Emerging diabetes therapies: Bringing back the β-cells
Background: Stem cell therapies are finally coming of age as a viable alternative to pancreatic islet transplantation for the treatment of insulin-dependent diabetes. Several clinical trials using human embryonic stem cell (hESC)-derived β-like cells are currently underway, with encouraging prelimin...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-06-01
|
| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877822000461 |
| _version_ | 1818191673745735680 |
|---|---|
| author | G. Basile M.M.F. Qadir F. Mauvais-Jarvis A. Vetere V. Shoba A.E. Modell R.L. Pastori H.A. Russ B.K. Wagner J. Dominguez-Bendala |
| author_facet | G. Basile M.M.F. Qadir F. Mauvais-Jarvis A. Vetere V. Shoba A.E. Modell R.L. Pastori H.A. Russ B.K. Wagner J. Dominguez-Bendala |
| author_sort | G. Basile |
| collection | DOAJ |
| description | Background: Stem cell therapies are finally coming of age as a viable alternative to pancreatic islet transplantation for the treatment of insulin-dependent diabetes. Several clinical trials using human embryonic stem cell (hESC)-derived β-like cells are currently underway, with encouraging preliminary results. Remaining challenges notwithstanding, these strategies are widely expected to reduce our reliance on human isolated islets for transplantation procedures, making cell therapies available to millions of diabetic patients. At the same time, advances in our understanding of pancreatic cell plasticity and the molecular mechanisms behind β-cell replication and regeneration have spawned a multitude of translational efforts aimed at inducing β-cell replenishment in situ through pharmacological means, thus circumventing the need for transplantation. Scope of Review: We discuss here the current state of the art in hESC transplantation, as well as the parallel quest to discover agents capable of either preserving the residual mass of β-cells or inducing their proliferation, transdifferentiation or differentiation from progenitor cells. Major Conclusions: Stem cell-based replacement therapies in the mold of islet transplantation are already around the corner, but a permanent cure for type 1 diabetes will likely require the endogenous regeneration of β-cells aided by interventions to restore the immune balance. The promise of current research avenues and a strong pipeline of clinical trials designed to tackle these challenges bode well for the realization of this goal. |
| first_indexed | 2024-12-12T00:18:21Z |
| format | Article |
| id | doaj.art-844528a494564264821b9d6ab2bdef0b |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-12T00:18:21Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-844528a494564264821b9d6ab2bdef0b2022-12-22T00:44:48ZengElsevierMolecular Metabolism2212-87782022-06-0160101477Emerging diabetes therapies: Bringing back the β-cellsG. Basile0M.M.F. Qadir1F. Mauvais-Jarvis2A. Vetere3V. Shoba4A.E. Modell5R.L. Pastori6H.A. Russ7B.K. Wagner8J. Dominguez-Bendala9Joslin Diabetes Center, Harvard Medical School, Boston, MA, USATulane University School of Medicine, New Orleans, LA, USA; Southeast Louisiana Veterans Affairs Medical Center, New Orleans, LA, USATulane University School of Medicine, New Orleans, LA, USA; Southeast Louisiana Veterans Affairs Medical Center, New Orleans, LA, USABroad Institute, Cambridge, MA, USABroad Institute, Cambridge, MA, USABroad Institute, Cambridge, MA, USADiabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USABarbara Davis Center for Diabetes, Colorado University Anschutz Medical Campus, Aurora, CO, USA; Corresponding author. Barbara Davis Center for Diabetes, Colorado University Anschutz Medical Campus. 1775 Aurora Court, Aurora, CO, 80045, USA.Broad Institute, Cambridge, MA, USA; Corresponding author. Chemical Biology and Therapeutics Science Program, Broad Institute. 415 Main Street, Cambridge, MA, 02142, USA.Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA; Corresponding author. Diabetes Research Institute, University of Miami Miller School of Medicine, 1450 NW 10th Ave, Miami, FL, 33136, USA.Background: Stem cell therapies are finally coming of age as a viable alternative to pancreatic islet transplantation for the treatment of insulin-dependent diabetes. Several clinical trials using human embryonic stem cell (hESC)-derived β-like cells are currently underway, with encouraging preliminary results. Remaining challenges notwithstanding, these strategies are widely expected to reduce our reliance on human isolated islets for transplantation procedures, making cell therapies available to millions of diabetic patients. At the same time, advances in our understanding of pancreatic cell plasticity and the molecular mechanisms behind β-cell replication and regeneration have spawned a multitude of translational efforts aimed at inducing β-cell replenishment in situ through pharmacological means, thus circumventing the need for transplantation. Scope of Review: We discuss here the current state of the art in hESC transplantation, as well as the parallel quest to discover agents capable of either preserving the residual mass of β-cells or inducing their proliferation, transdifferentiation or differentiation from progenitor cells. Major Conclusions: Stem cell-based replacement therapies in the mold of islet transplantation are already around the corner, but a permanent cure for type 1 diabetes will likely require the endogenous regeneration of β-cells aided by interventions to restore the immune balance. The promise of current research avenues and a strong pipeline of clinical trials designed to tackle these challenges bode well for the realization of this goal.http://www.sciencedirect.com/science/article/pii/S2212877822000461Islet regenerationBeta cell proliferationPancreatic progenitor cellsHuman embryonic stem cell transplantation |
| spellingShingle | G. Basile M.M.F. Qadir F. Mauvais-Jarvis A. Vetere V. Shoba A.E. Modell R.L. Pastori H.A. Russ B.K. Wagner J. Dominguez-Bendala Emerging diabetes therapies: Bringing back the β-cells Molecular Metabolism Islet regeneration Beta cell proliferation Pancreatic progenitor cells Human embryonic stem cell transplantation |
| title | Emerging diabetes therapies: Bringing back the β-cells |
| title_full | Emerging diabetes therapies: Bringing back the β-cells |
| title_fullStr | Emerging diabetes therapies: Bringing back the β-cells |
| title_full_unstemmed | Emerging diabetes therapies: Bringing back the β-cells |
| title_short | Emerging diabetes therapies: Bringing back the β-cells |
| title_sort | emerging diabetes therapies bringing back the β cells |
| topic | Islet regeneration Beta cell proliferation Pancreatic progenitor cells Human embryonic stem cell transplantation |
| url | http://www.sciencedirect.com/science/article/pii/S2212877822000461 |
| work_keys_str_mv | AT gbasile emergingdiabetestherapiesbringingbackthebcells AT mmfqadir emergingdiabetestherapiesbringingbackthebcells AT fmauvaisjarvis emergingdiabetestherapiesbringingbackthebcells AT avetere emergingdiabetestherapiesbringingbackthebcells AT vshoba emergingdiabetestherapiesbringingbackthebcells AT aemodell emergingdiabetestherapiesbringingbackthebcells AT rlpastori emergingdiabetestherapiesbringingbackthebcells AT haruss emergingdiabetestherapiesbringingbackthebcells AT bkwagner emergingdiabetestherapiesbringingbackthebcells AT jdominguezbendala emergingdiabetestherapiesbringingbackthebcells |