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About Dr. Ho

  1. Top of page
  2. About Dr. Ho
  3. “… Exciting Innovations Have Contributed to the Development of My Career in Stem Cell Research”
  4. “We Now Need to Learn More About the Mechanisms Leading to the Maintenance of Pluripotency and More About the Ability of These Cells to Embark on Coordinated Differentiation into Specific Cell Types”
  5. “(Among the German Public) … There Is a General Skepticism Against Genetic Manipulations, Molecular Genetic Technologies, and Human ESC (hESC) Research”
  6. “Understanding the Principles of Self-Renewal and the Differentiation of Stem Cells Is More Important than Exploiting the Stem Cells As Raw Material for Clinical Application”
  7. Supporting Information

Dr. Ho received his medical degree from the University of Heidelberg, Germany, in 1974, and then remained in Heidelberg for an additional 8 years to receive further training in internal medicine and hematology-oncology. He was appointed as Senior Physician at the University of Heidelberg in 1983 and promoted to Professor of Medicine in 1989. In 1990, he moved to North America and was appointed “Full Professor” of Medicine at the University of Ottawa, Canada, and Director of Research and Head of Clinical Trials at the Northeastern Ontario Regional Cancer Center. From 1992–1998, Dr. Ho held the position of Professor and Director of Bone Marrow Transplantation and the Malignant Hematology Program at the University of California, San Diego. He was then recruited back to his alma mater, the University of Heidelberg, where he is currently Professor and Chair of the Department of Medicine V (Hematology, Oncology, and Rheumatology). His research focuses on hematopoietic stem cell transplantation, mechanisms governing self-renewal of normal and leukemic stem cells, and the significance of the bone marrow niche.

Dr. Ho has served as a reviewer and consultant for the Hematology Study Section of the National Institutes of Health and was elected to the “Best Doctors in America” from 1996 to 1998. He is currently a member of the Central Ethics Committee for Stem Cell Research of the National Parliament, Berlin and a Member of the Heidelberg Academy of Sciences.

“… Exciting Innovations Have Contributed to the Development of My Career in Stem Cell Research”

  1. Top of page
  2. About Dr. Ho
  3. “… Exciting Innovations Have Contributed to the Development of My Career in Stem Cell Research”
  4. “We Now Need to Learn More About the Mechanisms Leading to the Maintenance of Pluripotency and More About the Ability of These Cells to Embark on Coordinated Differentiation into Specific Cell Types”
  5. “(Among the German Public) … There Is a General Skepticism Against Genetic Manipulations, Molecular Genetic Technologies, and Human ESC (hESC) Research”
  6. “Understanding the Principles of Self-Renewal and the Differentiation of Stem Cells Is More Important than Exploiting the Stem Cells As Raw Material for Clinical Application”
  7. Supporting Information

“After my training at the Medical Center of the University of Heidelberg, I received a grant from the German ‘Krebshilfe’ to perform research at the Department of Hematology, Royal Free Hospital and School of Medicine, where I met Professor Grant Prentice. I was fascinated by the success of his allogeneic transplantation program. Then, after returning to Heidelberg in 1982, I had the opportunity to work with Martin Körbling as he was in the process of establishing a bone marrow transplantation program at the University of Heidelberg. My continuing enthusiasm for blood stem cell research was further stimulated by the first transplantation of peripheral blood stem cells in lieu of bone marrow transplantation 1985.”

“Now, my research focuses on regulatory mechanisms governing the decision process of self-renewal and differentiation in both normal and leukemic stem cells (LSCs). We have discovered that the stemness of hematopoietic stem cells (HSCs) can only be maintained by cell-cell contact with cellular determinants in the niche. Molecular analysis of these cell-cell contacts has shown that they are mediated by an arsenal of adhesion molecules, some of which are more essential than others. On HSCs, N-cadherin, CD44, and CXCR4 seem to play the most significant roles in this respect. We are now in the process of defining the significance of these adhesion mechanisms in a quantitative manner. We believe that it may be possible to exploit these differences to eliminate LSCs from patients with acute myelogenous leukemia, providing a long-term cure.”

“We Now Need to Learn More About the Mechanisms Leading to the Maintenance of Pluripotency and More About the Ability of These Cells to Embark on Coordinated Differentiation into Specific Cell Types”

  1. Top of page
  2. About Dr. Ho
  3. “… Exciting Innovations Have Contributed to the Development of My Career in Stem Cell Research”
  4. “We Now Need to Learn More About the Mechanisms Leading to the Maintenance of Pluripotency and More About the Ability of These Cells to Embark on Coordinated Differentiation into Specific Cell Types”
  5. “(Among the German Public) … There Is a General Skepticism Against Genetic Manipulations, Molecular Genetic Technologies, and Human ESC (hESC) Research”
  6. “Understanding the Principles of Self-Renewal and the Differentiation of Stem Cells Is More Important than Exploiting the Stem Cells As Raw Material for Clinical Application”
  7. Supporting Information

“I believe that it will be challenging, but extremely valuable, to identify the fundamental cellular and molecular components that control stem cell function. For example, the most significant knowledge that we have gained from 12 years of stem cell research is the ability to reprogram mature body cells to the embryonic stem cell (ESC) stage. Recent studies have identified a set of transcription factors and molecules that can reinstall a pluripotency program in mature somatic cells from animal as well as human origin. These cells behave like ESCs, can differentiate in virtually any cell type including the germ line and are therefore called induced pluripotent stem cells.”

“In addition, by precisely defining the mechanisms that retain the blood stem cells in the narrow niche and hence maintain self-renewal, specific inhibitors to some of these adhesion mechanisms have been developed and applied clinically for stem cell mobilization. Thus, defining specific molecular mechanisms that govern the interaction between stem cells and their niche has led to development of specific inhibitors. One such inhibitor has already been approved in Europe and in the U.S. for the mobilization of blood stem cells. The use of ESC lines in lieu of animal subjects in pharmacotoxicology studies and screening of new drugs in the pharmaceutical industry represents another highly promising field. These are concrete examples of practical applications of stem cell research.”

“Another major issue is that a stem cell paradigm has been suggested for the development of cancer as well as for the formation of metastases. Present evidence indicates that certain human cancers may originate from malignant transformation of stem cells, or alternatively, of progenitors in which the acquired mutations have reinstalled a deregulated self-renewal program. These mutated cells, also called ‘cancer stem cells’, like their normal counterparts, are resistant to conventional chemotherapy and are considered to be the basis for tumor relapse after initial response. It is important to understand the biology of cancer stem cells as compared with that of normal stem cells. Such comparative studies will provide new markers for the identification of cancer stem cells and above all for the development of treatment strategies that target specifically against the cancer stem cells.”

“(Among the German Public) … There Is a General Skepticism Against Genetic Manipulations, Molecular Genetic Technologies, and Human ESC (hESC) Research”

  1. Top of page
  2. About Dr. Ho
  3. “… Exciting Innovations Have Contributed to the Development of My Career in Stem Cell Research”
  4. “We Now Need to Learn More About the Mechanisms Leading to the Maintenance of Pluripotency and More About the Ability of These Cells to Embark on Coordinated Differentiation into Specific Cell Types”
  5. “(Among the German Public) … There Is a General Skepticism Against Genetic Manipulations, Molecular Genetic Technologies, and Human ESC (hESC) Research”
  6. “Understanding the Principles of Self-Renewal and the Differentiation of Stem Cells Is More Important than Exploiting the Stem Cells As Raw Material for Clinical Application”
  7. Supporting Information

Dr. Ho's work involves the use of adult stem cells, however, he provides some interesting insights into the use of hESCs in Germany. “According to the German legislature, human life and “human dignity” starts at the time of fusion of the nuclei from the sperm and the egg cell. Consequently, it is considered that an embryo or a fertilized egg holds the same moral value and deserves the same protection as a born child. Research work using hESCs in Germany is strictly regulated by the “Embryo Protection Law” (Embryonenschutzgesetz). Since 1990, this protection act has banned the use and manipulation of human embryos in medical and biomedical research.”

“However, the rather restrictive Stem Cell Act (Stammzellgesetz) from 2002 was revised in April 2008. Accordingly, ESC lines that were established before May 1, 2007 can now be imported, after a stringent review process, for ‘high priority’ research. There are also regulations governing the use of ESCs for research which are strictly enforced, however, the needs of most ESC researchers are generally somewhat satisfied.”

“Public opinion in Germany regarding stem cell research remains divided. According to one public survey, about 40% of German citizens are in favor of stem cell research, whereas others oppose it. The continuing controversy surrounding hESC research has polarized not only the public, but also scientific communities and politicians. It has also reduced the enthusiasm level of young investigators who may be considering entering the field. Scientists need to be involved in addressing all of these issues, by helping to better educate the general public on the facts about stem cells and by engaging in dialogues with decisions makers in law, ethics, and religion.”

“Understanding the Principles of Self-Renewal and the Differentiation of Stem Cells Is More Important than Exploiting the Stem Cells As Raw Material for Clinical Application”

  1. Top of page
  2. About Dr. Ho
  3. “… Exciting Innovations Have Contributed to the Development of My Career in Stem Cell Research”
  4. “We Now Need to Learn More About the Mechanisms Leading to the Maintenance of Pluripotency and More About the Ability of These Cells to Embark on Coordinated Differentiation into Specific Cell Types”
  5. “(Among the German Public) … There Is a General Skepticism Against Genetic Manipulations, Molecular Genetic Technologies, and Human ESC (hESC) Research”
  6. “Understanding the Principles of Self-Renewal and the Differentiation of Stem Cells Is More Important than Exploiting the Stem Cells As Raw Material for Clinical Application”
  7. Supporting Information

“There are several important potential practical applications for stem cells. For example, ESC lines may be used in lieu of animal subjects in pharmacotoxicology studies and for screening new drugs in the pharmaceutical industry. Novel inhibitors of bone marrow adhesion molecules are in the process of being tested to mobilize stem cells populations in patients. In addition, researchers are working to find markers than can specifically identify cancer stem cells, and treatment strategies that specifically target these cells are being developed.”

“However, it is important for the general public, and young scientists who are considering entering this field, to understand that stem cells are important instruments that we need to understand the physiological as well as the pathologic mechanisms of cell and tissue development. I believe that stem cells will be most valuable as tools to comprehend the mechanisms of cellular self-renewal and differentiation, rather than as simply a means to replace damaged tissues.” 1

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Figure 1. Anthony D. Ho, Professor and Chair of the Department of Medicine, University of Heidelberg. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]

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