Stem cell therapy for endocrine and metabolic disorders

Abstract

Stem cell therapy is a highly promising avenue in regenerative medicine. In the domain of endocrine and metabolic diseases, it has shown therapeutic potential for conditions like hypothyroidism, hypopituitarism, primary adrenal insufficiency, osteoporosis, and diabetes and its complications. This treatment modality leverages the unique self-renewal and differentiation capabilities of stem cells into specific cell types, aiming to restore damaged tissue function and alleviate symptoms of hormonal imbalances, thus offering an alternative to long-term pharmacological treatments that often yield suboptimal results. Currently, research on the aforementioned diseases primarily concentrates on pluripotent and mesenchymal stem cells. Pluripotent stem cells primarily exert their therapeutic effects through cell replacement, making them the preferred choice for functional substitution of damaged cells in conditions like type 1 diabetes, hypothyroidism, hypopituitarism, and adrenal insufficiency. Conversely, mesenchymal stem cells offer distinct advantages via multifaceted mechanisms, such as anti-inflammatory, immune-regulating, and anti-apoptotic mechanisms, making them applicable to diseases rooted in inflammatory responses and immunoregulatory disturbances, encompassing autoimmune thyroiditis, primary adrenal insufficiency, osteoporosis, and diabetes and its complications. Nevertheless, stem cell therapy overall remains in early developmental stages, and its long-term safety and efficacy require further verification. For pluripotent stem cells, unresolved issues persist, including post-transplantation immune rejection, oncogenic potential, and ethical concerns. For mesenchymal stem cells, clinical benefit has been predominantly observed in early-stage patients with diabetes, and the optimal sources for distinct disease entities warrant further investigation. This review provides a comprehensive overview of the current therapeutic potential of stem cells in endocrine and metabolic diseases, the indications for various stem cell types, the challenges faced in their clinical translation, and the corresponding countermeasures.

Keywords: Stem cell therapy; Diabetes; Hypothyroidism; Hypopituitarism; Primary adrenal insufficiency; Osteoporosis

Core Tip: This review provides the first systematic comparison of pluripotent and mesenchymal stem cell strategies across major endocrine and metabolic disorders, diabetes, hypothyroidism, hypopituitarism, adrenal insufficiency, and osteoporosis. We establish a clear functional framework: Pluripotent stem cells-mediated cell replacement is applicable to diseases characterized by irreversible cell loss, whereas mesenchymal stem cell-mediated anti-inflammatory and immunomodulatory actions are applicable to inflammation- or immune-driven conditions. We also identify translational barriers and propose actionable solutions, offering a roadmap from proof-of-concept toward clinical practice.