Reversal of the Developmental Aging of Normal Human Cells Achieved

A new study has shown that the aging of human cells can be reversed may have important implications for the development of new classes of cell-based therapies targeting age-related degenerative disease.

BioTime, Inc. (Alameda, CA, USA), a biotechnology company that develops and markets products in the field of stem cells and regenerative medicine, announced the publication of the study's findings, which was released online March 16, 2010, in the journal Regenerative Medicine in advance of the print publication.

In the article, BioTime and its collaborators demonstrate the successful reversal of the developmental aging of normal human cells. Using exact genetic modifications, normal human cells were induced to reverse both the "clock” of differentiation (the process by which an embryonic stem cell becomes the many specialized differentiated cell types of the body), and the "clock” of cellular aging (telomere length). As a result, aged differentiated cells became young stem cells capable of regeneration.

The research provides insights on the recent controversy over the aged status of induced pluripotent stem (iPS) cells. iPS cell technology has excited the scientific community because it has been demonstrated to be a method of transforming adult human cells back to a state very similar to embryonic stem cells (reversing the process of development) without the use of human embryos. However, recent reports have suggested that iPS cells, although very similar to embryonic stem cells in many respects, may not have the normal replicative potential of embryonic stem cells (meaning, the iPS cells may be prematurely old). This problem has been called "the Achilles heel of iPS cell technology.”

BioTime scientists and their collaborators revealed that many iPS cell lines currently being circulated in the scientific community have short telomeres, meaning that their clock of cellular aging is still set at the age of relatively old cells. However, among these prematurely old cells, other cells can be found with sufficient levels of telomerase (a protein that keeps reproductive cells young) that allow these cells to reverse cellular aging all the way back to the very beginning of the human life cycle.

This research is part of BioTime's broader research strategy to advance the capabilities of the company's proprietary ReCyte technology. ReCyte is being developed as a means of implementing iPS technology on an industrial scale. The study intentionally used older viral-based means of introducing genes. Therefore, BioTime plans additional studies of cellular aging reversal using its proprietary ReCyte technology. BioTime has filed new patent applications on techniques used in the study to reverse the developmental aging of cells and the use of transcriptional reprogramming to produce young cells of many types for use in regenerating tissues affected by aging.

"This is just the beginning of some really fascinating new possibilities for intervening in age-related disease,” said Michael D. West, Ph.D., president and chief executive officer of BioTime, Inc. "We believe that these technologies will have a significant impact on the future of medicine. However, it is important to underscore that much work needs to be done to translate these findings into safe and efficacious therapies.”

"At the National Institute on Aging, we reviewed many proposals from leading gerontologists seeking means to understand and intervene in the biology of aging,” said Robert N. Butler, M.D., founding director of the U.S. National Institute on Aging (Bethesda, MD, USA), now president of the International Longevity Center (New York, NY, USA), and board member of BioTime. "These are just the type of basic discoveries that if funded on a larger scale, could help us ward off the enormous wave of healthcare expenditures coming our way as a result of the aging baby boom population.”

Regenerative medicine refers to the development and use of therapies based on human embryonic stem (hES) cell or induced pluripotent stem (iPS) cell technology. These therapies will be designed to regenerate tissues afflicted by degenerative diseases. The great scientific and public interest in regenerative medicine lies in the potential of hES and iPS cells to become all of the cell types of the human body. Many scientists therefore believe that hES and iPS cells have considerable potential as sources of new therapies for a host of currently incurable diseases such as diabetes, Parkinson's disease, heart failure, arthritis, muscular dystrophy, spinal cord injury, macular degeneration, hearing loss, liver failure, and many other disorders where cells and tissues become dysfunctional and need to be replaced.

Since human embryonic stem cells are derived from discarded human embryos created in the process of in vitro fertilization (IVF), their use in research has been controversial. However, induced pluripotent (iPS) stem cells can be created using noncontroversial adult cells, such as skin cells, rather than embryonic cells. The alteration of specific genes in adult cells allows them to be transformed into iPS cells that are very similar to hES cells.

BioTime plans eventually to utilize these technologies for human therapeutic applications. However, the technologies reported in BioTime's scientific article are early stage research findings. Cell-based therapeutics require years of extensive preclinical testing and development before being used in an effort to treat humans.

BioTime is a biotechnology company focused on regenerative medicine and blood plasma volume expanders. BioTime develops and markets research products in the field of stem cells and regenerative medicine through its wholly owned subsidiary Embryome Sciences, Inc. BioTime also plans to develop therapeutic products in China for the treatment of ophthalmologic, skin, musculoskeletal system, and hematologic diseases, including the targeting of genetically modified stem cells to tumors as an innovative means of treating currently incurable forms of cancer through its subsidiary BioTime Asia.

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