Highlights from the 2012 Buck Symposium: Stem Cell Research and Aging

By Benjamin Blackwell and Kevin Perrott

Benjamin Blackwell, Research Associate
Lunyak lab at the Buck Institute

The 2012 Buck Symposium on Stem Cell Research and Aging brought together some of the world’s cutting-edge researchers, but more importantly, it provided a space for the formal convergence of stem cell-based regenerative medicine and aging research.  Although intrinsically linked by a common goal, these two fields have been separated historically and conceptually.  During the meeting, there was a strong underlying sense that an unbiased synthesis of basic aging research and stem cell engineering will be the next crucial milestone in the advancement toward effective healthspan extension.

The symposium started off with some extremely promising research from Lisa Ellerby’s group, highlighting her recent progress in cell replacement therapy for Huntington’s disease. Dr. Ellerby presented a method for correcting the genetic mutation that causes Huntington’s, so that a patient’s own cells can be removed, genetically “fixed”, and then differentiated into the exact cell type that is lost during Huntington’s disease progression. This is a crucial step toward the development of patient-specific cell replacement therapies for Huntington’s disease.

The basic biology of stem cells was highlighted as Paul Robson from the Genome Institute of Singapore showcased some surprising data on the potency of human blastocyst-derived stem cells.  This research showed that these stem cells, derived from the inner cell mass of the developing embryo, may in fact be totipotent (capable of forming all cell types including the placenta) as opposed to pluripotent (capable of forming any cell type in the body).  Susan Fisher of UCSF showed that within the embryonic inner cell mass, from which most embryonic stem cell lines are derived, there is a significant variation in their potency and in the subset of genes that they are actively using.

The meeting then turned toward what most people consider the most exciting future prospect for stem cell-based regenerative medicine, which is their use in supplementing or regenerating the aging/diseased brain. After a few presentations on the biology of neural development and aging/disease, the first day ended with a beautiful keynote presentation by Ole Isacson of Harvard Medical School on new treatments for Parkinson’s disease (PD) patients based on stem and iPS (induced pluri-potent stem) cells. Dr. Isacson presented tear-jerking video evidence of obvious improvement in a PD patient during a cell replacement trial that induced a sense of hopeful enthusiasm going into the final day of the symposium.

Riding on the energy of Dr. Isacson’s keynote speech, Friday morning opened up with some groundbreaking work into the complex signaling networks and epigenetic (on top of genetics) mechanisms that regulate stem cell aging, which are emerging as novel targets to allow the engineering of cell-based therapies.  These novel insights into the vast complexity of stem cell aging were highlighted by recent observations from the lab of Victoria Lunyak that show how ancient virus-derived DNA, once thought to be evolutionary “junk”, is tightly involved in the regulation of stem cell senescence, a dormant or non-functional state that increases upon aging.

The meeting then switched gears toward different strategies for manipulating stem cells to create new therapeutic tools as well as new disease models and drug-screening systems.  This session was highlighted by exciting research from the lab of Xianmin Zeng of the Buck Institute, which showed promising results for the treatment of PD.  Her lab has created a way in which iPS cells can be created from patients without integrating artificial DNA into the genome of the patients’ cells (a common method).  She then showed how these cells could be transformed into the dopamine-producing neurons that are lost upon PD progression.

The meeting hosted a number of exciting researchers who were not mentioned above, but more exciting was the overarching spirit of the meeting.  Attendees could feel that these cell-based therapies are on the verge of becoming a valid treatment option for multiple age-related diseases, and that the future indeed promises improved healthspans for people worldwide.

From Kevin Perrott, PhD candidate
Campisi lab at the Buck Institute

The loss of “proliferative homeostasis” in a tissue, where cell replacement is out of balance in both quantity and proper cell type, is a common feature of many degenerative conditions associated with aging. This is why this symposium was such an important moment in the history of aging research.   Although the topic of stem cells has been a hot one for more than a decade, the field has been largely described in terms of its application to acute trauma, tissue engineering, and the diseases of the young.  These are all of course very important needs, but notable by its absence is the application of regenerative medicine to chronic degenerative disease, and the needs of a globally aging population are great and growing.   It is tremendous to see regenerative medicine targeted directly at the general phenomenon of aging and the underlying biological mechanisms which lead to many degenerative conditions.

The symposium presented an array of cutting-edge high-quality research focusing on the molecular and cellular mechanisms that affect the regenerative capacity of stem cells within the body with age, as well as how an aged environment in which the stem cells reside can equally affect that function.  All of the speakers were superb, highlighting new understandings in stem cell biology that will help lead to interventions and treatments for age-related degeneration.  From the pivotal role of the exploding field of RNA biology to engineering stem cells to treat diseases such as Huntington’s and Parkinson’s as well as Chronic Obstructive Pulmonary Disease, all the speakers focused on the critical application of regenerative medicine to degenerative disease.

Aging research has certainly “come of age” as we see it addressing some of the fundamental changes in stem cells that underlies the loss of tissue integrity that occurs with aging.  New details of the biology of aging uncovered by decades of basic research enables the field of biomedical gerontology to incorporate the biology of stem cells into its larger paradigm, giving hope that we will not only be able to slow down the loss of function that occurs with age, but potentially reverse it, at least in some targeted ways that the research presented showed was possible.