In the last 20 years, more than 1,500 gene therapy clinical trials have been approved worldwide targeting a variety of indications, from inherited monogenic diseases to acquired conditions such as cancer, cardiovascular and infectious diseases. However, concerns about the safety and efficacy of gene therapy pharmaceuticals justify the development of alternative strategies to ensure the clinical translation of this still promising field. In particular, ex vivo gene therapy strategies using autologous adult stem cells coupled to three-dimensional (3D) porous scaffolds show great promises in preclinical studies. Developments in the fields of biomaterial sciences and tissue engineering have already helped understanding how we can harness to regenerative potential of many cell types to create artificial tissues and organs and vastly improve the engraftment of ex vivo manipulated adult stem cells. In this article, we will review the current state of the art in tissue engineering by exploring the various types of clinically available biomaterials and the methods used to process them into complex 3D scaffolds. We will then review how these technologies are applied in cell-based gene therapy and identify novel avenues of research that may benefit patients in the near future.
"Three-dimensional biodegradable scaffolds
seeded with stem/progenitor cells provides one of
the most interesting strategies in the field of biomaterials (29). This study has described the fabrication
and cytocompatibility of porous collagen
scaffolds by freeze-drying, and the effect of pore
structure and laminin as biophysical and biochemical
cues on hiPSC-NPs behavior. "
[Show abstract][Hide abstract] ABSTRACT: Biomaterial technology, when combined with emerging human induced pluripotent stem cell (hiPSC) technology, provides a promising strategy for patient-specific tissue engineering. In this study, we have evaluated the physical effects of collagen scaffolds fabricated at various freezing temperatures on the behavior of hiPSC-derived neural progenitors (hiPSC-NPs). In addition, the coating of scaffolds using different concentrations of laminin was examined on the cells.
Initially, in this experimental study, the collagen scaffolds fabricated from different collagen concentrations and freezing temperatures were characterized by determining the pore size, porosity, swelling ratio, and mechanical properties. Effects of cross-linking on free amine groups, volume shrinkage and mass retention was also assessed. Then, hiPSC-NPs were seeded onto the most stable three-dimensional collagen scaffolds and we evaluated the effect of pore structure. Additionally, the different concentrations of laminin coating of the scaffolds on hiPSC-NPs behavior were assessed.
Scanning electron micrographs of the scaffolds showed a pore diameter in the range of 23-232 μm for the scaffolds prepared with different fabrication parameters. Also porosity of all scaffolds was >98% with more than 94% swelling ratio. hiPSC-NPs were subsequently seeded onto the scaffolds that were made by different freezing temperatures in order to assess for physical effects of the scaffolds. We observed similar proliferation, but more cell infiltration in scaffolds prepared at lower freezing temperatures. The laminin coating of the scaffolds improved NPs proliferation and infiltration in a dose-dependent manner. Immunofluorescence staining and scanning electron microscopy confirmed the compatibility of undifferentiated and differentiated hiPSC-NPs on these scaffolds.
The results have suggested that the pore structure and laminin coating of collagen scaffolds significantly impact cell behavior. These biocompatible three-dimensional laminin-coated collagen scaffolds are good candidates for future hiPSC-NPs biomedical nerve tissue engineering applications.
"The injection of mesenchymal or cardiac stem cells in vivo into a damaged organ is currently under investigation (Blin et al., 2010; Noort et al., 2010). Alternatively, the engraftment of engineered tissue substitutes produced by seeding stem cells on biodegradable, biocompatible scaffolds has been proposed as a more suitable solution to repair injured tissues (Coutu et al., 2009). Natural (fi brin, chitosan, collagen, hyaluronic acid) and synthetic (polylactic and polylacticcoglycolic acid, polycaprolacton) polymers have been proposed as com ponents of scaffolds for tissue engineering. "
[Show abstract][Hide abstract] ABSTRACT: The main goal in the last few years in cardiac research has been to isolate cardiac potential stem cells from adult myocardium and to demonstrate their differentiation potential. We have previously demonstrated that c-Kit positive cardiac stem cells are able to organize themselves into a tissue-like cell mass. In this 3D mass, they can produce a high concentration of natural extracellular matrix, can create vessels, a capsule and, with the help of an Open-pore Polylactic Acid scaffold, many cells can organize an elementary myocardium. Drawing from this background, we decided to design and use poly-lactic scaffolds and the model of the athymic Nude-Foxn1(nu) mouse to evaluate the extent of the myogenic vs endothelial differentiation in vivo, and to evaluate the presence or the absence of a foreign body reaction.
Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia 01/2010; 115(1-2):65-9.
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