With its attractive abilities of self-renewal and differentiation capacity, stem cells are known to have wide applications in regenerative or transplantation therapies and in the development of biological models for understanding disease pathology and drug discovery. However, a high quality and quantity of cells are required for such applications and this can only be obtained through large scale expansion followed by efficient and homogenous differentiation of these cells into their functional derivatives.
Current methods of stem cell culture and differentiation provide limited expansion of these cells and the resulting cells tend to lose their functionality over time or do not achieve a similar morphology as the native cells in the body. One of the key factors that influence stem cell differentiation is the material topography of the substrate where the cells are cultured. However, present fabrication methods are not able to reproduce the complex and heterogeneous native extracellular matrix (ECM) structure which is required for optimal stem cell differentiation.
In this technology, a method of fabricating cell-imprinted substrates mimicking the native cell surface structure is developed. These imprinted silicone substrates with its distinctive topography have been shown to significantly influence cellular gene expressions and differentiation of the cells to specific lineages. Such substrates not only help in increasing the efficiency of stem cell differentiation but also in the maintenance of the viability of the differentiated cells. It also provides a cheap yet reliable, safe and high yield method for controlling stem cell differentiation.
In this technology, a proprietary method of fabricating cell-imprinted substrates with features mimicking native cell surface structure has been developed. This is done through the optimization of the parameters of the curing process required for a precise imprinting of the 3D cell surface structure of cells of a specific cell type. The positive replica is then used in the fabrication of a cell culture substrate with characteristics that are a positive or negative derivation of the original cell surface structure. When stem cells are cultivated onto these substrates, cells of a specific type can be obtained.
This technology has been proven for the reliable and efficient differentiation of mesenchymal stem cells (MSCs) into chondrocytes, keratinocytes as well as tenocytes. More importantly, when induced pluripotent stem cells (iPSCs) are cultured on these substrates, they were found to mature quicker with enhanced functionality. This is primarily because the substrates were able to mimic the native conditions (e.g. forces and pressures) cardiomyocytes experience in the heart. As a result, more mature and functional cardiomyocyte-like cells which have the ability to beat are formed.
Capturing 3D complexity of organs in in-vitro models remains one of the most important challenges in the field of tissue engineering and cell-imprinted substrates may help in this direction. This technology can be used for companies or research institutions interested in stem cell differentiation to a specific lineage either for in vitro modelling or regenerative therapies. It can be also useful for pharmaceutical and/or cosmetic companies interested in drug screening research or functional active ingredients toxicity and efficacy.
Stem cells hold great promise for various applications in cell therapy, tissue engineering, regenerative medicine, pharmaceuticals as well as biotechnology. In turn, there is also growing interest in stem cells differentiation for applications in in vitro modelling, tissue engineered organs as well as for research into disease pathology. It can thus be expected that the demand for such devices will increase. With its ability to replicate the natural stem cell microenvironment which allows for reproducible and biologically relevant research, this device would be valuable in stem cell research studies.