The potential of stem cells
Stem cell and regenerative medicine technologies have the potential to cure diabetes, although we are certainly far from such a cure. Studies on rodents indicate that curative stem cell therapy of diabetes is possible, but experimental human trials applying non-myeloablative autologous hematopoietic stem cell transplantation or autologous umbilical cord blood infusions to patients with type 1 diabetes show mixed results. There have been some noteworthy recent studies on stem cell educator therapy and the transplantation of human beta cells containing a bioreactor to a patient with type 1 diabetes without the need for immunosuppression.
Profil and stem cell research
Profil Germany has a positive attitude to approaches to diabetes therapy based on stem cells and regenerative medicine provided that they meet the highest ethical standards and have the clear potential to overcome the limitations inherent in current insulin therapies. The latter include: under-insulinization of the liver and pancreas accompanied by over-insulinization of peripheral tissues; impaired glucagon suppression by the beta cells leading to glycemic volatility; and an imperfect match of basal and meal-related insulin requirements. Moreover, with current therapies, the natural pulsatility of insulin exposure is not restored so there is no de facto cure of diabetes. On the other hand, the relative success of recent insulin therapies has set high standards and made any therapy with significant negative side effects, such as long-term immunosuppression, unacceptable.
Profil Germany have been involved in various pharmaceutical and treatment development projects that focused on patients’ endogenous repair potential. Drugs that protect beta cells from death and/or stimulate endogenous beta cell regeneration could greatly improve the quality of life and clinical outcome for people with diabetes. Although there may be some potential for re-establishing endogenous beta cell function, even in older adults with type 1 diabetes, innovations primarily aim at the extension and intensification of the honeymoon phase at the beginning of type 1 diabetes. As functional beta cell depletion is already advanced in prediabetes and early type 2 diabetes, a meaningful use of beta cell protective drugs will depend on the co-development of powerful tools that enable the identification of people at high risk for diabetes far before signs of glycemic deterioration become detectable. Clinical trials should stratify patients based on the slope of the beta-cell loss of function time curve and curative effects should only be claimed if improved islet function persists after drug washout. Incretin-related compounds, SerpinB1 and NMDA-type glutamate receptor antagonists are candidates currently under investigation for their impact on human beta cell protection and islet regeneration.
At the same time, we see a high potential of exploring extrinsic repair strategies including the processing of autologous cell preparations and engineered tissues for the treatment of musculoskeletal conditions (e.g., tissue intermediates bridging the time until insertion of implants) and diabetic foot ulcers aiming to maintain patients’ mobility. Any ambitions to reconstruct beta cell function through beta cell replacement and/or stimulation of beta cell regeneration and neogenesis should be guided by the objective to fully reconstruct the islet architecture to build up the proper synthesis and processing of (pre-)pro-insulin, the highly regulated secretion of both insulin and glucagon, and the adaptive plasticity of beta cell function.