Immune Regulatory Properties of CD117^pos Amniotic Fluid Stem Cells Vary According to Gestational Age

Abstract

Amniotic Fluid Stem (AFS) cells are broadly multipotent fetal stem cells derived from the positive selection and ex vivo expansion of amniotic fluid CD117/c-kit pos cells. Considering the differentiation potential in vitro toward cell lineages belonging to the three germ layers, AFS cells have raised great interest as a new therapeutic tool, but their immune properties still need to be assessed. We analyzed the in vitro immunological properties of AFS cells from different gestational age in coculture with T, B, and natural killer (NK) cells. Nonactivated (resting) first trimester-AFS cells showed lower expression of HLA class-I molecules and NK-activating ligands than second and third trimester-AFS cells, whose features were associated with lower sensitivity to NK cell-mediated lysis. Nevertheless, inflammatory priming with interferon gamma (IFN-g) and tumor necrosis factor alpha (TNF-a) enhanced resistance of all AFS cell types to NK cytotoxicity. AFS cells modulated lymphocyte proliferation in a different manner according to gestational age: first trimester-AFS cells significantly inhibited T and NK cell proliferation, while second and third trimester-AFS cells were less efficient. In addition, only inflammatory-primed second trimester-AFS cells could suppress B cell proliferation, which was not affected by the first and third trimester-AFS cells. Indolamine 2,3 dioxygenase pathway was significantly involved only in T cell suppression mediated by second and third trimester-AFS cells. Overall, this study shows a number of significant quantitative differences among AFS cells of different gestational age that have to be considered in view of their clinical application.

Counteracting bone fragility with human amniotic mesenchymal stem cells

“…AFSCs are attractive candidates for cell therapy because they are easily accessible during pregnancy from the surplus of amniocentesis samples and can be used without ethical restriction9101112. They also have a high expansion potential, are non-tumorigenic, tolerogenic, anti-inflammatory and are small enough to pass through capillary beds to reach distant sites of action13141516. Their immunological properties make it possible to use them as universal allogeneic donor13141516.…”

“…They also have a high expansion potential, are non-tumorigenic, tolerogenic, anti-inflammatory and are small enough to pass through capillary beds to reach distant sites of action13141516. Their immunological properties make it possible to use them as universal allogeneic donor13141516. Compared to their adult counterparts, fetal MSCs have longer telomeres, have accumulated fewer genetic mutations and are easier to reprogram to pluripotency4.…”

The immunomodulatory function of human amniotic fluid stromal cells on B lymphocytes

“…Many neural system autoimmune disorders like myasthenia gravis, neuromyelitis optic spectrum disease, guillain-barre are mainly caused by humoral immune disfunction. Several studies have showed hAFSCs can modulate T cell function under certain condition [4,17,18], but few has been learnt about their effect on B cells. Even few has been learnt about MSCs immunomodulating effect on B cells.…”

Translating amniotic fluid-derived stem cells for transplantation in stroke

“…A recent in vitro investigation determined the gestational age (i.e., those derived from first-, second-to thirdtrimester) that influence AFSCs' function in regulating the proliferation of lymphocytes [10]. Interestingly, firsttrimester AFSCs considerably hindered natural killer cell and T cell proliferation, while second-and thirdtrimester AFSCs were far less effective and only the inflammatory-primed second-trimester AFSCs could restrict B-cell proliferation [10].…”