Stem Cells and Regenerative Medicine
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Image supplied by Dr Karen English
Stem Cells
We are currently conducting studies in two broad areas:the immunogenicity of stem cells and the role of stem cells in transplantation tolerance.
Immunogenicity of stem cells and stem cell derived tissues
Research on stem cell therapies and regenerative medicine is progressing rapidly. Although autologous (self) stem cells are clearly the most obvious choice, there are some instances in which the utility of autologous cells may not be possible, for example in patients with genetic defects. Alternatively allogeneic stem cells derived from healthy donors may provide a solution to this problem. However, one of the major aspects of stem cell therapy which is often overlooked is that of immunogenicity. In the past we have concentrated on the immunogenicity of embryonic stem (ES) cells and their differentiated derivatives (specifically insulin producing cell clusters (IPCCs). Through this research we demonstrated that ES cells and IPCCs were recognised by the immune response and targeted by the immune system. Currently we are collaborating with researchers within the European stem cell research consortium Optistem to characterise the immune response to skin and muscle derived progenitor cells.
Mesenchymal stromal cells (MSCs) in transplantation tolerance
MSCs are adult stem cells which have the capacity to modulate immune responses in vitro. Additionally there is some evidence to suggest that MSC can effectively exert their immunosuppressive effect in vivo. Over the past 5 years, MSCs have been effectively used to treat patients with steroid resistant acute GvHD and may prove useful as an immunosuppressive therapy in cell and solid organ transplantation.
Current Studies
We aim to investigate the immunosuppressive effects of human bone marrow and Wharton’s jelly derived MSCs in humanised skin and aorta transplant models. These models have been successfully developed and optimised by the TRIG team over a number of years and allow a unique opportunity to test the suppressive effects of MSCs in a controlled humanised system. http://www.optistem.org/
Induced Pluripotent Stem Cells
Immunogenicity of human iPSC derived cells
The potential of iPS cells is considered to be similar to that of human embryonic stem cells, facilitating the treatment or cure of diseases such as diabetes mellitus, spinal cord injuries, cardiovascular disease, and neurodegenerative diseases, but with the potential added benefit of evading the adaptive immune response that otherwise limits the potential of allogeneic cell-based therapies (Robbins 2010).
However, recent evidence suggests that iPS cells may not be immune privileged. For example, immune response against the integrated viral vectors, mutated mitochondrial genome after long term culture (Ishikawa et al, 2010), and even OCT4 proteins (English and Wood 2010) have been described. Moreover, mouse iPS cell derived teratomas have also been shown to be immunogenic in vivo (Zhao et al., 2011). Therefore, the analysis of the immunogenicity of iPS cells and their derivatives is absolutely necessary.
As the strategy of taking a pluripotent cell in vitro and directing its conversion into a specific differentiated cell fate represents a rational and ongoing approach in regenerative medicine, it is more practical to analyze the immunogenicity of iPS cell derivatives. In our study, human iPS cells are being generated using a non-integrating strategy followed by differentiation into various cell types in vitro. Autologous immune cells will be used to examine the potential immune response against these differentiated iPS cells both ex vivo and in vivo using a humanized murine model developed in the laboratory.
For more information about iPS cells watch the video on the EuroStemCell website... click on the link below for the video,
or visit: www.eurostemcell.org http://www.eurostemcell.org
Scaffolds
Investigating the immune responses to a bioengineered tissue or organ
Tissue engineering aims to produce cells, tissues and organs by seeding cells on supporting scaffold materials. Scaffolds may be synthetic or natural. Natural scaffolds are obtained from the decellularization of animal organs.
Theoretically, they are superior to their synthetic counterparts because the innate vascular network is preserved, as well as all information that are normally present within a cellular organ and are essential to drive cell fate.
Recently, hollow organs as vessels, bladders and windpipes have been manufactured and implanted in humans. It is therefore urgent to characterize the response mounted by the immune system following the implantation of these constructs. When acellular natural scaffolds are implanted in vivo, it is well known that a non specific inflammatory response generates through mechanisms that remain unknown. Our investigations aim to the identification of the pathways activated during this response.