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The self-assembly approach of tissue engineering for in vitro production of human tissue- and organ-specific constructs

Julie Fradette1, 2, Meryem Safoine1, 2, Maryse Proulx1, 2, Maud Vallée1, 2, Cindy Hayward1, 2, François A. Auger1, 2, Kim Aubin1, 2 and Valérie Trottier1, 2
  • 1 CHU de Québec - Université Laval Research Centre, Canada
  • 2 Département de Chirurgie and Centre de recherche en organogénèse expérimentale de l’Université Laval, Canada

Introduction: Annually, more than 5.7 million reconstructive surgery procedures are performed in the USA. Tissue engineering being a promising alternative to autologous grafting, many cell sources/biomaterials have been investigated in order to engineer tissues with optimal properties. Recently, a trend towards the use of natural biological matrices is noticeable. Accordingly, our core technology is based on the self-assembly approach of tissue engineering, which exploits the capacity of mesenchymal cells (MSC) to secrete and assemble matrix elements upon ascorbic acid and serum supplementation, leading to manipulatable cell sheets and suturable constructs devoid of exogenous biomaterials. Goal: Assess the potential of human MSC from various origins for the in vitro engineering of connective tissues based on their intrinsic capacity for matrix production and assembly.

Methods: MSC from adipose tissue (ASC), bone marrow (BM-MSC), umbilical cord Wharton’s jelly (WJ-MSC) as well as dermal fibroblasts (DF) were used for tissue production in presence of serum (FBS). Tissue reconstruction with ASC or DF was also directly compared using a novel serum-free culture system. Indeed, the use of animal derivative products should be substituted to ensure the best safety profile.

Results: MSC from different origins revealed distinct capacities with regards to their ability to produce matrix leading to cell sheets and tissue formation. ASC- and DF-constructs generally featured an increased thickness when compared to BM-MSC and WJ-MSC constructs. Immunolabelings for matrix elements such as collagens and fibronectin indicated similarities shared between tissues produced using the different MSC. Our most recent work using serum-free medium (SFM) during the entire tissue production indicates that ASC constructs were 3.9 fold thicker and 1.9 fold less contractile in comparison with the tissues produced with 10% FBS. Cell sheets cultured in SFM could be manipulated earlier, diminishing production time by 50%. Assessment of functionality revealed a higher secretion of the angiogenic factors Ang-1, VEGF and PAI-1 (respectively 1.5, 6.4 and 3.0 fold, p<0.001, ELISA) by the connective tissues produced in SFM, reflecting their pro-healing potential. When connective tissues produced by ASC were compared to those engineered from DF using this SFM culture system, ASC constructs were 2.9 fold thicker and produced more Ang-1 (6.9x) and PAI-1 (7.0x) per tissue area.

Conclusion: MSC from various tissues can be used to generate tissue-specific stroma with therapeutic properties. In particular, tissues featuring excellent structural and secretory properties are obtained when using ASC. Optimized serum-free culture results in the accelerated production of functional soft tissues. Taken together, these human tissues have extensive surgical applications as graft substrates and can also act as stromal support for skin and bladder reconstruction.

Supported by CIHR

Keywords: Extracellular Matrix, Tissue Engineering, stem cell

Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.

Presentation Type: Poster

Topic: Biomaterials in constructing tissue substitutes

Citation: Fradette J, Safoine M, Proulx M, Vallée M, Hayward C, Auger FA, Aubin K and Trottier V (2016). The self-assembly approach of tissue engineering for in vitro production of human tissue- and organ-specific constructs. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02990

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Received: 28 Mar 2016; Published Online: 30 Mar 2016.