Oxygenation of islets and its role in transplantation

Lau, Joey; Henriksnäs, Johanna; Svensson, Johanna; Carlsson, Per‐Ola

doi:10.1097/mot.0b013e32833239ff

Cited by 63 publications

(62 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many investigators agree that the liver may not be the optimal site for islet survival or function and that inadequate oxygen supply may be an issue. [4][5][6][7] Reasons for why the liver may not represent the optimal site include the following:…”

Section: Review Articlementioning

confidence: 99%

Intraportal Islet Oxygenation

Suszynski

Avgoustiniatos

Papas

2014

J Diabetes Sci Technol

View full text Add to dashboard Cite

Islet transplantation (IT) is a promising therapy for the treatment of diabetes. The large number of islets required to achieve insulin independence limit its cost-effectiveness and the number of patients who can be treated. It is believed that >50% of islets are lost in the immediate post-IT period. Poor oxygenation in the early post-IT period is recognized as a possible reason for islet loss and dysfunction but has not been extensively studied. Several key variables affect oxygenation in this setting, including (1) local oxygen partial pressure (pO 2 ), (2) islet oxygen consumption, (3) islet size (diameter, D), and (4) presence or absence of thrombosis on the islet surface. We discuss implications of oxygen-limiting conditions on intraportal islet viability and function. Of the 4 key variables, the islet size appears to be the most important determinant of the anoxic and nonfunctional islet volume fractions. Similarly, the effect of thrombus formation on the islet surface may be substantial. At the University of Minnesota, average size distribution data from clinical alloislet preparations (n = 10) indicate that >150-µm D islets account for only ~30% of the total islet number, but >85% of the total islet volume. This suggests that improved oxygen supply to the islets may have a profound impact on islet survivability and function since most of the β-cell volume is within large islets which are most susceptible to oxygen-limiting conditions. The assumption that the liver is a suitable islet transplant site from the standpoint of oxygenation should be reconsidered.

show abstract

Section: Review Articlementioning

confidence: 99%

Intraportal Islet Oxygenation

Suszynski

Avgoustiniatos

Papas

2014

J Diabetes Sci Technol

View full text Add to dashboard Cite

show abstract

“…However, most reports on the effect of hypoxia on construct function are limited to in vitro settings 22,[24][25][26][27] ; in vivo evaluation of hypoxia is currently performed through indirect methods postexplantation. 15,16,28 We are therefore pursuing the development of a noninvasive method of monitoring dissolved oxygen concentration (DO) in a tissue-engineered pancreatic construct using 19 F nuclear magnetic resonance (NMR) spectroscopy, with perfluorocarbons (PFCs) as oxygen concentration markers. The principle behind this method is the linear relationship between the inverse spin lattice relaxation time of the fluorine resonances from PFCs and oxygen tension.…”

mentioning

confidence: 99%

“…7,9,14 The problem of limited construct oxygenation may be exacerbated by the low oxygen at the implantation site, and, in many cases, the absence of vascularization around these implants. 7,15,16 Currently, assessment of the in vivo function of a pancreatic construct relies on measurements of blood glucose and insulin or C-peptide levels during oral glucose challenges. 17 A direct evaluation of the physiological state of a construct can only be done at the experimental end-point; therefore, to obtain information on the dynamic changes occurring in vivo, animals need to be euthanized and constructs retrieved at various time points.…”

mentioning

confidence: 99%

In Vivo Noninvasive Monitoring of Dissolved Oxygen Concentration Within an Implanted Tissue-Engineered Pancreatic Construct

Goh

Sambanis

2011

Tissue Engineering Part C: Methods

View full text Add to dashboard Cite

The function of an implanted tissue-engineered pancreatic construct is influenced by many in vivo factors; however, assessing its function is based primarily on end physiologic effects. As oxygen significantly affects cell function, we established a dual perfluorocarbon method that utilizes 19 F nuclear magnetic resonance spectroscopy, with perfluorocarbons as oxygen concentration markers, to noninvasively monitor dissolved oxygen concentration (DO) in bTC-tet cell-containing alginate beads and at the implantation milieu. Beads were implanted in the peritoneal cavity of normal and streptozotocin-induced diabetic mice. Using this method, the feasibility of acquiring real-time in vivo DO measurements was demonstrated. Results showed that the mouse peritoneal environment is hypoxic and the DO is further reduced when bTC-tet cell constructs were implanted. The DO within cell-containing beads decreased considerably over time and could be correlated with the relative changes in the number of viable encapsulated cells. The reduction of construct DO due to the metabolic activity of the bTC-tet cells was also compatible with the implant therapeutic function, as observed in the reversal of hyperglycemia in diabetic mice. The importance of these findings in assessing implant functionality and host animal physiology is discussed.

show abstract

“…Macroencapsulation devices hold the possibility for graft recovery, which is advantageous from a safety point of view, in particular in trials with stem cell–derived cells. However, such a system also aggravates problems with nutrient supply to the transplanted tissue, with hypoxia‐related functional impairment and cell death in the clustered highly metabolically active islet tissue 2, 3. To solve this matter, the βAir device with an incorporated refillable oxygen tank was developed and successfully tested in small and large animal models 4, 5, 6.…”

Section: Introductionmentioning

confidence: 99%

Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus

Carlsson

Espes

Sedigh

et al. 2018

American Journal of Transplantation

Self Cite

153

131

View full text Add to dashboard Cite

Macroencapsulation devices provide the dual possibility of immunoprotecting transplanted cells while also being retrievable, the latter bearing importance for safety in future trials with stem cell–derived cells. However, macroencapsulation entails a problem with oxygen supply to the encapsulated cells. The βAir device solves this with an incorporated refillable oxygen tank. This phase 1 study evaluated the safety and efficacy of implanting the βAir device containing allogeneic human pancreatic islets into patients with type 1 diabetes. Four patients were transplanted with 1‐2 βAir devices, each containing 155 000‐180 000 islet equivalents (ie, 1800‐4600 islet equivalents per kg body weight), and monitored for 3‐6 months, followed by the recovery of devices. Implantation of the βAir device was safe and successfully prevented immunization and rejection of the transplanted tissue. However, although beta cells survived in the device, only minute levels of circulating C‐peptide were observed with no impact on metabolic control. Fibrotic tissue with immune cells was formed in capsule surroundings. Recovered devices displayed a blunted glucose‐stimulated insulin response, and amyloid formation in the endocrine tissue. We conclude that the βAir device is safe and can support survival of allogeneic islets for several months, although the function of the transplanted cells was limited (Clinicaltrials.gov: NCT02064309).

show abstract

Oxygenation of islets and its role in transplantation

Cited by 63 publications

References 47 publications

Intraportal Islet Oxygenation

Intraportal Islet Oxygenation

In Vivo Noninvasive Monitoring of Dissolved Oxygen Concentration Within an Implanted Tissue-Engineered Pancreatic Construct

Transplantation of macroencapsulated human islets within the bioartificial pancreas βAir to patients with type 1 diabetes mellitus

Contact Info

Product

Resources

About