Centre For Regenerative Medicine Research Articles

Cytomics and regenerative medicine

THE key focus of regenerative medicine lies in the reconstitution of damaged or dysfunctional cells, tissues, or organs. Stimulation of the body's own regenerative potential, the connection to artificial materials and surface structures and extracorporeal tissue engineering of cells and tissues are particular challenges (1, 2). Success in the derivation of stem cell lines has opened up a new area of research in biomedicine. Human stem cells not only raise hope for cell replacement therapies but also provide a potential novel system to better understand early human normal development, model human abnormal development and disease, and perform drug screening and toxicity studies. The realization of these potentials, however, depends on expanding our knowledge about the cellular and molecular mechanisms that regulate self renewal and lineage specification. Cytomics has received great attention during the last several years as it allows us to quantitatively analyze a great number of individual cells, their constituents, and their intracellular and functional interactions in cellular systems (cytomes) (3-12). Exhaustive knowledge extraction from multiparametric assays and multiple tests are the prerequisite for cytomics. This novel approach for unsupervised data analysis opens the chance to find the most important parameters which describe best the cell systems. Individual cells of an organ may be specifically equipped to perform specific tasks. Deciphering cell systems on the individual cell level may yield key information to understand function or dysfunction. A combination of state-of-the-art approaches, including cytomics, proteomics, and genomics, will be instrumental in moving the field forward, ultimately lending invaluable knowledge to research areas in regenerative medicine. Analyzing the data about cellular structures, cytomics—the systems biological discipline for cell population analysis—provides a plethora of information and is the ideal partner of regenerative medicine. Realizing the idea “from the molecule to the patient” gives an opportunity to speed up the introduction of this knowledge and offers chemical compounds, proteins, and other biomolecules, cells and tissues as instruments and products for a wide variety of biotechnological and biomedical applications. Cytomics combines different disciplines and will promote the development of innovative therapies and diagnostic methods. Regenerative medicine can be improved by the precision of the measurements with focus on single cell analysis. Analyzing from cell constituents to whole body imaging techniques, cytometry covers the field from molecules through subcellular components, cells, tissues, and organs to live analysis of small animals (13, 14). It harbors the promise to substantially impact on various fields of biomedicine, like regenerative and predictive medicine (3, 5). As the number of scientific data is rising exponentially, new data analysis tools and strategies for cytomics take the lead and get closer to application. Cytomics may strongly support the quantitative data selection, thus strengthening the rationale for biomedicine. This year's 14th Leipziger Workshop highlighted applications in regenerative medicine and focused on how cytometry has contributed to the characterization of primary cells, cell cultures, and their development. The Leipziger Workshop series began in 1995. From 2003 on, it embraced cytomics as its major topic (15). After the first cytomics workshop, we started to combine cytomics with various biomedical disciplines: regenerative and predictive medicine of cardiovascular disease (2004) (5), systems biology and clinical cytomics (2005) (16), cytomics and the human cytome project (2006) (17), cytomics and translational medicine (2007) (18, 19), and cytomics and nanobioengineering (2008) (20). Consequently, the key aspects of the 14th Leipziger Workshop from April 2–4, 2009 in Leipzig (www.leipziger-workshop.de) were cytomics and regenerative medicine. The high relevance of this combination of two biomedical disciplines with a strong standing in technology was highly appreciated. Over 90 scientists attended this year's meeting from more than 10 countries. It included keynote lectures and tutorials; there were overall 33 oral and 17 poster presentations (see abstracts). So far, this has been one of the most successful meetings in the history of the Leipziger Workshop. The number of participants has constantly increased over the last several years and will further prosper in future. The high attendance and anticipation of the workshop shows the increased demand and interest in cytomics. This year's workshop received substantial support from the Biological and Biomedical Center of the University of Leipzig (BBZ, www.bbz.uni-leipzig.de), the newly founded Translational Center for Regenerative Medicine (TRM, www.trm.uni-leipzig.de) Leipzig and several exhibitors who were also directly involved in the teaching program (www.leipziger-workshop.de).

Interview: Virus-Free Induction of Induced Pluripotent Stem Cells

Dr Nagy is currently a Senior Scientist at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Professor in the Department of Molecular Genetics at the University of Toronto and Investigator at the McEwen Centre for Regenerative Medicine. He also holds a Tier I Canada Research Chair in Stem Cells and Regeneration. His research focuses on several areas of interest, which include: functional studies of genes belonging to families with known roles in vessel formation; development of sophisticated genetic manipulation tools in the mouse model; applying genetics to cancer research; derivation, differentiation and genetic modification of both mouse and human embryonic stem cells; and reprogramming of somatic cells to pluripotent stem cells. Dr Nagy's research is currently funded by the National Cancer Institute of Canada, Genome Canada, Stem Cell Network, NSERC and the NIH.

Bone Marrow Transplantation

Stem cells are the centre for regenerative medicine. Given a right signal these undifferentiated cells have a remarkable potential to develop into specialized cell types (blood cells, heart cells etc.) in the human body. Stem cells, therefore, can be used in cell-based therapies to replace/repair damaged tissues and/or organs. Ongoing research in the area of stem cells focuses on their potential application (both embryonic stem cells and adult stem cells) to create specialized cells and replace the damaged ones. Hence, this cutting-edge technology might lead to new ways of detecting and treating diseases. Stem cell transplantation can be considered as an option for the treatment of certain type of cancers. This medical procedure can also be used to treat neurological diseases, autoimmune diseases, heart diseases, liver diseases, metabolic disorders, spinal cord injury etc. The present review, therefore, focuses on the growing use of stem cell transplantation in regenerative medicine to treat a variety of diseases. This review also provides the current status of the field with a particular emphasis on bone marrow transplantation.

Stems cells and regeneration: Special Review Issue

Stems cells and regeneration: Special Review Issue

Meeting Report: Adult Mesenchymal Stem Cells in Regenerative Medicine Conference, August 2007

MSCs have been in the news recently in part because of the number of clinical trials reporting beneficial effects of these cells in a variety of clinical settings. It was therefore timely that the Cleveland Clinic, Case Western Reserve University, and the University Hospitals of Case Medical Center and the National Center for Regenerative Medicine, Cleveland, hosted the first of what I hope will be a regularly repeated conference on MSC. The 3-day conference drew over 300 participants from more than 100 different centers worldwide and included representatives from research laboratories, translational research centers, and clinical trial groups. More than 30 different countries were represented. Industrial representatives from the major players in this field were well represented, as were venture capitalists and regulatory agencies. The meeting was well organized, and it was clear that considerable thought and effort had gone into planning the sequence of talks and building the sessions. The early sessions focused on basic science findings, whereas the latter sessions focused on MSC products that will soon be in the market. Issues covered included the source of cells, methods of isolation and propagation, identifying mechanisms of action, the regulatory issues faced by autologous and allogenic users, the difficulties of organizing clinical trials, and obtaining funding for the same (Fig. 1). It was exciting to see how quickly this field has grown and how this has altered the landscape for adult stem cells. Given the wealth of information presented and the range of topics covered, I will not even attempt to summarize all the findings in a brief report. I hope that the organizers will disseminate the information in the form of proceedings in an electronic format. Herein, I will just comment on some personal highlights of the meeting. Perhaps the most important discussion was on developing common nomenclature and standards, something that I personally feel is critical for MSCs and, indeed, the entire stem cell field. The MSC meeting provided an unprecedented opportunity for all the major players in the field to discuss in a public forum the need for a set of standards in defining the population of cells and assessing the quality of these cells for clinical use. The need is clearly urgent, as data from one set of studies cannot be used in another unless equivalence of the two cell types used is established. The other major highlight for this attendee was the talk presented by Dr. Mills, CEO of Osiris, on the MSC product pipeline and early phase II/III results. I believe this will be the first allogeneic cell therapeutic, and its success will no doubt accelerate the entry of other companies into this field. Several other promising avenues of therapeutic intervention were discussed in a variety of different clinical diseases, ranging from modulating the immune response in Crohn disease to utilizing the normal differentiation ability of MSCs to enhance bone repair, breast reconstruction, and cartilage repair to examining the transdifferentiation potential of MSCs to treat neurological disorders. Dr. Luis Solchaga provided some intriguing and exciting data that showed unambiguously that fibroblast growth factor (FGF) acts to enhance proliferation with retention of the multilineage capacity of the MSCs. Additional data on platelet-derived growth factor and other growth factors suggest that this may likely be unique to the FGF family of growth factors. The data appear dramatic enough that the Cleveland Clinic is likely to use FGF expanded cells for future clinical trials. Perhaps the most novel application of MSCs was to utilize MSCs as a source of cells for screening and drug discovery. Dr. Keith Haskell from Pfizer presented data on using an RNA interference screen to identify G protein-coupled receptors that might be important in self-renewal and/or adipogenesis. Their success is no doubt a harbinger of many such efforts by big Pharma and may provide additional impetus to developing methodology to grow and propagate stem-progenitor cells in a defined medium. Another exciting extension of the use of MSCs that was discussed was in veterinary medicine. Vet-Stem, a small biotechnology company, presented data on tendon repair in race horses and joint repair in other species. It is very important for the field to have appropriate data from some large animal species, and the data sets that Vet-Stem is developing will be Figure 1. Session topics at Adult Mesenchymal Stem Cells in Regenerative Medicine Conference, August 2007. Abbreviation: GVH, graft versus host.

A conversation with Ian Wilmut, Director of the Centre for Regenerative Medicine, University of Edinburgh

Dolly the sheep came not from the union of sperm and egg but from the mammary cell of one sheep and the unfertilized egg of another. Her birth, more than 10 years ago showed that nuclei from specialized adult cells can be reprogrammed into all the cells of an organism.

Dose a pharmaceutical company have any interest in the field of developing regenerative medicine?

A patient needs the frontier medicine, for example, regenerative medicine, gene therapy and pharmacogenomics. We believe that the regenerative medicine fits for that needs. So, we will discuss about researching and developing a regenerative medicine.At first, we have to prepare the infrastructure of clinical trial and investment for developing the regenerative medicine. And we will have to build the consortium that contains clinical research center and support center for regenerative medicine. We will call that consortium “regenerative medicine development consortium”.The clinical research center has a cell processing center, cell and tissue supply center, cell resource development center and cell & tissue bank.A support center for regenerative medicine has new concept hospital, rehabilitation center, job training center, volunteer organization in support of regenerative medicine and patients.