OSTEOGENIC COMMITMENT AND DIFFERENTIATION OF HUMAN MESENCHYMAL STEM CELLS BY LOW-INTENSITY PULSED ULTRASOUND STIMULATION.

Author: Costa V1, Carina V1, Fontana S2, De Luca A1, Monteleone F2, Pagani S3, Sartori M4, Setti S5, Faldini C6, Alessandro R2, Fini M3,4, Giavaresi G1,3
Affiliation:
1Rizzoli Orthopedic Institute, Innovative Technological Platforms for Tissue Engineering, Theranostic and Oncology, Palermo, Italy.
2Biology and Genetics Unit, Department of Biopathology and Medical Biotechnologies, University of Palermo, Italy.
3Rizzoli Orthopedic Institute, Laboratory of Preclinical and Surgical Studies, Bologna, Italy.
4Rizzoli Orthopedic Institute, Laboratory BITTA, Bologna, Italy.
5IGEA SpA, Carpi (Modena), Italy.
6Rizzoli Orthopedic Institute, 2nd Orthopaedic and Traumatologic Clinic, Bologna, Italy.
Conference/Journal: J Cell Physiol.
Date published: 2017 Jun 16
Other: Special Notes: doi: 10.1002/jcp.26058. [Epub ahead of print] , Word Count: 237


Low-intensity pulsed ultrasound (LIPUS) as an adjuvant therapy in in vitro and in vivo bone engineering has proven to be extremely useful. The present study aimed at investigating the effect of 30 mW/cm2 LIPUS stimulation on commercially available human mesenchymal stem cells (hMSCs) cultured in basal or osteogenic medium at different experimental time points (7d, 14d, 21d). The hypothesis was that LIPUS would improve the osteogenic differentiation of hMSC and guarantying the maintenance of osteogenic committed fraction, as demonstrated by cell vitality and proteomic analysis. LIPUS stimulation (a) regulated the balance between osteoblast commitment and differentiation by specific networks (activations of RhoA/ROCK signaling and upregulation of Ribosome constituent/Protein metabolic process, Glycolysis/Gluconeogenesis, RNA metabolic process/Splicing and Tubulins); (b) allowed the maintenance of a few percentage of osteoblast precursors (21d CD73 + /CD90 + : 6%; OCT-3/4 + /NANOG + /SOX2 + : 10%); (c) induced the activation of osteogenic specific pathways shown by gene expression (early: ALPL, COL1A1, late: RUNX2, BGLAP, MAPK1/6) and related protein release (COL1a1, OPN, OC), in particular in the presence of osteogenic soluble factors able to mimic bone microenvironment. To summarize, LIPUS might be able to improve the osteogenic commitment of hMSCs in vitro, and, at the same time, enhance their osteogenic differentiation. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

KEYWORDS: low-intensity pulsed ultrasound; mesenchymal stem cells; osteoblast differentiation; osteogenic commitment; proteomic analysis

PMID: 28621452 DOI: 10.1002/jcp.26058

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