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Prediction of Clinical Outcome in Islet Allotransplantation

¹ The Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Palermo, Italy
² Diabetes Research Institute, Miller School of Medicine, University of Miami, Miami, Florida

Address correspondence and reprint requests to Camillo Ricordi, MD, Diabetes Research Institute, Miller School of Medicine, University of Miami, 1450 NW 10 Ave., Miami, FL 33136 or Federico Bertuzzi, MD, ISMETT, via Tricomi 1, Palermo, Italy. E-mail: ricordi@miami.edu or fbertuzzi@ismett.edu

Abbreviations: IL, interleukin • MCP-1, monocyte chemoattractant protein-1 • OCR, oxygen consumption rate

The first 300 words of the full text of this article appear below.

	INTRODUCTION

 
Recent progresses in the pancreas’ enzymatic digestion process along with novel immunosuppression strategies have led to successful clinical trials of islet transplantation in humans. On the other hand, clinical outcome remains variable and unpredictable in centers with limited experience. The possibility of predicting in vivo islet graft function should allow the selection of preparations on the basis of their potential success, thus improving the overall results and making the processes more consistent and reproducible.

Graft function prediction is a work in progress. Initially, the best parameters representative of engrafted islet mass in recipients should be defined. Fasting C-peptide and exogenous insulin requirements are commonly used, although other methods for a more complete characterization of graft function (i.e., ß-score) have recently been described but not validated in a large number of patients. In addition, some of these data were shown to predict long-term graft function and might be used to establish whether recipients require further islet infusions.

Many pretransplant parameters representative of islet preparations and predictive for in vivo function have been proposed. C-peptide values as well as the exogenous insulin requirements of recipients were shown to be directly correlated with the number of transplanted islets, but there are many exceptions to this association. Other methods to define the quality of an islet preparation include analyses of islet morphology, cell composition, response to glucose, and viability and production of proinflammatory molecules. The most promising appear to be those that simultaneously analyze more than one aspect of islet physiology.

Islet transplantation has great potential for the normalization of the main parameters of glucose metabolism in diabetic patients. A sufficient number of islets can now be obtained from good quality pancreata more frequently than in the past, and diabetes can generally be reversed, normalizing A1C levels and eliminating severe hypoglycemic episodes (1. . . [Full Text of this Article]

	REPRESENTATIVE PARAMETERS OF ENGRAFTED ß-CELL MASS—

 

	IN VITRO PREDICTIVE PARAMETERS OF GRAFT FUNCTION: ISLET PREPARATION QUALITY

 
ß-Cell mass
Islet viability
Islet integrity
Islet preparation composition
Islet insulin secretion

	IN VITRO PREDICTIVE PARAMETERS OF GRAFT FUNCTION: ISLET PROINFLAMMATORY CONDITION—

 

	IN VIVO PREDICTIVE PARAMETERS OF GRAFT FUNCTION—

 

	PREDICTION OF CLINICAL OUTCOME IN ISLET ALLOTRANSPLANTATION: THE "INTEGRATED APPROACH"—

 

	PREDICTION OF CLINICAL OUTCOME IN ISLET ALLOTRANSPLANTATION: AN ON-GOING SCIENCE—

 

	CONCLUSIONS—

 

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