Clinical Prospect of Mesenchymal Stromal/Stem Cell-Derived Extracellular Vesicles in Kidney Disease: Challenges and the Way Forward

Abstract

Kidney disease is a growing public health problem worldwide, including both acute and chronic forms. Existing therapies for kidney disease target various pathogenic mechanisms; however, these therapies only slow down the progression of the disease rather than offering a cure. One of the potential and emerging approaches for the treatment of kidney disease is mesenchymal stromal/stem cell (MSC) therapy, shown to have beneficial effects in preclinical studies. In addition, extracellular vesicles (EVs) released by MSCs became a potent cell-free therapy option in various preclinical models of kidney disease due to their regenerative, anti-inflammatory, and immunomodulatory properties. However, there are scarce clinical data available regarding the use of MSC-EVs in kidney pathologies. This review article provides an outline of the renoprotective effects of MSC-EVs in different preclinical models of kidney disease. It offers a comprehensive analysis of possible mechanisms of action of MSC-EVs with an emphasis on kidney disease. Finally, on the journey toward the implementation of MSC-EVs into clinical practice, we highlight the need to establish standardized methods for the characterization of an EV-based product and investigate the adequate dosing, safety, and efficacy of MSC-EVs application, as well as the development of suitable potency assays.

A quantitative review of nanotechnology‐based therapeutics for kidney diseases

“…Furthermore, EVs can be engineered post-isolation to carry exogenous chemicals and biomolecules (Tang et al, 2022). Across the EV landscape, those derived from mesenchymal stem cells (MSCs) have been manipulated to encapsulate therapeutic microRNAs, mRNAs, and proteins and are prominently used in the treatment of renal diseases such as AKI, diabetic kidney disease, and renal fibrosis (Ceccotti et al, 2023;Kosanovic et al, 2023;Tang et al, 2022).…”

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery

“…The intracellular membrane is not involved during the secretion of microvesicles, and thus the membrane composition closely mirrors that of parent cells, a key difference from exosomes, which are heavily enriched in phosphatidylserine [ 4 ]. Although several other types of EVs released from plasma membranes have been discovered, such as migrasomes, ciliary ectosomes, secreted midbody remnants, exophers, etc., they have recently been classified into two major categories: exosomes (originating from the endosomal compartment) and ectosomes (originating from the plasma membrane) [ 10 ]. Recently, several mechanisms have been identified to regulate the biogenesis of EVs, thereby facilitating the sorting of protein and RNA cargo to generate EVs with a precise biochemical composition [ 11 , 12 ].…”

“…Exosomes’ protein topology is the same as that of the releasing cell plasma membrane due to fusion of MVBs with plasma membrane, whereas the protein topology of microvesicles is heterogenous due to the direct budding off-plasma membrane [ 4 ]. Because there are no specific markers that differentiate between exosomes and microvesicles, investigating these two groups individually remains challenging [ 10 ]. The content of EV proteins ranges from general EV markers, subdivided into exosome markers (tetraspanins (CD9, CD63, CD81, and CD82), syntenin-1, TSG101, and Alix) and microvesicle markers (glycoprotein 1b, actinin-4, heat shock protein (HSP) 90B1, and myosin light chain) to post-translational protein modifications that specifically reflect vesicle localization, cellular origin (tissue-specific proteins), and secretion machinery [ 13 , 14 ].…”

A highly sensitive and specific Homo1‐based real‐time qPCR method for quantification of human umbilical cord mesenchymal stem cells in rats

“…In recent years, mesenchymal stem cells (MSCs) have been widely used in regenerative medicine for the ability of the multi-lineage differentiation, self-renewal, and low immunogenicity. After initially secured conditional application in graft-versus-host disease, osteogenesis imperfecta, and lysosomal storage diseases, MSCs and extracellular vesicles gradually play a role in the treatment of liver and lung injury, [1][2][3] arthritis, [4] and many refractory diseases, such as acute renal injury, [5][6][7] diabetes, [8] and diabetic complications. [9][10][11] Compared with MSCs derived from other sources, human umbilical cord-derived MSCs (UC-MSCs) have the characteristics of easier access in vitro, higher proliferation capacity, less cell-based aging, and no ethical concerns.…”