Chondrogenic Priming Adipose-Mesenchymal Stem Cells for Cartilage Tissue Regeneration
Chondrocytes lose their ability to produce cartilaginous matrix during multiplication in culture through repeated passages, resulting in inferior tissue phenotype. To overcome the limited amount of primary chondrocytes, we aimed to determine the optimal culture condition for in vitro/in vivo cartilage regeneration using human adipose-derived mesenchymal stem cells (AMSCs).
To evaluate the effects exerted by the chondrocytic culture condition on AMSC, we utilized chondrocyte conditioned medium (CM) and/or co-culture methods to prime and differentiate AMSCs. We evaluated ultimate in vivo engineered cartilage with primed AMSCs with that of chondrocytes. To examine the link between conditioned factors and proliferation/differentiation, cell cycle progression of AMSCs were examined using 5-ethynyl-2′-deoxyuridine (EdU), and gene expression was monitored.
We report that AMSCs can be stimulated to become chondrogenic cells when expanded with chondrocyte CM. Polymeric scaffolds co-seeded with CM- expanded AMSCs and primary chondrocytes resulted in in vivo cartilaginous tissues with similar biochemical content to constructs seeded with chondrocytes alone.
These results indicate that chondrocyte CM consists of suitable morphogenetic factors that induce the chondrogenic priming of AMSCs for cartilage tissue engineering.
KEY WORDSauricular chondrocytes cartilage co-culture human adipose derived mesenchymal stem cells tissue engineering
- 4.Brittberg M, Tallheden T, Sjogren-Jansson B, Lindahl A, Peterson L. Autologous chondrocytes used for articular cartilage repair: an update. Clin Orthop Relat Res 2001;S337–48.Google Scholar
- 5.Abrahamsson CK, Yang F, Park H, Brunger JM, Valonen PK, Langer R, et al. Chondrogenesis and mineralization during in vitro culture of human mesenchymal stem cells on three-dimensional woven scaffolds. (PMID: 20673022) Tissue Eng Part A. 2010;16:3709–18.Google Scholar
- 16.Ni YF, Li XF, Liu Y, Lei ZJ, Lu Q. In vivo chondrogenesis by co-culture of rabbit bone marrow-derived mesenchymal stem cells and chondrocytes. J Clin Rehab Tiss Eng Res. 2008;12:3185–8.Google Scholar
- 17.Worster AA, Brower-Toland BD, Fortier LA, Bent SJ, Williams J, Nixon AJ. Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor-beta1 in monolayer and insulin-like growth factor-I in a three-dimensional matrix. J Orthop Res. 2001;19:738–49.PubMedCrossRefGoogle Scholar
- 25.Lee JS, Im GI. Influence of Chondrocytes on the Chondrogenic Differentiation of Adipose Stem Cells. (PMID: 20597811) Tissue Eng Part A. 2010;16:3569–77.Google Scholar