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Tee R.,OBrien Institute | Lokmic Z.,OBrien Institute | Lokmic Z.,University of Melbourne | Morrison W.A.,OBrien Institute | And 3 more authors.
ANZ Journal of Surgery | Year: 2010

In heart failure, post-myocardial infarction and some congenital cardiac anomalies, organ transplantation is the only effective cure. Shortage of organ donors and complications of orthotopic heart transplant remain major challenges to the modern field of transplantation. Tissue engineering using cell-based strategies presents itself as a new way of generating functional myocardium. Engineering functional myocardium de novo requires an abundant source of cells that can form cardiomyocytes. These cells may be used with biocompatible scaffold materials to generate a contractile myocardium. Lastly, to sustain the high metabolism of the construct, a functional vasculature needs to be developed with the forming cardiac tissue. This review provides an update on the progress of stem cell research in the context of cardiac tissue development, types of biomaterials used in cardiac tissue engineering (CTE) and currently employed strategies for vascularization in CTE. In addition, a brief overview of strategies utilized in CTE is provided. © 2010 The Authors. ANZ Journal of Surgery © 2010 Royal Australasian College of Surgeons.


Choi Y.S.,OBrien Institute | Choi Y.S.,University of Melbourne | Dusting G.J.,OBrien Institute | Dusting G.J.,University of Melbourne | And 10 more authors.
Journal of Cellular and Molecular Medicine | Year: 2010

Human adipose-derived stem cells (ASCs) may differentiate into cardiomyocytes and this provides a source of donor cells for tissue engineering. In this study, we evaluated cardiomyogenic differentiation protocols using a DNA demethylating agent 5-azacytidine (5-aza), a modified cardiomyogenic medium (MCM), a histone deacetylase inhibitor trichostatin A (TSA) and co-culture with neonatal rat cardiomyocytes. 5-aza treatment reduced both cardiac actin and TropT mRNA expression. Incubation in MCM only slightly increased gene expression (1.5- to 1.9-fold) and the number of cells co-expressing nkx2.5/sarcomeric α-actin (27.2% versus 0.2% in control). TSA treatment increased cardiac actin mRNA expression 11-fold after 1 week, which could be sustained for 2 weeks by culturing cells in cardiomyocyte culture medium. TSA-treated cells also stained positively for cardiac myosin heavy chain, α-actin, TropI and connexin43; however, none of these treatments produced beating cells. ASCs in non-contact co-culture showed no cardiac differentiation; however, ASCs co-cultured in direct contact co-culture exhibited a time-dependent increase in cardiac actin mRNA expression (up to 33-fold) between days 3 and 14. Immunocytochemistry revealed co-expression of GATA4 and Nkx2.5, α-actin, TropI and cardiac myosin heavy chain in CM-DiI labelled ASCs. Most importantly, many of these cells showed spontaneous contractions accompanied by calcium transients in culture. Human ASC (hASC) showed synchronous Ca2+ transient and contraction synchronous with surrounding rat cardiomyocytes (106 beats/min.). Gap junctions also formed between them as observed by dye transfer. In conclusion, cell-to-cell interaction was identified as a key inducer for cardiomyogenic differentiation of hASCs. This method was optimized by co-culture with contracting cardiomyocytes and provides a potential cardiac differentiation system to progress applications for cardiac cell therapy or tissue engineering. © 2010 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.


Choi Y.S.,OBrien Institute | Choi Y.S.,University of Melbourne | Matsuda K.,OBrien Institute | Dusting G.J.,OBrien Institute | And 6 more authors.
Biomaterials | Year: 2010

Cardiac tissue engineering offers promise as a surgical approach to cardiac repair, but requires an adequate source of cardiomyocytes. Here we evaluate the potential for generating human cardiac muscle cells in vivo from adipose-derived stem cells (ASC) by co-implanting in a vascularised tissue engineering chamber with inducing rat cardiomyocytes (rCM). Co-implantation (ASC-rCM) was compared with rCM or ASC controls alone after 6 weeks. Immunostaining using human nucleus specific antibody and cardiac markers revealed several fates for ASC in the chamber; (1) differentiation into cardiomyocytes and integration with co-implanted rCM; (2) differentiation into smooth muscle cells and recruitment into vascular structures; (3) adipogenic differentiation. ASC-rCM and ASC groups grew larger tissue constructs than rCM alone (212 ± 25 μl, 171 ± 16 μl vs. 137 ± 15 μl). ASC-rCM and rCM groups contracted spontaneously at up to 140 bpm and generated a 10-15-fold larger volume of cardiac muscle (14.5 ± 4.8 μl and 18.5 ± 2.6 μl) than ASC alone group (1.3 ± 0.5 μl). Vascular volume in ASC-rCM group was twice that of the rCM group (28.7 ± 5.0 μl vs. 14.8 ± 1.8 μl). The cardiac tissue engineered by co-implanting human ASC with neonatal rCM showed in vivo plasticity of ASC and their cardiomyogenic potential in tissue engineering. ASC contribution to vascularisation also promoted the growth of engineered tissue, confirming their utility in this setting. © 2009 Elsevier Ltd. All rights reserved.


Poon C.J.,OBrien Institute | Pereira E. Cotta M.V.,OBrien Institute | Pereira E. Cotta M.V.,University of Melbourne | Sinha S.,OBrien Institute | And 8 more authors.
Acta Biomaterialia | Year: 2013

The ability to generate controlled amounts of adipose tissue would greatly ease the burden on hospitals for reconstructive surgery. We have previously shown that a tissue engineering chamber containing a vascular pedicle was capable of forming new fat; however, further refinements are required to enhance fat formation. The development and maintenance of engineered adipose tissue requires a suitable source of growth factors and a suitable scaffold. A hydrogel derived from adipose tissue may fulfil this need. Subcutaneous fat was processed into a thermosensitive hydrogel we refer to as adipose-derived matrix (ADM). Protein analysis revealed high levels of basement membrane proteins, collagens and detectable levels of growth factors. Adipose-derived stem cells exposed to this hydrogel differentiated into adipocytes with > 90% efficiency and in vivo testing in rats showed significant signs of adipogenesis after 8 weeks. ADM's adipogenic properties combined with its simple gelation, relatively long shelf life and its tolerance to multiple freeze-thaw cycles, makes it a promising candidate for adipose engineering applications. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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