Functional properties of cartilaginous tissues engineered from infrapatellar fat pad-derived mesenchymal stem cells

Abstract

Articular cartilage has a poor intrinsic capacity for self repair. The advent of autologous chondrocyte implantation has provided a feasible method to treat cartilage defects.However, the associated drawbacks with the isolation and expansion of chondrocytes from autologous tissue has prompted research into alternative cell sources such as mesenchymal stem cells (MSCs) which have been found to exist in the bone marrow as well as other joint tissues such as the infrapatellar fat pad (IFP), synovium and within the synovial fluid itself. In this work we assessed the chondrogenic potential of IFP derived porcine cells over a six week period in agarose hydrogel culture in terms of mechanical properties, biochemical content and histology. It was found that IFP cells underwent robust chondrogenesis as assessed by glycosaminoglycan (1.47 ± 0.22 % w/w) and collagen (1.44 ± 0.22 % w/w) accumulation after 42 days of culture. The 1Hz dynamic modulus of the engineered tissue at this time-point was 272.8 kPa (± 46.8). The removal of TGF-β3 from culture after 21 days was shown to have a significant effect on both the mechanical properties and biochemical content of IFP constructs after 42 days, with minimal increases occurring from day 21 to day 42 without continued supplementation of TGF-β3. These findings further strengthen the case that the IFP may be a promising cell source for putative cartilage repair strategies.3

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

“…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). 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).…”

“…We have previously shown that MSCs isolated from infrapatellar fat pad tissue are a viable alternative cell source for cartilage tissue engineering (Buckley et al 2010a;Buckley et al 2010b;Vinardell et al 2010). It is evident from the literature that stem cell expansion conditions can significantly influence their subsequent chondrogenic capacity (Tsutsumi et al 2001;Bianchi et al 2003;Solchaga et al 2005;Khan et al 2008;Solchaga et al 2010).…”

“…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.…”

A review of decellularized stem cell matrix: a novel cell expansion system for cartilage tissue engineering

“…ASCs from infrapatellar fat pad (IPFP) are a promising source of stem cells for chondrogenesis (Wickham et al, 2003;Khan et al, 2007;Khan et al, 2008) and cartilage tissue engineering (Dragoo et al, 2003;Jurgens et al, 2009;Buckley et al, 2010). Our recent study assessed whether DSCM expansion could improve ASC proliferation and chondrogenic potential (He and Pei, 2011a).…”

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].…”