Concise Review: Cell-Based Therapies and Other Non-Traditional Approaches for Type 1 Diabetes

Abstract

The evolution of Type 1 diabetes (T1D) therapy has been marked by consecutive shifts, from insulin replacement to immunosuppressive drugs and targeted biologics (following the understanding that T1D is an autoimmune disease), and to more disease‐specific or patient‐oriented approaches such as antigen‐specific and cell‐based therapies, with a goal to provide efficacy, safety, and long‐term protection. At the same time, another important paradigm shift from treatment of new onset T1D patients to prevention in high‐risk individuals has taken place, based on the hypothesis that therapeutic approaches deemed sufficiently safe may show better efficacy if applied early enough to maintain endogenous β cell function, a concept supported by many preclinical studies. This new strategy has been made possible by capitalizing on a variety of biomarkers that can more reliably estimate the risk and rate of progression of the disease. More advanced (“omic”‐based) biomarkers that also shed light on the underlying contributors of disease for each individual will be helpful to guide the choice of the most appropriate therapies, or combinations thereof. In this review, we present current efforts to stratify patients according to biomarkers and current alternatives to conventional drug‐based therapies for T1D, with a special emphasis on cell‐based therapies, their status in the clinic and potential for treatment and/or prevention. Stem Cells 2016;34:809–819

Nano‐curcumin safely prevents streptozotocin‐induced inflammation and apoptosis in pancreatic beta cells for effective management of Type 1 diabetes mellitus

“…Over the years, we have witnessed a plethora of developments in T1DM therapies that include insulin replacement, immunosuppression, antigen‐specific and cell‐based approaches. T1DM prevention in high‐risk individuals remains the highest priority where the goal is to maintain endogenous beta cell function (Creusot et al, ; Li et al, ). Therefore, protection of beta cells from cell death is considered as a new therapeutic target (Srimal and Dhawan, ; Ardestani and Maedler, ; Imai et al, ; Roy et al, ), where natural and safe anti‐inflammatory agents, such as curcumin (CUR)(Srimal and Dhawan, ; Castro et al, ), can perform better than some of the biological agents, such as canakinumab, a fully human anti‐IL‐1β monoclonal antibody (IgG‐1κ class), tested in trials with limited success (Cabrera et al, ).…”

Prospects of Advanced Therapy Medicinal Products–Based Therapies in Regenerative Dentistry: Current Status, Comparison with Global Trends in Medicine, and Future Perspectives

“…Nevertheless, concerns are emerging from the extensive use of hospital exemption at national levels, because it may restrain the submission of MA applications to the EMA. Although all the above-mentioned "short cuts" may be related to biased or imprecise results, they represent a primary source of prevailing paradigms paving the way for further experimental research and translation 65,66 .…”

Prediction and prevention of type 1 diabetes in children

“… (9–27). Another important aspect is to differentiate the children who maintain a sufficient beta-cell mass (which could benefit from treatments that improve beta-cell function and protect the remaining beta-cell mass), from children with a high degree of inflammatory and autoimmune phenomena against beta cells (which could benefit from a specific immunological intervention) (9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28). Another promising approach is to improve the knowledge on the so-called ‘trimolecular complex’ consisting of T-cell receptor, autoantigen and HLA class II; in fact, from this interaction beta cell autoantibodies are produced.…”

“…In other trials a monoclonal antibody that binds a specific peptide/HLA complex is used in order to block the activation of T lymphocytes. Finally, monoclonal antibodies against specific lymphocyte T (alpha or beta chain) receptors may be used to induce the depletion of autoreactive T lymphocytes (10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29, 30). The “INNODIA Project” (Translational approaches to disease modifying therapy of type 1 diabetes: an INNO vative approach towards understanding and arresting type 1 DIA betes) is a Consortium financed by the Horizon 2020 European Framework Program (31), which involves 26 academic institutions, 2 patient associations, 4 pharmaceutical industry partners (EFPIA) and small and medium size enterprise (SME).…”