Growth Factor Priming of Synovium-Derived Stem Cells for Cartilage Tissue Engineering

Abstract

This study investigated the potential use of synovium-derived stem cells (SDSCs) as a cell source for cartilage tissue engineering. Harvested SDSCs from juvenile bovine synovium were expanded in culture in the presence (primed) or absence (unprimed) of growth factors (1 ng/mL transforming growth factor-b 1 , 10 ng/mL plateletderived growth factor-bb, and 5 ng/mL basic fibroblast growth factor-2) and subsequently seeded into clinically relevant agarose hydrogel scaffolds. Constructs seeded with growth factor-primed SDSCs that received an additional transient application of transforming growth factor-b 3 for the first 21 days (release) exhibited significantly better mechanical and biochemical properties compared to constructs that received sustained growth factor stimulation over the entire culture period (continuous). In particular, the release group exhibited a Young's modulus (267 -96 kPa) approaching native immature bovine cartilage levels, with corresponding glycosaminoglycan content (5.19 -1.45%ww) similar to native values, within 7 weeks of culture. These findings suggest that SDSCs may serve as a cell source for cartilage tissue engineering applications.

Expansion in the presence of FGF-2 enhances the functional development of cartilaginous tissues engineered using infrapatellar fat pad derived MSCs

“…In this study the withdrawal of TGF-after 21 days did not enhance the subsequent functional development of the engineered construct, consistent with our previous findings (Buckley et al 2010b). A strategy of withdrawing TGF-from the culture media may eventually overcome the problem of diminishing matrix synthesis in long-term culture, but may depend, among other factors, on further optimization of stem cell isolation and expansion conditions (Sampat et al 2011) and the cell seeding density (Huang et al 2009). Another concern is that the long-term culture data presented here could be indicative of some inherent inability of cartilaginous constructs engineered using IFP derived stem cells to generate a fully functional tissue once implanted into a defect, or whether these results are merely a result of suboptimal in vitro culture conditions.…”

“…One explanation for the failure to retain high levels of proteoglycan within a tissue engineered construct could be the failure to develop a collagenous network capable of retaining these key matrix The temporal profiles of sGAG and collagen release to the media suggest that matrix synthesis peaked shortly before or around day 28 of culture. Cartilage tissue engineering studies using chondrocytes (Byers et al 2008), and more recently synovium derived stem cells (Sampat et al 2011), have demonstrated that withdrawal of TGF-from the media after 2-3 weeks of culture enhances long-term matrix accumulation. In this study the withdrawal of TGF-after 21 days did not enhance the subsequent functional development of the engineered construct, consistent with our previous findings (Buckley et al 2010b).…”

“…MSCs derived from non-cartilaginous knee joint tissues such as the infrapatellar fat pad (IFP) (Dragoo et al 2003;English et al 2007;Jurgens et al 2009;Buckley et al 2010a; Buckley et al 2010b) and synovium (Sakaguchi et al 2005;Yokoyama et al 2005; Mochizuki et al 2006;Pei et al 2008;Pei et al 2009;Sampat et al 2011) have been shown to possess significant chondrogenic potential. One of the key challenges in cartilage tissue engineering is ensuring sufficient functionality of the construct to be implanted which is capable of withstanding the challenging mechanical environment of the joint.…”

Controlled release of transforming growth factor-β3 from cartilage-extra-cellular-matrix-derived scaffolds to promote chondrogenesis of human-joint-tissue-derived stem cells

“…Mesenchymal stem cells or multipotent stromal cells (MSCs) isolated from various tissues such as bone marrow [1][2][3][4][5][6][7], subcutaneous fat [8][9][10][11], infrapatellar fat pad (IFP) [6,[12][13][14][15][16][17][18][19][20][21] and synovium [9,[22][23][24][25][26], combined with various scaffolds and hydrogels, have been explored for tissue regeneration. The IFP is a particularly attractive source of MSCs for this type of application as it is easy to access and provides a large number of cells with the potential to generate cartilaginous tissue [12,13,20].…”

A Comparison of the Functionality andIn VivoPhenotypic Stability of Cartilaginous Tissues Engineered from Different Stem Cell Sources

“…24 Further, when joint-derived stem cells are encapsulated in agarose hydrogels, they generate cartilaginous tissues whose mechanical functionality increases with time in culture. [30][31][32] Therefore, agarose would appear to be a promising material to facilitate both the development of a functional engineered cartilaginous graft in vitro and maintenance of a chondrogenic phenotype in vivo.…”