ABSTRACT
Introduction
Type 1 diabetes (T1D) is a lifelong condition resulting from autoimmune destruction of insulin-producing β-cells. Islet or whole-pancreas transplantation is limited by the shortage of donors and need for chronic immune suppression. Novel strategies are needed to prevent β-cell loss and to rescue production of endogenous insulin.
Areas covered
This review covers the latest advances in cell-based therapies for the treatment and prevention of T1D. Topics include adoptive transfer of cells with increased immunoregulatory potential for β-cell protection, and β-cell replacement strategies such as generation of insulin-producing β-like cells from unlimited sources.
Expert opinion
Cell therapy provides an opportunity to prevent or reverse T1D. Adoptive transfer of autologous cells having enhanced immunomodulatory properties can suppress autoimmunity and preserve β-cells. Such therapies have been made possible by a combination of genome-editing techniques and transplantation of tolerogenic cells. In-vitro modified autologous hematopoietic stem cells and tolerogenic dendritic cells may protect endogenous and newly generated β-cells from a patient’s autoimmune response without hampering immune surveillance for infectious agents and malignant cellular transformations. However, methods to generate cells that meet quality and safety standards for clinical applications require further refinement.
Article Highlights
A definitive cure for T1D is centered around protecting β-cells from autoimmunity and on regenerating/replacing β-cells.
All approaches designed to stop β-cell disruption have failed, while transplantation of pancreas or pancreatic islets obtained from deceased donors cannot meet the growing demand.
Regulatory T cells, hematopoietic stem cells, and tolerogenic dendritic cells can be turned into islet-targeting immunoprotective tools in vitro, and adoptively transferred into patients with T1D to preserve residual β-cells and rescue β-cell function.
ESC- or iPSC-derived cells are an unlimited source of functionally active β-like cells that can be engineered to escape recipient’s alloimmune and autoimmune reactions.
Generating cells endowed with enhanced immunosuppressive properties and capable of immunoevasion holds great potential for β-cell immunopreservation and replacement in T1D cell therapies.
This box summarizes key points contained in the article.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer Disclosures
Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.