Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes

Aaron A. Stock, Vita Manzoli, Teresa De Toni, Maria M. Abreu, Yeh Chuin Poh, Lillian Ye, Adam Roose, Felicia W. Pagliuca, Chris Thanos, Camillo Ricordi, Alice A. Tomei

Research output: Contribution to journalArticle

Abstract

The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients. Transplantation of conformal-coated islets into a confined well-vascularized site allows long-term diabetes reversal in fully MHC-mismatched diabetic mice without immunosuppression. Here, we demonstrated that human SC islets reaggregated from cryopreserved cells display glucose-stimulated insulin secretion in vitro. Importantly, we showed that conformally coated SC islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. Overall, these results provide support for further evaluation of safety and efficacy of conformal-coated SC islets in larger species. Scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Islet encapsulation may eliminate the need for chronic immunosuppression. Conformal coating seeks to overcome limitations of traditional microencapsulation. Transplantation of conformal-coated stem cell-derived islets might extend the applicability of islet transplantation to a larger cohort of patients.

Original languageEnglish (US)
Pages (from-to)91-104
Number of pages14
JournalStem Cell Reports
Volume14
Issue number1
DOIs
StatePublished - Jan 14 2020

Fingerprint

Medical problems
Stem cells
Type 1 Diabetes Mellitus
Islets of Langerhans
Islets of Langerhans Transplantation
Stem Cells
Coatings
Immunosuppression
Stem Cell Transplantation
Transplantation
Tissue Donors
Insulin
Drug Compounding
Inbred NOD Mouse
Microencapsulation
Adipose Tissue
Encapsulation
Safety
Glucose
Fats

Keywords

  • alginate
  • conformal coating
  • encapsulation
  • insulin
  • islet transplantation
  • polyethylene glycol
  • stem cell-derived islets
  • thiol-ene click chemistry
  • Type 1 Diabetes
  • β cells

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Cite this

Stock, A. A., Manzoli, V., De Toni, T., Abreu, M. M., Poh, Y. C., Ye, L., ... Tomei, A. A. (2020). Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes. Stem Cell Reports, 14(1), 91-104. https://doi.org/10.1016/j.stemcr.2019.11.004

Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes. / Stock, Aaron A.; Manzoli, Vita; De Toni, Teresa; Abreu, Maria M.; Poh, Yeh Chuin; Ye, Lillian; Roose, Adam; Pagliuca, Felicia W.; Thanos, Chris; Ricordi, Camillo; Tomei, Alice A.

In: Stem Cell Reports, Vol. 14, No. 1, 14.01.2020, p. 91-104.

Research output: Contribution to journalArticle

Stock, AA, Manzoli, V, De Toni, T, Abreu, MM, Poh, YC, Ye, L, Roose, A, Pagliuca, FW, Thanos, C, Ricordi, C & Tomei, AA 2020, 'Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes', Stem Cell Reports, vol. 14, no. 1, pp. 91-104. https://doi.org/10.1016/j.stemcr.2019.11.004
Stock, Aaron A. ; Manzoli, Vita ; De Toni, Teresa ; Abreu, Maria M. ; Poh, Yeh Chuin ; Ye, Lillian ; Roose, Adam ; Pagliuca, Felicia W. ; Thanos, Chris ; Ricordi, Camillo ; Tomei, Alice A. / Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes. In: Stem Cell Reports. 2020 ; Vol. 14, No. 1. pp. 91-104.
@article{eaa8a7d73b734d798b161d96681bee2d,
title = "Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes",
abstract = "The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients. Transplantation of conformal-coated islets into a confined well-vascularized site allows long-term diabetes reversal in fully MHC-mismatched diabetic mice without immunosuppression. Here, we demonstrated that human SC islets reaggregated from cryopreserved cells display glucose-stimulated insulin secretion in vitro. Importantly, we showed that conformally coated SC islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. Overall, these results provide support for further evaluation of safety and efficacy of conformal-coated SC islets in larger species. Scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Islet encapsulation may eliminate the need for chronic immunosuppression. Conformal coating seeks to overcome limitations of traditional microencapsulation. Transplantation of conformal-coated stem cell-derived islets might extend the applicability of islet transplantation to a larger cohort of patients.",
keywords = "alginate, conformal coating, encapsulation, insulin, islet transplantation, polyethylene glycol, stem cell-derived islets, thiol-ene click chemistry, Type 1 Diabetes, β cells",
author = "Stock, {Aaron A.} and Vita Manzoli and {De Toni}, Teresa and Abreu, {Maria M.} and Poh, {Yeh Chuin} and Lillian Ye and Adam Roose and Pagliuca, {Felicia W.} and Chris Thanos and Camillo Ricordi and Tomei, {Alice A.}",
year = "2020",
month = "1",
day = "14",
doi = "10.1016/j.stemcr.2019.11.004",
language = "English (US)",
volume = "14",
pages = "91--104",
journal = "Stem Cell Reports",
issn = "2213-6711",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - Conformal Coating of Stem Cell-Derived Islets for β Cell Replacement in Type 1 Diabetes

AU - Stock, Aaron A.

AU - Manzoli, Vita

AU - De Toni, Teresa

AU - Abreu, Maria M.

AU - Poh, Yeh Chuin

AU - Ye, Lillian

AU - Roose, Adam

AU - Pagliuca, Felicia W.

AU - Thanos, Chris

AU - Ricordi, Camillo

AU - Tomei, Alice A.

PY - 2020/1/14

Y1 - 2020/1/14

N2 - The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients. Transplantation of conformal-coated islets into a confined well-vascularized site allows long-term diabetes reversal in fully MHC-mismatched diabetic mice without immunosuppression. Here, we demonstrated that human SC islets reaggregated from cryopreserved cells display glucose-stimulated insulin secretion in vitro. Importantly, we showed that conformally coated SC islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. Overall, these results provide support for further evaluation of safety and efficacy of conformal-coated SC islets in larger species. Scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Islet encapsulation may eliminate the need for chronic immunosuppression. Conformal coating seeks to overcome limitations of traditional microencapsulation. Transplantation of conformal-coated stem cell-derived islets might extend the applicability of islet transplantation to a larger cohort of patients.

AB - The scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Transplantation of encapsulated stem cell-derived islets (SC islets) might extend the applicability of islet transplantation to a larger cohort of patients. Transplantation of conformal-coated islets into a confined well-vascularized site allows long-term diabetes reversal in fully MHC-mismatched diabetic mice without immunosuppression. Here, we demonstrated that human SC islets reaggregated from cryopreserved cells display glucose-stimulated insulin secretion in vitro. Importantly, we showed that conformally coated SC islets displayed comparable in vitro function with unencapsulated SC islets, with conformal coating permitting physiological insulin secretion. Transplantation of SC islets into the gonadal fat pad of diabetic NOD-scid mice revealed that both unencapsulated and conformal-coated SC islets could reverse diabetes and maintain human-level euglycemia for more than 80 days. Overall, these results provide support for further evaluation of safety and efficacy of conformal-coated SC islets in larger species. Scarcity of donors and need for immunosuppression limit pancreatic islet transplantation to a few patients with labile type 1 diabetes. Islet encapsulation may eliminate the need for chronic immunosuppression. Conformal coating seeks to overcome limitations of traditional microencapsulation. Transplantation of conformal-coated stem cell-derived islets might extend the applicability of islet transplantation to a larger cohort of patients.

KW - alginate

KW - conformal coating

KW - encapsulation

KW - insulin

KW - islet transplantation

KW - polyethylene glycol

KW - stem cell-derived islets

KW - thiol-ene click chemistry

KW - Type 1 Diabetes

KW - β cells

UR - http://www.scopus.com/inward/record.url?scp=85077648474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85077648474&partnerID=8YFLogxK

U2 - 10.1016/j.stemcr.2019.11.004

DO - 10.1016/j.stemcr.2019.11.004

M3 - Article

C2 - 31839542

AN - SCOPUS:85077648474

VL - 14

SP - 91

EP - 104

JO - Stem Cell Reports

JF - Stem Cell Reports

SN - 2213-6711

IS - 1

ER -