Urine-derived stem cells in neurological diseases: current state-of-the-art and future directions

Abstract

Stem cells have potential applications in the field of neurological diseases, as they allow for the development of new biological models. These models can improve our understanding of the underlying pathologies and facilitate the screening of new therapeutics in the context of precision medicine. Stem cells have also been applied in clinical tests to repair tissues and improve functional recovery. Nevertheless, although promising, commonly used stem cells display some limitations that curb the scope of their applications, such as the difficulty of obtention. In that regard, urine-derived cells can be reprogrammed into induced pluripotent stem cells (iPSCs). However, their obtaining can be challenging due to the low yield and complexity of the multi-phased and typically expensive differentiation protocols. As an alternative, urine-derived stem cells (UDSCs), included within the population of urine-derived cells, present a mesenchymal-like phenotype and have shown promising properties for similar purposes. Importantly, UDSCs have been differentiated into neuronal-like cells, auspicious for disease modeling, while overcoming some of the shortcomings presented by other stem cells for these purposes. Thus, this review assesses the current state and future perspectives regarding the potential of UDSCs in the ambit of neurological diseases, both for disease modeling and therapeutic applications.

Keywords: advanced therapies; exosomes; neurological diseases; neuronal differentiation; regenerative medicine; urine-derived stem cells.

Figure 1

Characterization and differentiation potential of UDSCs. UDSCs can be isolated from the urine of healthy subjects or patients of all ages and have a similar phenotype to mesenchymal stroma cells (MSC). UDSCs express MSC surface markers, pluripotent and embryonic stem cell markers. UDSCs evidence a certain degree of pluripotency and can be directly differentiated into cells of the three germ layers: neurons, hepatocytes-like cells, osteocytes, adipocytes, chondrocytes, cardiomyocytes, endothelial cells and skeletal myogenic cells, renal cells, podocytes and tubular epithelial cells. ESC, embryonic stem cell; PSC, pluripotent stem cell. Created with BioRender.com.

Figure 2

UDSCs-induced neuronal differentiation and brain disease applications. UDSCs isolated from the urine can be directly converted into neuron-like cells divided into different neuronal type depending on their specific markers (motor, glutamatergic, gabaergic or cholinergic). UDSCs-derived neurons may be employed in disease modeling approaches, to perform in vitro pharmacological tests, and for precision medicine. ChAT, Choline acetyltransferase; EVs, extracellular vesicles; GABA, gamma-aminobutyric acid; HB9 homeobox HB9; MAP2, microtubule-associated protein 2; NeuN, hexaribonucleotide binding protein-3; NFM, neurofilament marker; NF200, neurofilament 200; NPCs, neural progenitor cells; PSA-Ncam (polysialylated neuronal cell adhesion molecule); SYN, synapsin. Created with BioRender.com.