Next Article in Journal
An Update on Mitochondrial Ribosome Biology: The Plant Mitoribosome in the Spotlight
Previous Article in Journal
Extracellular Vesicles–Encapsulated MicroRNA-125b Produced in Genetically Modified Mesenchymal Stromal Cells Inhibits Hepatocellular Carcinoma Cell Proliferation
Open AccessArticle

Substrate Stiffness Modulates Renal Progenitor Cell Properties via a ROCK-Mediated Mechanotransduction Mechanism

1
Centre for Research, Transfer and High Education for the development of DE NOVO Therapies (DENOTHE), Viale Morgagni 50, 50136 Florence, Italy
2
Department of Clinical and Experimental Biomedical Sciences “Mario Serio”, University of Florence, Viale Morgagni 50, 50134 Florence, Italy
3
Nephrology Unit and Meyer Children’s University Hospital, Viale Pieraccini 24, 50139 Florence, Italy
*
Author to whom correspondence should be addressed.
Cells 2019, 8(12), 1561; https://doi.org/10.3390/cells8121561
Received: 26 September 2019 / Revised: 27 November 2019 / Accepted: 2 December 2019 / Published: 3 December 2019
(This article belongs to the Section Stem Cells)
Stem cell (SC)-based tissue engineering and regenerative medicine (RM) approaches may provide alternative therapeutic strategies for the rising number of patients suffering from chronic kidney disease. Embryonic SCs and inducible pluripotent SCs are the most frequently used cell types, but autologous patient-derived renal SCs, such as human CD133+CD24+ renal progenitor cells (RPCs), represent a preferable option. RPCs are of interest also for the RM approaches based on the pharmacological encouragement of in situ regeneration by endogenous SCs. An understanding of the biochemical and biophysical factors that influence RPC behavior is essential for improving their applicability. We investigated how the mechanical properties of the substrate modulate RPC behavior in vitro. We employed collagen I-coated hydrogels with variable stiffness to modulate the mechanical environment of RPCs and found that their morphology, proliferation, migration, and differentiation toward the podocyte lineage were highly dependent on mechanical stiffness. Indeed, a stiff matrix induced cell spreading and focal adhesion assembly trough a Rho kinase (ROCK)-mediated mechanism. Similarly, the proliferative and migratory capacity of RPCs increased as stiffness increased and ROCK inhibition, by either Y27632 or antisense LNA-GapmeRs, abolished these effects. The acquisition of podocyte markers was also modulated, in a narrow range, by the elastic modulus and involved ROCK activity. Our findings may aid in 1) the optimization of RPC culture conditions to favor cell expansion or to induce efficient differentiation with important implication for RPC bioprocessing, and in 2) understanding how alterations of the physical properties of the renal tissue associated with diseases could influenced the regenerative response of RPCs. View Full-Text
Keywords: renal progenitor cells; Young’ modulus; tissue engineering; regenerative medicine; Rho-kinase renal progenitor cells; Young’ modulus; tissue engineering; regenerative medicine; Rho-kinase
Show Figures

Figure 1

MDPI and ACS Style

Melica, M.E.; La Regina, G.; Parri, M.; Peired, A.J.; Romagnani, P.; Lasagni, L. Substrate Stiffness Modulates Renal Progenitor Cell Properties via a ROCK-Mediated Mechanotransduction Mechanism. Cells 2019, 8, 1561.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop