney transplantation is a highly attractive option to avoid further surgical risk and recovery. This paper discusses the merits and demerits of these alternative transplant options, and debates both competitive aspects and complementarity. We discuss current outcomes and ongoing clinical trials.

show abstract

Transplanted Functional Islet Mass

Abstract: The TFIM provides a straightforward and potent tool to guide the decision to use a specific islet preparation for clinical transplantation.

Cited by 22 publications

References 50 publications

Calcium

Calcium

Beta-cell replacement therapy

Pancreas Versus Islets After a Successful Kidney Transplant

Contact Info

Product

Resources

About