Get Permission
Rev Diabet Stud, 2014, 11(1):84-101 DOI 10.1900/RDS.2014.11.84

Islet and Stem Cell Encapsulation for Clinical Transplantation

Rahul Krishnan1, Michael Alexander1, Lourdes Robles1, Clarence E. Foster 3rd1,2, Jonathan R.T. Lakey1,3

1Department of Surgery, University of California Irvine, Orange, CA 92868, USA
2Department of Transplantation, University of California Irvine, Orange, CA 92868, USA
3Biomedical Engineering, University of California Irvine, Irvine, CA 92697, USA
Address correspondence to: Jonathan R.T. Lakey, Director of Research and Clinical Islet Program, University of California Irvine, 333 City Blvd. West, Suite 1600, Orange, CA 92868, USA, e-mail:

Manuscript submitted June 19, 2013; resubmitted August 1, 2013; accepted August 9, 2013.

Keywords: type 1 diabetes, stem cell, encapsulation, tissue engineering, insulin-producing cell, transplantation


Over the last decade, improvements in islet isolation techniques have made islet transplantation an option for a certain subset of patients with long-standing diabetes. Although islet transplants have shown improved graft function, adequate function beyond the second year has not yet been demonstrated, and patients still require immunosuppression to prevent rejection. Since allogeneic islet transplants have experienced some success, the next step is to improve graft function while eliminating the need for systemic immunosuppressive therapy. Biomaterial encapsulation offers a strategy to avoid the need for toxic immunosuppression while increasing the chances of graft function and survival. Encapsulation entails coating cells or tissue in a semipermeable biocompatible material that allows for the passage of nutrients, oxygen, and hormones while blocking immune cells and regulatory substances from recognizing and destroying the cell, thus avoiding the need for systemic immunosuppressive therapy. Despite advances in encapsulation technology, these developments have not yet been meaningfully translated into clinical islet transplantation, for which several factors are to blame, including graft hypoxia, host inflammatory response, fibrosis, improper choice of biomaterial type, lack of standard guidelines, and post-transplantation device failure. Several new approaches, such as the use of porcine islets, stem cells, development of prevascularized implants, islet nanocoating, and multilayer encapsulation, continue to generate intense scientific interest in this rapidly expanding field. This review provides a comprehensive update on islet and stem cell encapsulation as a treatment modality in type 1 diabetes, including a historical outlook as well as current and future research avenues.

Fulltext: HTML , PDF (254KB)

This article has been cited by other articles:

Islet Microencapsulation: Strategies and Clinical Status in Diabetes

Omami M, McGarrigle JJ, Reedy M, Isa D, Ghani S, Marchese E, Bochenek MA, Longi M, Xing Y, Joshi I, Wang Y, Oberholzer J

Curr Diab Rep 2017. 17(7):47

Microencapsulation in Clinical Islet Xenotransplantation

Shimoda M, Matsumoto S

Methods Mol Biol 2017. 1479:335-345

Engineering Cell Surfaces with Polyelectrolyte Materials for Translational Applications

Zhang P, Bookstaver ML, Jewell CM

Polymers 2017. 9(2):40

A Synthetic Mammalian Therapeutic Gene Circuit for Sensing and Suppressing Inflammation

Smole A, Lainscek D, Bezeljak U, Horvat S, Jerala R

Mol Ther 2017. 25(1):102-119

Does exercise pose a challenge to glucoregulation after clinical islet transplantation?

Funk DR, Boule NG, Senior PA, Yardley JE

Appl Physiol Nutr Metab 2017. 42(1):1-7

Induction of Nestin Early Expression as a Hallmark for Mesenchymal Stem Cells Expression of PDX-1 as a Pre-disposing Factor for Their Conversion into Insulin Producing Cells

Martinez-Gamboa M, Cruz-Vega DE, Moreno-Cuevas J, Gonzalez-Garza MT

Int J Stem Cells 2017. 10(1):76-82

Smart biomaterials for cell encapsulation

Zhu H, Cao Z

RSC Smart Mat Tiss Engin 2017. 144-168

TGF-beta affinity-bound to a macroporous alginate scaffold generates local and peripheral immunotolerant responses and improves allocell transplantation

Orr S, Strominger I, Eremenko E, Vinogradov E, Ruvinov E, Monsonego A, Cohen S

Acta Biomater 2016. 45:196-209

CD133+ cells: How could they have an IMPACT?

Menasche P

J Thorac Cardiovasc Surg 2016. 152(6):1589-1591

Beta Cell Formation in vivo Through Cellular Networking, Integration and Processing (CNIP) in Wild Type Adult Mice

Doiron B, Hu W, DeFronzo RA

Curr Pharm Biotechnol 2016. 17(4):376-88

Progress and challenges for treating type 1 diabetes

Garyu JW, Meffre E, Cotsapas C, Herold KC

J Autoimmun 2016. 71:1-9

Progress and challenges of the bioartificial pancreas

Hwang PT, Shah DK, Garcia JA, Bae CY, Lim DJ, Huiszoon RC, Alexander GC, Jun HW

Nano Converg 2016. 3(1):28

Application of encapsulation technology in stem cell therapy

Hashemi M, Kalalinia F

Life Sci 2015. 143:139-146

Cell encapsulation: technical and clinical advances

Orive G, Santos E, Poncelet D, Hernandez RM, Pedraz JL, Wahlberg LU, De Vos P, Emerich D

Trends Pharmacol Sci 2015. 36(8):537-546

Impact of donor age and weaning status on pancreatic exocrine and endocrine tissue maturation in pigs

Krishnan R, Truong N, Gerges M, Stiewig M, Neel N, Ho-Nguyen K, Kummerfeld C, Alexander M, Spizzo T, Martin M, Foster CE 3rd, Monuki ES, Lakey JR

Xenotransplantation 2015. 22(5):356-367

Outpatient Management of Pediatric Type 1 Diabetes

Beck JK, Cogen FR

J Pediatr Pharmacol Ther 2015. 20(5):344-357

Osteochondritis dissecans of the lateral femoral condyle in a patient affected by osteogenesis imperfecta: a case report

Persiani P, Di Domenica M, Martini L, Ranaldi FM, Zambrano A, Celli M, Villani C

J Pediatr Orthop B 2015. 24(6):521-525

Immunogenicity of beta-cells for autologous transplantation in type 1 diabetes

Schuetz C, Markmann JF

Pharmacol Res 2015. 98:60-68

Transplantable bioartificial pancreas devices: current status and future prospects

Ludwig B, Ludwig S

Langenbecks Arch Surg 2015. 400(5):531-540

Overview of Cellular Transplantation in Diabetes Mellitus: Focus on the Metabolic Outcome

Luzi L, Benedini S, Caumo A, Terruzzi I

Adv Endocrinol 2015. 2015:967562