Niños y adolescentes: fármacos aprobados y su uso actual en la práctica clínica

Abstract

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of pancreatic β-cells and the progressive loss of endogenous insulin secretion. Although intensive insulin therapy and automated insulin delivery systems have improved the prognosis and quality of life of people with T1D (PwT1D), they do not precisely replicate the physiological regulation of blood glucose nor completely eliminate the risk of hypoglycemia. Pancreas and islet transplantation have demonstrated that replacing β-cell mass can restore endogenous insulin secretion and achieve exogenous insulin independence in selected patients. However, these procedures are limited by donor scarcity, monitoring complexity, and the requirement for chronic immunosuppression.

Regenerative medicine (RM) based on stem cells aims to overcome these limitations by generating pancreatic β-cells or islets from human pluripotent stem cells (hPSCs). These can be either human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs). Through directed differentiation protocols, hPSCs are sequentially guided from the endoderm toward pancreatic progenitors, the endocrine lineage, and finally mature β-cells. These mature cells are characterized by the expression of PDX1, NKX6.1, INS, C-peptide, MAFA, and UCN3, showing an appropriate functional response to glucose. This process has enabled the transition from insulin-producing cells to stem cell-derived pancreatic islet preparations (SC-islets), which are capable of partially replicating the organization and function of the native pancreatic islet.

Currently, several lines of research are underway: SC-islet transplantation with systemic immunosuppression; pancreatic progenitor cells with in vivo maturation; encapsulation and immunoprotective devices; alternative implantation sites; generation of autologous cells using iPSCs and chemically induced pluripotent stem cells; and gene editing aimed at creating cells resistant to both allogeneic rejection and autoimmunity recurrence.

The most significant clinical breakthrough corresponds to Zimislecel (VX-880), an allogeneic stem cell-derived islet therapy. In the FORWARD study, all PwT1D showed C-peptide secretion, and 10 out of 12 achieved insulin independence at one year. Although these results represent highly relevant evidence of feasibility, it must be considered that they were obtained in a small number of patients and required immunosuppression.

The current challenge is no longer solely to generate functional β-cells, but to protect them from autoimmunity and rejection, ensure their vascularization and survival, and thus demonstrate sustained safety and efficacy to achieve long-term insulin independence and T1D remission.