New perspectives on the treatment of diabetic nephropathy: Challenges and prospects of mesenchymal stem cell therapy

Abstract

Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes mellitus. Traditional treatment methods have certain limitations and it is difficult to effectively delay the disease progression. Mesenchymal stem cells (MSCs), owing to their potential for self-renewal, multidirectional differentiation, and immunomodulatory abilities, can regulate the renal immune microenvironment and repair damaged tissues, providing a new strategy for the treatment of DN. However, MSCs face problems such as immune rejection, cell inactivation, challenges in directed differentiation, insufficient homing ability, and low cell retention rate after delivery. These issues limit their clinical application in patients with DN. This review aims to propose optimization strategies targeting DN pathological features to improve MSC effectiveness and reduce their side effects. Specifically, it involves optimizing cell culture systems and cryopreservation protocols, along with pre-transplantation pharmacological conditioning to boost the functionality and viability of MSCs. Additionally, the exploration of synergistic drug-MSC combination therapies was carried out, taking advantage of diverse mechanisms of action to improve therapeutic outcomes. The integration of biomaterials and gene editing technologies to significantly enhance cell survival, target specificity, and tissue engraftment was also pursued. Concurrently, the determination of optimal therapeutic dosages and administration routes remained crucial. These multifaceted strategies not only provide a theoretical framework for overcoming existing technical limitations but also lay a robust foundation for accelerating the clinical translation of MSC-based therapies.