The Effect of Tissue Preparation and Donor Age on Striatal Graft Morphology in the Mouse

Huntington's disease (HD) is a progressive neurodegenerative disease in which striatal medium spiny neurons (MSNs) are lost. Neuronal replacement therapies aim to replace MSNs through striatal transplantation of donor MSN progenitors, which successfully improve HD-like deficits in rat HD models and have provided functional improvement in patients. Transplants in mouse models of HD are more variable and have lower cell survival than equivalent rat grafts, yet mice constitute the majority of transgenic HD models. Improving the quality and consistency of mouse transplants would open up access to this wider range of rodent models and facilitate research to increase understanding of graft mechanisms, which is essential to progress transplantation as a therapy for HD. Here we determined how donor age, cell preparation, and donor/host strain choice influenced the quality of primary embryonic grafts in quinolinic acid lesion mouse models of HD. Both a within-strain (W-S) and a between-strain (B-S) donor/host paradigm were used to compare transplants of donor tissues derived from mice at embryonic day E12 and E14 prepared either as dissociated suspensions or as minimally manipulated tissue pieces (TP). Good graft survival was observed, although graft volume and cellular composition were highly variable. The effect of cell preparation on grafts differed significantly depending on donor age, with E14 cell suspensions yielding larger grafts compared to TP. Conversely, TP were more effective when derived from E12 donor tissue. A W-S model produced larger grafts with greater MSN content, and while high levels of activated microglia were observed across all groups, a greater number was found in B-S transplants. In summary, we show that the effect of tissue preparation on graft morphology is contingent on the age of donor tissue used. The presence of microglial activation in all groups highlights the host immune response as an important consideration in mouse transplantation.

A sulfonated polymer membrane with Ag-based graft: morphology, characterization, antimicrobial activity and interception ability

Ag-based nano-graft can impart broad-spectrum antimicrobial activity to a polymer membrane and enhance its anti-fouling capacity effectively.

PU.1-Silenced Dendritic Cells Induce Mixed Chimerism and Alleviate Intestinal Transplant Rejection in Rats via a Th1 to Th2 Shift

Background/Aims: Intestinal transplantation is an effective treatment for end-stage bowel failure; however, graft rejection and the toxicity associated with non-specific immunosuppression are major limitations of this procedure. Studies have shown that mixed chimerism can produce post-transplantation immune tolerance. Here, we demonstrate that in rat intestinal transplantation, PU.1-silenced dendritic cells (DCs) plus bone marrow (BM) cell transfusion results in mixed chimerism, and we investigate the mechanisms responsible for the effects of mixed chimerism rejection. Methods: In a model of intestinal transplantation, male Brown Norway rats were the donors, and female Lewis rats were the recipients that were randomly divided into 4 groups: control, BM, BM-imDCs and BM-PU.1. The dynamic changes in graft morphology, rejection scoring and serum concentrations of Th1/Th2-related cytokines were investigated on postoperative days 0, 7, 14, 21, and 30. Results: The BM-PU.1 group had better graft health, milder pathologic injuries, and lower rejection grades compared with the other groups. The rates of mixed chimerism were significantly highest in the BM-PU.1 group and correlated with decreases in serum IL-2 and increases in serum IL-10. Conclusion: Transfusion of PU.1-silenced DCs and BM cells induces stable mixed chimerism and has the potential to reduce pathologic injuries via a pro-Th2 shift in the Th1/Th2 balance.

Effect of Fluorometholone/Tetrahydrozoline Fixed Combination on Conjunctival Autograft Morphology after Primary Pterygium Excision

Purpose.To evaluate the effect of a fluorometholone/tetrahydrozoline fixed combination on conjunctival graft morphology after primary pterygium excision.Methods.The patients who underwent pterygium excision with conjunctival autograft transplantation were randomized into three groups based on postoperative medications as the fluorometholone/tetrahydrozoline group, fluorometholone group, and dexamethasone group. Conjunctival graft thickness was measured with anterior segment optical coherence tomography. The conjunctival graft hyperemia was evaluated using a high definition external camera.Results.The mean graft thickness was significantly lower in the fluorometholone/tetrahydrozoline group compared with fluorometholone and dexamethasone groups at 2 weeks (P=0.002andP=0.012, resp.) and at 1 month after surgery (P=0.003andP=0.013, resp.). The conjunctival hyperemia score was significantly lower in the fluorometholone/tetrahydrozoline group compared with fluorometholone and dexamethasone groups at 2 weeks (P=0.000andP=0.000, resp.) and at 1 month (P=0.039andP=0.040, resp.). The graft thickness and conjunctival hyperemia score were similar among the groups at 1 week and 3 months (P>0.05).Conclusion.The findings of the present study revealed that treatment with the fluorometholone/tetrahydrozoline fixed combination may be helpful to decrease graft edema and to achieve better cosmetic appearance at 2 weeks and 1 month after pterygium excision.