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Islet Isolation from Pancreatitis Pancreas for Islet Autotransplantation

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Islets of Langerhans

Abstract

For patients suffering from intractable chronic pancreatitis, surgical removal of the pancreas may be recommended. While pancreatectomy has the potential to alleviate suffering and prolong life, the induction of iatrogenic diabetes, through the loss of insulin-producing islet cells, becomes an immediate threat to the postoperative patient. Since the procedure was first performed in 1977 at the University of Minnesota, autologous islet transplantation has become the best treatment option to restore a patient’s ability to endogenously regulate their blood sugar. Autologous islet isolation starts with a specific procurement and packaging of the pancreas, which is then transported to a specialized clean-room facility. The pancreas is distended with tissue dissociation enzymes that digest the extracellular matrix of the pancreas, freeing the embedded cells, which are combined into a single tube. If necessary, this tissue is purified by density gradient and the islets transferred to a transplant bag for intraportal infusion back into the patient. The most critical factor for a positive metabolic outcome from this procedure is the islet mass transplanted, making total isolation yield of particular concern. While the pancreas contains an abundance of islets, even the best isolation techniques capture only half of these. Furthermore, patient-donor characteristics and tissue conditions, like fibrosis and cell atrophy, can further diminish islet yields. Our goal at the University of Minnesota has been to research the underlying factors that influence islet yield and viability and to propose specific procedures designed to optimize isolation success regardless of tissue condition. The purpose of this review is to describe our basic protocol as well as to highlight our system of flexible techniques that can be adapted based on an ongoing evaluation of each individual pancreas and the procedural progress itself.

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Abbreviations

ATGS:

Analytical test gradient system

ATP:

Adenosine triphosphate

cGMP:

Current good manufacturing practices

CIT:

Clinical islet transplantation

CP:

Chronic pancreatitis

ECM:

Extracellular matrix

FDA:

Fluorescein diacetate

HBSS:

Hanks balanced salt solution

HSA:

Human serum albumin

HTK:

Histidine-tryptophan-ketoglutarate

IAT:

Islet autotransplantation

IEQ:

Islet equivalents

NEM:

New enzyme mixture

PI:

Propidium iodide

TLM:

Two-layer method

TP:

Total pancreatectomy

TP/IAT:

Total pancreatectomy and islet autotransplantation

UW:

University of Wisconsin (solution)

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Acknowledgments

The authors would like to thank Josh Wilhelm, Muhamad Abdulla, Mukesh Tiwari, Tom Gilmore, and Jeff Ansite.

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Authors and Affiliations

  1. Department of Surgery, Schulze Diabetes Institute, University of Minnesota, Harvard Street, 55455, Minneapolis, MN, USA

    Gopalakrishnan Loganathan, Amber Lockridge, Sajjad M. Soltani, Joshua J. Wilhelm, Gregory J. Beilman, Bernhard J. Hering & David E. R. Sutherland

  2. Islet Cell Laboratory, Cardiovascular Innovation Institute, Department of Surgery, University of Louisville, Louisville, KY, USA

    A. N. Balamurugan

Authors
  1. A. N. Balamurugan
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  2. Gopalakrishnan Loganathan
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  3. Amber Lockridge
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  4. Sajjad M. Soltani
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  5. Joshua J. Wilhelm
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  6. Gregory J. Beilman
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  7. Bernhard J. Hering
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  8. David E. R. Sutherland
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Corresponding author

Correspondence to A. N. Balamurugan .

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Editors and Affiliations

  1. Department of Clinical Sciences and Education, Sodersjukhuset, Karolinska Institutet, Stockholm, Sweden

    Md. Shahidul Islam

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Balamurugan, A.N. et al. (2015). Islet Isolation from Pancreatitis Pancreas for Islet Autotransplantation. In: Islam, M. (eds) Islets of Langerhans. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6686-0_48

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