Innovita Research Foundation

I.R.F. / Aging news / Diseases / 10012901

Limbal Stem Cells, Immune Regulators and Novel Therapeutic Players
Posted on: January 29, 2010

Stem cells have been demonstrated in nearly all adult mammalian tissues and play a vital role in their physiological renewal and healing after injury. Due to their irreplaceable role in tissue repair, these cells had to develop mechanisms protecting them from deleterious inflammatory immune reactions and ensuring their increased resistance to various apoptosis-inducing agents.

Scientists have demonstrated that a population of mouse limbal cells highly enriched for cells expressing markers and charateristics of limbal stem cells (LSCs) suppresses in a dose-dependent manner the proliferation of lymphocytes elicited by mitogens or TCR-triggering and significantly inhibits the production of proinflammatory cytokines by activated T cells. The suppression was mediated by soluble factor(s) and did not affect early cell activation. LSCs were even more suppressive than mesenchymal stem cells or natural regulatory T cells.

In addition, the cells expressing markers and characteristics of LSC had significantly higher levels of mRNA for Fas ligand and for the antiapoptotic molecules Mcl-1, XIAP, and surviving than other limbal cell populations. LSCs were also more resistant to staurosporin-induced apoptotic cell death and to cell-mediated cytotoxic reaction than other limbal cells.

Collectively, these results suggest that SC isolated from fresh adult limbal tissue possess immunomodulatory properties and inhibit proinflammatory immune reactions. Simultaneously, these cells express high levels of mRNA for antiapoptotic molecules, which can protect them against cell-mediated cytotoxic reactions and various apoptosis-inducing agents. [1]

Hypothetical scheme of limbal stem cell niche.
Hypothetical scheme of limbal stem cell niche.

Limbal epithelial stem cells (SC) are located at the limbal basal layer. In this epithelial level, there are several other cell types in the vicinity such as the immediate progeny, i.e., early transient amplifying cells (eTAC), melanocytes (M), and Langerhan's cells (LC). It remains to be determined whether these cell types act as niche cells. It is believed that eTAC will be destined for progeny production by differentiating into late TACs (lTAC) located at the corneal basal layer, then into suprabasal post-mitotic cells (PMC), and finally into superficial terminally differentiated cells (TDC).

The limbal basement membrane (BM) separating the epithelium from the underlying stroma has several unique components. The subjacent limbal stroma contains mesenchymal cells (MC), which may also serve as niche cells. Because the limbal stroma is highly innervated and vascularized, the respective role of nerves (N) and blood vessels (BV) in the niche remains to be defined. [2]

Sources:
1. Holan V, Pokorna K, Prochazkova J, Krulova M, Zajicova A.; Immunoregulatory Properties of Mouse Limbal Stem Cells.; J Immunol. 2010 Jan 11.;
2. http://www.nature.com/cr/journal/v17/n1/fig_tab/7310137f2.html.
< Previous |  Next >