Chondrogenic commitment of human umbilical cord blood-derived mesenchymal stem cells in collagen matrices for cartilage engineering

Abstract

Umbilical cord blood (UCB) is a promising alternative source of mesenchymal stem cells (MSCs), because UCB-MSCs are abundant and harvesting them is a painless non-invasive procedure. Potential clinical applications of UCB-MSCs have been identified, but their ability for chondrogenic differentiation has not yet been fully evaluated. The aim of our work was to characterize and determine the chondrogenic differentiation potential of human UCB-MSCs (hUCB-MSCs) for cartilage tissue engineering using an approach combining 3D culture in type I/III collagen sponges and chondrogenic factors. Our results showed that UCB-MSCs have a high proliferative capacity. These cells differentiated easily into an osteoblast lineage but not into an adipocyte lineage. Furthermore, BMP-2 and TGF-β1 potentiated chondrogenic differentiation, as revealed by a strong increase in mature chondrocyte-specific mRNA (COL2A1, COL2B, ACAN) and protein (type II collagen) markers. Although growth factors increased the transcription of hypertrophic chondrocyte markers such as COL10A1 and MMP13, the cells present in the neo-tissue maintained their phenotype and did not progress to terminal differentiation and mineralization of the extracellular matrix after subcutaneous implantation in nude mice. Our study demonstrates that our culture model has efficient chondrogenic differentiation, and that hUCB-MSCs can be a reliable source for cartilage tissue engineering.

Avoidance of total knee arthroplasty in early osteoarthritis of the knee with intra-articular implantation of autologous activated peripheral blood stem cells versus hyaluronic acid: A randomized controlled trial with differential effects of growth factor addition

“…The ease of procurement, collection of large numbers, and favorable costs favor PB, BM, and AT in that order. The ultimate autologous stem cell option is of course UC blood and tissues, due to ease of collection, storage, costs, safety, and availability, but there have as yet not been any autologous uses in OA employing that source [35]. The only clinical comparative study between stem cell types in cartilage regeneration is the study of Skowroński and Rutka [36] showing superior results for PBSC versus BM.…”

“…Potential feasible autologous stem cell sources for cartilage regeneration treatments include hematopoietic stem cells (HSCs) in bone marrow (BM), hG-CSF-activated/stimulated peripheral blood (PB) (the mainstay choice in stem cell collection and transplantation since many decades further ensuring patient safety [23]), and theoretically umbilical cord blood (UCB). Trabecular bone, cartilage, adipose tissue (AT), and, theoretically, umbilical cord (UC) tissues [35] also contain autologous stem cells with chondrogenic potential. The ease of procurement, collection of large numbers, and favorable costs favor PB, BM, and AT in that order.…”

Human umbilical cord‐derived scaffolds for cartilage tissue engineering

“…33 In healthy articular cartilage, proliferation of chondrocytes is resisted whereas GAG production increases. 32 DNA content measurement revealed that there were no significant differences in the DNA content between the different groups after 21 days of culture. GAG/DNA showed that although the amount of synthesized GAG was significantly increased in the presence of TGF-β, there were no significant differences between tissue and gelatin scaffolds.…”

“…10 FTIR data proved an increase in the cross-linking degree in both tissue and gelatin scaffolds after treating with EDC/NHS. 32 Additionally, it seems that a considerable increase of COL II as the main component of the cartilage matrix is more likely to moderate this expression difference. 27 Thus, sensing matrix stiffness by the cells is likely to modulate differentiation into the various cell lineages.…”

“…On the other hand, TGF-β induction led to significant upregulation of ALP and COL X, but this can be explained by pervious findings that showed TGF-β upregulates both chondrogenic and hypertrophic markers. 32 Additionally, it seems that a considerable increase of COL II as the main component of the cartilage matrix is more likely to moderate this expression difference. In other words, when COL II/COL X ratio was evaluated, it was demonstrated that this proportion was decreased in the presence of TGF-β.…”