Peer-Reviewed Journal Details
Mandatory Fields
Ansboro, S,Hayes, JS,Barron, V,Browne, S,Howard, L,Greiser, U,Lalor, P,Shannon, F,Barry, FP,Pandit, A,Murphy, JM
2014
April
J Control Release
A chondromimetic microsphere for in situ spatially controlled chondrogenic differentiation of human mesenchymal stem cells
Published
Optional Fields
Microspheres Delivery vehicle Mesenchymal stem cell Chondrogenesis Osteoarthritis Tissue engineering PHARMACOLOGICALLY ACTIVE MICROCARRIERS HYALURONIC-ACID HYDROGELS MURINE KNEE-JOINT FACTOR-BETA 3 EXTRACELLULAR-MATRIX TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSIENT EXPOSURE PLGA MICROSPHERES INTRAARTICULAR INJECTIONS PROTEOGLYCAN SYNTHESIS
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Human mesenchymal stem cells (hMSCs) have been identified as a viable cell source for cartilage tissue engineering. However, to undergo chondrogenic differentiation hMSCs require growth factors, in particular members of the transforming growth factor beta (TGF-beta) family. While in vitro differentiation is feasible through continuous supplementation of TGF-beta 3, mechanisms to control and drive hMSCs down the chondrogenic lineage in their native microenvironment remain a significant challenge. The release of TGF-beta 3 from an injectable microsphere composed of the cartilage-associated extracellular matrix molecule hyaluronan represents a readily translatable approach for in situ differentiation of hMSCs for cartilage repair. In this study, chondromimetic hyaluronan microspheres were used as a growth factor delivery source for hMSC chondrogenesis. Cellular compatibility of the microspheres (1.2 and 14.1 mu m) with hMSCs was shown and release of TGF-beta 3 from the most promising 14.1 mu m microspheres to control differentiation of hMSCs was evaluated. Enhanced accumulation of cartilage-associated glycosaminoglycans by hMSCs incubated with TGF-beta 3-loaded microspheres was seen and positive staining for collagen type II and proteoglycan confirmed successful in vitro chondrogenesis. Gene expression analysis showed significantly increased expression of the chondrocyte-associated genes, collagen type II and aggrecan. This delivery platform resulted in significantly less collagen type X expression, suggesting the generation of a more stable cartilage phenotype. When evaluated in an ex vivo osteoarthritic cartilage model, implanted hMSCs with TGF-beta 3-loaded HA microspheres were detected within cartilage fibrillations and increased proteoglycan staining was seen in the tissue. In summary, data presented here demonstrate that TGF-beta 3-bound hyaluronan microspheres provide a suitable delivery system for induction of hMSC chondrogenesis and their use may represent a clinically feasible tissue engineering approach for the treatment of articular cartilage defects. (C) 2014 Elsevier B.V. All rights reserved.
10.1016/j.jconrel.2014.01.023
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