On the Path to Thymic Rejuvenation

The immune system declines with age in part because it is limited in the number of cells it can support, and too many of those cells become specialized memory cells over time, unable to contribute to the fight against new pathogens. A variety of approaches might be developed to address this issue: remove the excess memory cells, generate new immune cells from stem cells and regularly infuse them into the patient, or cause the body to start producing more new immune cells than it otherwise would.

Immune cells are created in the thymus, an organ which atrophies and diminishes its output of cells quite early in life: its evolved job is to generate an effective immune system in youth, not to keep pumping out immune cells at a high pace throughout life. Rejuvenation of the thymus to youthful activity is thus a way to boost native immune cell production, and some work in this direction is funded by the SENS Research Foundation:

SENS Research Foundation has made substantial investments in research on regenerative therapies for the aging immune system, with the aim of maintaining and restoring youthful immune function throughout life, eliminating the disparate burden of morbidity and mortality from infectious disease that falls disproportionately persons over the age of 60. We have targeted research dollars toward developing rejuvenation biotechnologies to repair the two forms of aging damage that are the most widely accepted drivers of immunosenescence.

In the lab of Dr. Janko Nikolich-┼Żugich at the Arizona Center on Aging, we are funding a project testing the clearance of dysfunctional, "senescent" cytotoxic CD8+ T-cells - cells that exert suppressive effects on the expansion and response of other, functional T-cells. And at the Wake Forest Institute for Regenerative Medicine, SENS Research Foundation is supporting Dr. John Jackson's efforts to apply the decellularized scaffold tissue engineering technique to the engineering of a transplantable thymic neo-organ.

[Researchers have recently] derived functioning [thymic epithelial progenitor cells (TEP)] from [embryonic_stem_cells], and found a way to further develop TEP into [thymic tissue] capable of supporting the development of mature T-cells from T-lymphoid progenitor cells in vivo. The success of this new study is remarkable, not only for what the investigators achieved, but for what it suggests can be achieved when its relatively crude system of thymic epithelial cell derivation and transplantation is superseded by the engineeering of true thymic neo-organs, such as those that are in development in Dr. Jackson's SENS Research Foundation-funded lab at this writing.

Already, Dr. Jackson's lab team have succeeded in seeding epithelial cells onto decellularized mouse thymus scaffolds, and they are now in the process of completing the initial characterization proliferation and coverage of these cells on the scaffolds. Soon, the reseeding procedure will be completed by seeding bone marrow stem cells purged of T-cells onto the epithelial-seeded scaffold. Once this is achieved, the production of mature T-cells by the bioengineered neo-organs will be evaluated. Advances already achieved in bioengineering other organs with decellularized scaffolds suggest a successful outcome; moreover, the thymus scaffold specifically provides the structural elements necessary for the cells that are grown on it to assume the complex microenvironmental relationships of a mature thymus.

Link: http://www.sens.org/research/research-blog/first-glimpse-thymic-rejuvenation

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