Chemotaxis of human articular chondrocytes and mesenchymal stem cells

Abstract

Migration of chondrocytes and mesenchymal stem cells (MSCs) may be important in cartilage development, tissue response to injury, and in tissue engineering. This study analyzed growth factors and cytokines for their ability to induce migration of human articular chondrocytes and bone marrow-derived mesenchymal stem cells in Boyden chamber assays. In human articular chondrocytes serum induced dose- and time-dependent increases in cell migration. Among a series of growth factors and cytokines tested only PDGF induced a significant increase in cell migration. The PDGF isoforms AB and BB were more potent than AA. There was an aging-related decline in the ability of chondrocytes to migrate in response to serum and PDGF. Human bone marrow MSC showed significant chemotaxis responses to several factors, including FBS, PDGF, VEGF, IGF-1, IL-8, BMP-4, and BMP-7. In summary, these results demonstrate that directed cell migration is inducible in human articular chondrocytes and MSC. PDGF is the most potent factor analyzed, and may be useful to promote tissue integration during cartilage repair or tissue engineering.

In SituTissue Regeneration: Chemoattractants for Endogenous Stem Cell Recruitment

“…PDGF has two receptor dimers, a and b. PDGF-AA binds a/a receptors, PDGF-AB binds a/a and a/b receptors, and PDGF-BB binds a/a, a/b, and b/b receptors. 46 In vitro, PDGF-AA, 47,48 PDGF-BB, 47 and PDGF-AB 47,49 were shown to be potent chemoattractants for human bMSC, with PDGF-BB generating the strongest response. 47 PDGF-AB also stimulated chemotaxis by ovine bMSC.…”

“…by human bMSC, 48,70 suggesting that their role in fracture healing may include bMSC recruitment. BMP-2 and -7 delivery have been studied extensively in animal models, and it has been approved as a clinical treatment for fracture nonunions and large segmental defects.…”

Heparin modification of a biomimetic bone matrix modulates osteogenic and angiogenic cell response in vitro

“…Here, the development of scaffold materials which are able to enrich cells with regenerative potential in the affected area is a promising approach. Both processes, cell attraction and vascularisation, can be stimulated by chemoattractive factors (Richardson et al, 2001;Kanczler et al, 2008;Mishima and Lotz, 2008;Thieme et al, 2009). With the aim of utilising the natural binding properties of heparin for functionalisation of mineralised collagen matrices with such factors, we have developed two approaches for heparin-modification: integration during material synthesis ('in situ') or addition after scaffold-fabrication ('post') König et al, 2014).…”

Skeletal Regeneration by Mesenchymal Stem Cells: What Else?

“…Attracting factors include BMPs (Frenkel et al, 1996), hepatocyte growth factor (HGF) (Takebayashi et al, 1995), IGF-1 (Chang et al, 2003), TGF-β (Chang et al, 2003), PDGF (Fujita et al, 2004), FGF (Hidaka et al, 2006), fibronectin, fibrin and collagen type I (Maniwa et al, 2001). However, results remain contradictory for some of these factors, as testing of human chondrocytes revealed no effects for BMP-2, BMP-4, BMP-7, IGF and TGF-β in other studies (Mishima &, Lotz, 2008), being IGF-1, PDGF (Fiedler et al, 2004;Ozaki et al, 2007;Ponte et al, 2007) and VEGF the ones that induced higher response (Mishima & Lotz, 2008). Effects of GFs vary in vitro and in vivo, regarding animal species and specimens' age, among other aspects.…”

“…Besides, the lack of filling and the possible dead space between cylindrical grafts can limit the repair quality and integrity. Lane et al transplanted autologous osteochondral grafts into sheep knee joints and reported the lack of integration of the cartilage, which determined the persistence of gaps through the full thickness in all the specimens (Mishima et al, 2008). Fig.…”