Programs involved with PRM
There are a number of important technologies that are central to the field of Regenerative Medicine. Listed below are the different aspects of the field that will specifically aid us in defining the role and focus of the consortium effort.
Materials Science
One strategy to enhance tissue and organ regeneration is to bridge lesions with biomaterial scaffolds that encourage tissue ingrowth from both sides of the lesion. The scaffolds ideally would contain molecular agents known to stimulate regeneration or neutralize regeneration-inhibiting factors. It is important that the materials that are used are biocompatible so as not to evoke an adverse tissue response. In addition, properties such as biodegradability, permeability, degradability and other characteristics depending on the targeted clinical application may be desirable. Hence the current challenges involve developing materials that possess cellular recognition properties to aid in the control of cell function or cell adhesion. Skin, bone, peripheral nerve, spinal cord, tendon, and blood vessels have all been stimulated to regenerate by various biomaterials, but regeneration is neither perfect nor complete in any case. The obstacle for the Materials Science application is synthesizing scaffolding materials for bioartificial tissues that have the requisite topography, surface properties, growth and differentiative signals to facilitate cell migration, adhesion, proliferation, and differentiation, as well as being moldable into the shapes of various tissues and organs. Available synthetic materials provide mainly mechanical support, migration channels, and adhesive surfaces for cells, and rely on the cells themselves for molecular signals and cues that regulate growth and differentiation. The future will reside at the interface between biology and materials science, where scaffold materials incorporating biological molecules that regulate cell adhesion, proliferation, and differentiation will be designed. It is obvious that expertise in molecular and cellular biology must be joined with biochemistry to create the momentum required.
Cell Biology
Another major area of research involves the cells themselves. Of particular importance for PRM is the identification and isolation of human stem cells among the different tissue lineages. As known these cells can be expanded through many generations and can be potentially induced to differentiate along desired cell lineages. A primary necessity is working out the cell signal/receptor biology required to grow the cells in vitro and directing their differentiation into tissue type phenotypes. In the context of PRM it is critical to maintain the physical properties and architecture of biodegradable scaffolds to support bioartificial tissue construction using stem cells. As yet, it is unknown how many tissues of the body harbor stem or progenitor (more broadly, regeneration-competent) cells that can engage in regeneration. In addition, there is not enough known about the biological signals and cues required to stimulate the adhesion, migration, proliferation, and differentiation of regeneration- competent cells or about the factors that inhibit regeneration. Since failure to undergo proper tissue healing and to regenerate results in scarring, it is important know the specific combinations of molecular signals and receptors that distinguish regeneration from scar tissue formation, including those which could lead to the formation of progenitor cells by dedifferentiation. Although cytokines and growth factors likely have a role in tissue regeneration, appropriate and reliable delivery systems need to be developed for effective targeting and activation. These systems should be capable of localised delivery to specific body sites for prolonged period of time and should be well adapted for delivery of cytokines, growth factors and supplementary drugs, and should exhibit short half-lives and a low risk of toxicity.
In addition, other challenges to the application of this science such as the immunogenicity of biomaterials and cell/ biomaterial composites need to be considered. Another challenge involves the development of bioreactors that can stimulate cell behaviour in a desired way. Last but not least is to be able to achieve tissue specific vascularization of the cell/ biomaterial composite transplant exploiting controlled release of growth factors or enabling cells to express appropriate angiogenic factors
Genomics/Proteomics
High throughput genomics and proteomics analysis using microarray, mass spectrometry, and other sophisticated technologies can be used to study the molecular mechanisms of organ regeneration. Expression analysis can be performed to elucidate genes and proteins involved in organ regeneration by comparing the gene/protein profiles of regenerating tissues before and after damage. Identification of these pathways might provide means to activate self-regeneration ability in humans. Accessibility of various genomic/proteomic resources and expertise in Toronto will foster this type of research.
Imaging
The fate of engineered cells and tissues in vivo can be studied using various imaging techniques to allow the assessment of implanted engineered constructs in a non-invasive or minimally invasive manner.