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

• Published in: Stem cell research & therapy Vol. 10; no. 1; pp. 356 - 11
• Main Authors: Cabrera-Pérez, Raquel, Monguió-Tortajada, Marta, Gámez-Valero, Ana, Rojas-Márquez, Raquel, Borràs, Francesc Enric, Roura, Santiago, Vives, Joaquim
• Format: Journal Article
• Language: English
• Published: London BioMed Central 28.11.2019; BioMed Central Ltd; BMC
• Subjects: Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Bone marrow; Bone marrow transplantation; Bone morphogenetic protein 2; Bone morphogenetic proteins; Bone regeneration; Cell Biology; Cell culture; Chromatography; Cloning; Comparative analysis; Ethics; Gene expression; Genes; Good Manufacturing Practice; Life Sciences; Manufacturers; Medical equipment industry; Mesenchymal stem cells; Mesenchymal stromal cells; Mesenchyme; Orthopedics; Osteogenesis; Osteogenic differentiation; Penicillin; Proteins; Regenerative medicine; Regenerative Medicine/Tissue Engineering; Scientific equipment industry; Secretome; Signal transduction; Software; Stem Cells; Stromal cells; Surgery; Transforming growth factor-b1; Transforming growth factors; Wharton’s jelly; United States; Spain; Mesenchymal stromal cells; Bone marrow; Wharton’s jelly; Bone regeneration; Osteogenic differentiation
• ISSN: 1757-6512; 1757-6512
• DOI: 10.1186/s13287-019-1450-3

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.