Steps Towards a Tissue Engineered Thymus

The thymus helps to generate the cell populations of your immune system when young, but it atrophies - a process called involution - quite early in adult life. Many of the frailties of aging have their roots in the age-related decline of the immune system. It fails with age in large part because it is a size-limited population of cells, and ever more of those cells become inappropriately configured and unable to respond to new threats. One of the proposed methods for dealing with this issue is to restore the thymus, and therefore create a stream of new immune cells to take up the slack. Transplanting a thymus from a young mouse into an old mouse improves the immune system and extends life, for example.

For human medicine, the focus is on finding ways to tissue engineer a new thymus from the patient's own cells, or spur regrowth of the existing involuted thymus. Here is an example of progress in the research and development needed for thymic tissue engineering - if you want to build a thymus, you first have to be able to reliably generate large numbers of the right sort of cells. Work on that goal is still in progress:

Thymus transplantation has great clinical potential for treating immunological disorders, but the shortage of transplant donors limits the progress of this therapy. Human embryonic stem cells (hESCs) are promising cell sources for generating thymic epithelial cells. Here, we report a stepwise protocol to direct the differentiation of hESCs into thymic epithelial progenitor-like cells (TEPLCs) by mimicking thymus organogenesis with sequential regulation of Activin, retinoic acid, BMP, and WNT signals.

The hESC-derived TEPLCs expressed the key thymic marker gene FOXN1 and could further develop in vivo into thymic epithelium expressing the functional thymic markers MHC II and AIRE upon transplantation. Moreover, the TEPLC-derived thymic epithelium could support mouse thymopoiesis in T-cell-deficient mice and promote human T cell generation in NOD/SCID mice engrafted with human hematopoietic stem cells (hHSCs). These findings could facilitate hESC-based replacement therapy and provide a valuable in vitro platform for studying human thymus organogenesis and regeneration.

Link: http://dx.doi.org/10.1016/j.stem.2013.06.014


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