Osteogenic commitment of Wharton’s jelly mesenchymal stromal cells: mechanisms and implications for bioprocess development and clinical application

Abstract

Cèl·lules estromals mesenquimals; Gelatina de Wharton; Diferenciació osteogènica

Células estromales mesenquimales; Gelatina de Wharton; Diferenciación osteogénica

Mesenchymal stromal cells, Wharton’s jelly; Osteogenic differentiation

Background Orthopaedic diseases are one of the major targets for regenerative medicine. In this context, Wharton’s jelly (WJ) is an alternative source to bone marrow (BM) for allogeneic transplantation since its isolation does not require an invasive procedure for cell collection and does not raise major ethical concerns. However, the osteogenic capacity of human WJ-derived multipotent mesenchymal stromal cells (MSC) remains unclear. Methods Here, we compared the baseline osteogenic potential of MSC from WJ and BM cell sources by cytological staining, quantitative real-time PCR and proteomic analysis, and assessed chemical and biological strategies for priming undifferentiated WJ-MSC. Concretely, different inhibitors/activators of the TGFβ1-BMP2 signalling pathway as well as the secretome of differentiating BM-MSC were tested. Results Cytochemical staining as well as gene expression and proteomic analysis revealed that osteogenic commitment was poor in WJ-MSC. However, stimulation of the BMP2 pathway with BMP2 plus tanshinone IIA and the addition of extracellular vesicles or protein-enriched preparations from differentiating BM-MSC enhanced WJ-MSC osteogenesis. Furthermore, greater outcome was obtained with the use of conditioned media from differentiating BM-MSC. Conclusions Altogether, our results point to the use of master banks of WJ-MSC as a valuable alternative to BM-MSC for orthopaedic conditions.

Work in our laboratory is supported by the Spanish Cell Therapy Network (TerCel, expedient No. RD16/0011/0028 and RD16/00111/0006), Ministerio de Ciencia Innovación y Universidades de España (Instituto de Salud Carlos III, expedient No. PI19/01788), Fundació la Marató de TV3 (expedient number: 122831), and ISCIII-REDinREN (RD16/0009 Feder Funds), and developed in the context of AdvanceCat with the support of ACCIÓ (Catalonia Trade & Investment; Generalitat de Catalunya) under the Catalonian ERDF operational programme (European Regional Development Fund) 2014-2020. FEB is a researcher from Fundació Institut de Recerca en Ciències de la Salut Germans Trias i Pujol, supported by the Health Department of the Catalan Government (Generalitat de Catalunya). Our laboratory is awarded by the Generalitat de Catalunya as Consolidated Research Groups (ref. 2017-SGR-719, 2017-SGR-301 and 2017-SGR-483).