Stem cell research: What progress has been made, what is its potential?

Sep 10, 2010

The use of stem cells for research and their possible application in the treatment of disease are hotly debated topics. In a special issue of Translational Research published this month an international group of medical experts presents an in-depth and balanced view of the rapidly evolving field of stem cell research and considers the potential of harnessing stem cells for therapy of human diseases including cardiovascular diseases, renal failure, neurologic disorders, gastrointestinal diseases, pulmonary diseases, neoplastic diseases, and type 1 diabetes mellitus.

Personalized cell therapies for treating and curing human diseases are the ultimate goal of most stem cell-based research. But apart from the scientific and technical challenges, there are serious ethical concerns, including issues of privacy, consent and withdrawal of consent for the use of unfertilized eggs and embryos. "Publication of this special issue could not have been more timely, given the recent federal district court injunction against federal support for human embryonic ," said Dr. Jeffrey Laurence, M.D., Professor of Medicine at Weill Cornell Medical College and Editor in Chief of Translational Research. "This court order stops all pending federal grants and contracts, as well as their peer review, suspending over 20 major research programs and over $50 million in federal funding for them," he noted. As Dr. Francis Collins, NIH director, stated, "This decision has the potential to do serious damage to one of the most promising areas of biomedical research, just at the time when we were really gaining momentum."

Through a series of authoritative articles authors highlight basic and clinical research using human embryonic and . Common themes include preclinical evidence supporting the potential therapeutic use of stem cells for acute and chronic diseases, the challenges in translating the preclinical work to clinical applications, as well as the results of several randomized clinical trials. Authors stress that considerable preclinical work is needed to test the potential of these approaches for translation to the clinical setting.

In considering the potential for clinical applications, some common challenges and questions persist. The issue focuses on critical questions such as whether the use of any stem cell population will increase the risk of cancer in the recipient and whether the goal of stem cell therapy is to deliver cells that can function as organ-specific cells.

Writing in a commentary on advances and challenges in translating stem cell therapies for clinical diseases, Michael A. Matthay, MD, Cardiovascular Research Institute, University of California San Francisco, notes that "the progress that has been achieved in the last 30 years in using allogeneic and autologous hematopoietic stem cells for the effective treatment of hematologic malignancies should serve as a model of how clinical applications may yet be achieved with , induced pluripotent stem cells, endothelial progenitor cells, and mesenchymal stem cells. Although several challenges exist in translating stem cell therapy to provide effective new treatments for acute and chronic human diseases, the potential for developing effective new cell-based therapies is high."

KEY POINTS:

Bone marrow and circulating stem/progenitor cells for regenerative cardiovascular therapy
Mohamad Amer Alaiti, Masakazu Ishikawa, and Marco A. Costa
Despite initial promising pilot studies, only small improvements in a few clinical outcomes have been seen using stem cell therapies to treat heart disease in the acute or chronic setting. But new research, and a multitude of new pilot studies, may alter this scenario.

New therapies for the failing heart: trans-genes versus trans-cells
Vincenzo Lionetti, and Fabio A. Recchia
This review presents key aspects of cardiac gene therapy and stem cell therapy for the failing heart. Recent discoveries in stem cell biology may revitalize gene therapy and, vice versa.

Endothelial lineage cell as a vehicle for systemic delivery of cancer gene therapy
Arkadiusz Z. Dudek
Rather than focusing on the cancer cell itself, attention to blood vessels feeding the cancerous cells, lined by endothelial cells, presents a new avenue of cancer therapy. The author discusses recent evidence that endothelial progenitor cells may be useful in treating primary and metastatic tumors. Targeted cancer gene therapy using endothelial lineage cells to target tumor sites and produce a therapeutic protein has proven feasible.

Pluripotent stem cell-derived natural killer cells for cancer therapy
David A. Knorr, and Dan S. Kaufman
The potential value as well as challenges of using human embryonic stem cells and induced pluripotent stem cells is to provide platforms for new cell-based therapies to treat malignant diseases are discussed.

Translation of stem cell therapy for neurological diseases
Sigrid C. Schwarz, and Johannes Schwarz
Early clinical work to develop cell-based therapy for neurologic disorders such as Parkinson's disease is discussed.

Stem cell technology for the treatment of acute and chronic renal failure
Christopher J. Pino, and H. David Humes
The authors cover the relative potential and success to date of embryonic or induced pluripotent stem cells as therapies for regenerating functional kidney tissue.

Stem cell approaches for the treatment of type 1 diabetes mellitus
Ryan T. Wagner, Jennifer Lewis, Austin Cooney, and Lawrence Chan
The authors provide a thorough discussion of the potential of using either embryonic stem cells or induced pluripotent stem cells to generate functional islet cells, the cells of the pancreas which normally make insulin, but fail to do so in severe forms of diabetes.

Intestinal stem cells and epithelial-mesenchymal interactions in the crypt and stem cell niche
Anisa Shaker, and Deborah C. Rubin
Both preclinical and early clinical trials have been carried out with allogeneic bone marrow-derived mesenchymal stem cells to treat steroid refractory acute and chronic inflammatory bowel diseases, particularly Crohn's disease.

Stem cells and cell therapy approaches in lung biology and diseases
Viranuj Sueblinvong, and Daniel J. Weiss,
Cell-based therapies with embryonic or adult have emerged as potential novel approaches for several devastating and otherwise incurable lung diseases, including emphysema, pulmonary fibrosis, pulmonary hypertension, and acute respiratory distress syndrome.

Explore further: Iberian pig genome remains unchanged after five centuries

More information: The articles appear in Translational Research, The Journal of Laboratory and Clinical Medicine, Volume 156, Issue 3 (September 2010) entitled Stem Cells: Medical Promises and Challenges. www.translationalres.com/

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