Alginate-microencapsulation of human stem cell-derived β cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression

Am J Transplant. 2019 Jul;19(7):1930-1940. doi: 10.1111/ajt.15308. Epub 2019 Mar 25.


Pancreatic β-cell replacement by islet transplantation for the treatment of type 1 diabetes (T1D) is currently limited by donor tissue scarcity and the requirement for lifelong immunosuppression. The advent of in vitro differentiation protocols for generating functional β-like cells from human pluripotent stem cells, also referred to as SC-β cells, could eliminate these obstacles. To avoid the need for immunosuppression, alginate-microencapsulation is widely investigated as a safe path to β-cell replacement. Nonetheless, inflammatory foreign body responses leading to pericapsular fibrotic overgrowth often causes microencapsulated islet-cell death and graft failure. Here we used a novel approach to evade the pericapsular fibrotic response to alginate-microencapsulated SC-β cells; an immunomodulatory chemokine, CXCL12, was incorporated into clinical grade sodium alginate to microencapsulate SC-β cells. CXCL12 enhanced glucose-stimulated insulin secretion activity of SC-β cells and induced expression of genes associated with β-cell function in vitro. SC-β cells co-encapsulated with CXCL12 showed enhanced insulin secretion in diabetic mice and accelerated the normalization of hyperglycemia. Additionally, SC-β cells co-encapsulated with CXCL12 evaded the pericapsular fibrotic response, resulting in long-term functional competence and glycemic correction (>150 days) without systemic immunosuppression in immunocompetent C57BL/6 mice. These findings lay the groundwork for further preclinical translation of this approach into large animal models of T1D.

Keywords: basic (laboratory) research/science; diabetes: type 1; endocrinology/diabetology; fibrosis; immune regulation; immunosuppression/immune modulation; insulin/C-peptide; islet transplantation; islets of Langerhans; translational research/science.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry*
  • Animals
  • Blood Glucose / metabolism
  • Chemokine CXCL12 / metabolism*
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / pathology
  • Diabetes Mellitus, Type 1 / therapy*
  • Female
  • Graft Survival*
  • Humans
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / metabolism
  • Islets of Langerhans Transplantation / methods*
  • Mice
  • Mice, Inbred C57BL
  • Stem Cells / cytology*
  • Stem Cells / metabolism


  • Alginates
  • Blood Glucose
  • Chemokine CXCL12
  • Insulin