Stem Cells as Biomaterials of the Future

STEM CELLS AS BIOMATERIALS OF THE FUTURE: AN OVERVIEW OF SOME STEM CELL ISSUES

Philip H. Schwartz

National Human Neural Stem Cell Resource

Children’s Hospital of Orange County


Few advances in science have generated as much controversy as the recent discovery that human embryonic stem cells (hESCs) can be harvested from the preimplantation embryo. The potential of hESCs to replace dead or damaged cells in any tissue of the body may herald the advent of a new field of medicine that can deliver cures for diseases now thought to be incurable. In addition, hESCs offer a new model system for studies of basic mechanisms in normal and abnormal developmental biology as well as for drug discovery studies. These remarkable cells have captured the imagination of scientists and clinicians alike and given a new sense of hope to patients. Although the public controversy surrounding the use of hESCs arises primarily from the technique required to harvest these cells—destruction of the human embryo—logistical, technical, and legislative hurdles to the use of hESCs also exist. In this overview presentation, issues surrounding basic cell culture techniques, implantation safety, funding sources, legislation, stem cell sources, and transplantation are discussed.

PROPAGATING AND DIFFERENTIATING HUMAN EMBRYONIC STEM CELLS

Steven L. Stice

University of Georgia


The Stice research group at the University of Georgia derived three of the hESC lines (BG01, BG02, and BG03) that have been approved by the NIH using mechanical dissection of the original colonies. Mechanical passaging entails the selection of specific areas of hESCs, followed by separation of



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Proceedings from the Workshop on Biomedical Materials at the Edge: Challenges in the Convergence of Technologies Stem Cells as Biomaterials of the Future STEM CELLS AS BIOMATERIALS OF THE FUTURE: AN OVERVIEW OF SOME STEM CELL ISSUES Philip H. Schwartz National Human Neural Stem Cell Resource Children’s Hospital of Orange County Few advances in science have generated as much controversy as the recent discovery that human embryonic stem cells (hESCs) can be harvested from the preimplantation embryo. The potential of hESCs to replace dead or damaged cells in any tissue of the body may herald the advent of a new field of medicine that can deliver cures for diseases now thought to be incurable. In addition, hESCs offer a new model system for studies of basic mechanisms in normal and abnormal developmental biology as well as for drug discovery studies. These remarkable cells have captured the imagination of scientists and clinicians alike and given a new sense of hope to patients. Although the public controversy surrounding the use of hESCs arises primarily from the technique required to harvest these cells—destruction of the human embryo—logistical, technical, and legislative hurdles to the use of hESCs also exist. In this overview presentation, issues surrounding basic cell culture techniques, implantation safety, funding sources, legislation, stem cell sources, and transplantation are discussed. PROPAGATING AND DIFFERENTIATING HUMAN EMBRYONIC STEM CELLS Steven L. Stice University of Georgia The Stice research group at the University of Georgia derived three of the hESC lines (BG01, BG02, and BG03) that have been approved by the NIH using mechanical dissection of the original colonies. Mechanical passaging entails the selection of specific areas of hESCs, followed by separation of

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Proceedings from the Workshop on Biomedical Materials at the Edge: Challenges in the Convergence of Technologies these areas from the colony using a fine-drawn pipette and subsequent placement of these cells on a new mouse embryonic fibroblast feeder layer. The group has determined that mechanically passaged hESCs have normal karyotypes at passages 41, 50, 62, 74, 100, and 105 under identical cell culture conditions. However, this method is labor-intensive and requires specialized training. Other materials and methods for passaging hESCs have therefore been developed for more general use of these cells in the scientific community. This presentation discusses these techniques and the need for new materials and methods for propagating hESCs, as well as the Stice research group’s recent advances in directing in vitro differentiation of hESCs to neural fates. CARDIAC REGENERATIVE STRATEGIES USING HEMATOPOIETIC AND HUMAN EMBRYONIC STEM CELLS Michael A. Laflamme University of Washington Because the adult human heart has little regenerative capacity, irreversible injury to the myocardium, such as by infarction, typically results in the formation of a noncontractile scar and often initiates progressive heart failure. Because of the limited number of suitable donor hearts for transplantation, there has been much recent interest in cellular approaches to cardiac repair—that is, cell transplantation. A number of cell types have been considered for this application, including skeletal muscle precursors, adult stem cells, and cardiomyocytes derived from hESCs. The Murry Laboratory at the University of Washington has explored the capacity of marrow-derived hematopoietic stem cells to regenerate the infarcted heart. Researchers found that, after direct injection into the infarct, none of these adult stem cells transdifferentiated into cardiomyocytes. Because hESCs have an unquestioned capacity to differentiate into cardiomyocytes in vitro, the Murry Laboratory has focused on examining the potential of hESC-derived cardiomyocytes to form new human myocardium in the hearts of immunodeficient rats. In experiments involving transplantation into the uninjured hearts of athymic rats, researchers found that hESC-derived cardiomyocytes indeed formed substantial, highly proliferative, and, at least at later time points, exclusively cardiac grafts within the rat heart. While ongoing studies have demonstrated the successful formation of similar human cardiac implants within experimentally infarcted hearts, this preclinical work has also high-lighted important but perhaps surmountable challenges for such cell-based

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Proceedings from the Workshop on Biomedical Materials at the Edge: Challenges in the Convergence of Technologies therapies, including the need for improved strategies to achieve a homogeneous cardiac preparation and enhanced cell survival after implantation. NEW TISSUES FROM HUMAN MESENCHYMAL STEM CELLS Mark F. Pittenger Osiris Therapeutics, Inc. Mesenchymal stem cells (MSCs) can be isolated from many tissues; bone marrow provides a convenient and renewable source. Human mesenchymal stem cells (hMSCs) can be grown in culture, resulting in the production of billions of these multipotential cells, which can then be formulated for various tissue repair and regeneration purposes. Osiris Therapeutics has experience with formulating therapies for orthopedic applications—bone, meniscus, and cartilage—as well as therapies for aiding bone marrow transplantation and cardiac therapies following infarction. Much of this work has been described in peer-reviewed publications. Over the past several years, Osiris Therapeutics has evaluated the ability of MSCs to engraft in recipients without immunological matching. This use of allogeneic stem cells for tissue repair in unrelated recipients has exciting implications for the ready availability of adult stem cell therapies in the clinic. Previous methods for the application of autologous stem cells have required harvesting the patient’s own tissue, followed by isolation and expansion of the patient’s autologous MSCs over a three- to four-week period. This presentation will review the evidence for the multilineage potential of hMSCs and their ability to avoid rejection when implanted in the allogeneic host. The mechanism by which allogeneic MSCs interact with different isolated immune cells is presented, along with several tissue repair models.