Immunological Properties of Extraembryonic Human Mesenchymal Stromal Cells Derived from Gestational Tissue

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.

Section: Discussionmentioning

confidence: 99%

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

Trapani

Bassi²,

Fontana³

et al. 2015

“…The therapeutic properties of MSCs may vary substantially depending on their origin (1)(2)(3)(4)(5). Few data are available on clinical experience with MSCs from bone marrow (BM) or from other sources in similar patient groups.…”

Section: Introductionmentioning

confidence: 99%

“…decidua) and umbilical cord (UC) matrix (e.g. Wharton's jelly) are easily accessible without adverse donor site morbidity (2,3). Large quantities of potent "young" cells with high proliferative capacity can be obtained after short ex vivo expansion.…”

Section: Introductionmentioning

confidence: 99%

Different Procoagulant Activity of Therapeutic Mesenchymal Stromal Cells Derived from Bone Marrow and Placental Decidua

Moll

Ignatowicz

Catar

et al. 2015

109

While therapeutic mesenchymal stromal/stem cells (MSCs) have usually been obtained from bone marrow, perinatal tissues have emerged as promising new sources of cells for stromal cell therapy. In this study, we present a first safety follow-up on our clinical experience with placenta-derived decidual stromal cells (DSCs), used as supportive immunomodulatory and regenerative therapy for patients with severe complications after allogeneic hematopoietic stem cell transplantation (HSCT). We found that DSCs are smaller, almost half the volume of MSCs, which may favor microvascular passage. DSCs also show different hemocompatibility, with increased triggering of the clotting cascade after exposure to human blood and plasma in vitro. After infusion of DSCs in HSCT patients, we observed a weak activation of the fibrinolytic system, but the other blood activation markers remained stable, excluding major adverse events. Expression profiling identified differential levels of key factors implicated in regulation of hemostasis, such as a lack of prostacyclin synthase and increased tissue factor expression in DSCs, suggesting that these cells have intrinsic blood-activating properties. The stronger triggering of the clotting cascade by DSCs could be antagonized by optimizing the cell graft reconstitution before infusion, for example, by use of low-dose heparin anticoagulant in the cell infusion buffer. We conclude that DSCs are smaller and have stronger hemostatic properties than MSCs, thus triggering stronger activation of the clotting system, which can be antagonized by optimizing the cell graft preparation before infusion. Our results highlight the importance of hemocompatibility safety testing for every novel cell therapy product before clinical use, when applied using systemic delivery.

“…Another unique feature of CBMSCs is their low immunogenicity, which makes them suitable for allogenic cell therapies [14][15][16].…”

mentioning

confidence: 99%

Dissection of the Cord Blood Stromal Component Reveals Predictive Parameters for Culture Outcome

Barilani

Lavazza

Viganò

et al. 2015

In regenerative medicine, human cord blood-derived multipotent mesenchymal stromal cells (CBMSCs) stand out for their biological peculiarities demonstrated in in vitro and in vivo preclinical studies. Here, we present our 9-year experience for the consistent isolation of CBMSCs. Although nearly one CB unit out of two retains the potential to give rise to MSC colonies, only 46% of them can be cultured till low passages (P ‡ 4), but onefourth of those reaches even higher passages (P ‡ 8). Subsequent characterization for morphological, clonal, differentiation, and proliferation properties revealed two divergent CBMSC behaviors. In particular, a cumulative population doublings cut-off (CPD = 15) was identified that undoubtedly distinguishes two growth curves, and different degrees of commitment toward osteogenesis were observed. These data clearly show the existence of at least two distinct CBMSC subsets: one mainly short-living and less proliferative (SL-CBMSCs), the other long-living, with higher growth rate, and, very importantly, with significantly (P £ 0.01) longer telomere (LLCBMSCs). Moreover, significant differences in the immunoprofile before seeding were found among CB units giving rise to LL-CBMSCs or SL-CBMSCs or showing no colony formation. Finally, all the aforementioned results provided a peculiar and useful set of parameters potentially predictive for CBMSC culture outcome.