Kidney-Derived ECM Hydrogels as Cell Delivery Devices.

Abstract

Chronic kidney disease (CKD) represents a significant global health challenge, as emphasized by its increasing prevalence and limited treatment options. Stem cell-based therapies are promising alternatives for CKD treatment. In particular, adipose-derived mesenchymal stem cells (ASCs) have emerged as an attractive candidate cell source. However, challenges in optimizing stem cell delivery and survival upon implantation persist. The inclusion of stem cells in hydrogels addresses these challenges by providing mechanical support coupled to bioactive cues essential for kidney regeneration. In particular, hydrogels derived from a decellularized kidney extracellular matrix (dKECM) offer a biomimetic platform rich in native and important renal components. Herein, we investigate the performance of dKECM hydrogels with respect to the differentiation of ASCs toward kidney-specific phenotypes. First, dKECM hydrogels were characterized and compared with commercially available collagen I hydrogels, which are typically used for this therapeutic application. Subsequently, we evaluated the performance of encapsulated human ASCs and proximal tubular cells (HK-2 cell line), elucidating the impact of these hydrogels on their viability, metabolic activity, proliferation, morphology, and renal phenotype. Our findings highlight the superior potential of dKECM hydrogels in promoting a sustained cellular activity and phenotype , underscoring their promise for CKD therapy. This study provides valuable insights into the potency of decellularized-based hydrogels as cell delivery vehicles, offering promising avenues for CKD treatment and kidney regeneration.