Administration Of Autologous Mononuclear Cells Research Articles

Outcomes of IVF programs with intrauterine administration of autologous mononuclear cells in women with repeated implantation failure

Frequency of the repeated implantation failure (RIF) in assisted reproductive technology programs remains to be high, reaching 50-75%. Intrauterine administration of autologous mononuclear cells before embryo transfer is a technique for the RIF immunocorrection being used in assisted reproductive technology programs. Direct effect of mononuclear cells upon implantation was first studied in 2006 and showed that intrauterine administration of autologous mononuclear cells prior to embryo transfer proved to significantly increase implantation frequency, as well as incidence of clinical pregnancy, and frequency of delivery in the patients with a history of RIF. The aim of this study was to evaluate the effect of intrauterine administration of autologous peripheral blood mononuclear cells prior to embryo transfer upon the results of assisted reproductive technology programs in women with a history of RIF, and to evaluate cytokine profile of the supernates from the injected cultures of peripheral blood mononuclear cells.The study included 129 women with RIF included into the assisted reproductive technology programs. The patients were divided into three groups with intrauterine administration before embryo transfer in a stimulated cycle and in a cryocycle: group 1, treated with mononuclear cells activated by human chorionic gonadotropin; group 2, with mononuclear cells without activation by human chorionic gonadotropin; group 3 who received saline solution (placebo). Clinical and anamnestic data of the women from these groups did not differ. The age of women in all three groups was also similar. The number of RIFs in their anamnesis was comparable for the 3 groups. Analysis of the embryological parameters also showed that there were no significant differences in the number of transferred embryos, including those of good quality.The levels of IL-2 (p = 0.006), IL-4 (p = 0.012), IL-5 (p = 0.012), IL-12p70 (p = 0.011), IFNγ (p = 0.012), GM-CSF (p = 0.026), and TNFα (p = 0.021) were found to be higher in the supernatants of human chorionic gonadotropin-activated mononuclear cells of women with advanced cryocycle implantation, than in supernatants of inactivated chorionic gonadotropin mononuclear cells. Frequencies of implantation and clinical pregnancy were significantly higher in the groups with intrauterine administration of autologous mononuclear cells, both in stimulated cycle and the cryocycle compared to the placebo groups.The cytokine profile of the mononuclear cell culture supernates upon intrauterine administration affects the efficiency of assisted reproductive technology programs in the women with RIF. Hence, the data obtained may allow us to develop a personalized approach to usage of various immunotherapies in assisted reproductive technology programs for the patients with a history of repeated implantation failure.

Abstract W P94: Autologous Bone Marrow Derived Mononuclear Cells Attenuate Cerebral Edema and Inflammation in Intracerebral Hemorrhage

Background: Autologous bone marrow derived mononuclear cells (MNCs) improve functional recovery after ischemic stroke in rodent models. We now investigate the therapeutic effects of MNCs in intracerebral hemorrhage (ICH) and explore if MNCs impact the post-ICH inflammatory response. Methods: ICH was induced by stereotaxic infusion of 70 ul autologous whole blood into the left striatum in young male Long Evans rats. At 24 hrs after ICH, rats were randomized to receive an intravenous administration of autologous MNCs (10 million cell/kg) or saline. MNCs were isolated from the bone marrow harvest of the tibias at 22 hrs after ICH without causing limb impairment. A separate sham control group underwent the same surgical procedures but without the blood injection and the aspiration of bone marrow. At 3 days after randomization, brains were harvested to measure cerebral edema and various markers of inflammation in the perihematomal area. Results: Compared to the saline treated controls, MNCs significantly decreased brain water content in the ipsilateral hemisphere (p < 0.05, n = 3 in each group; Fig. 1). MNCs significantly reduced the number of neurotrophils and iNOS-positive microglia in the perihematomal area compared with saline-treated animals (P < 0.05, n = 3 in each group; Fig. 2). Moreover, MNCs reduced the expression of high-mobility group protein box-1 (HMGB1), S100β, matrix metalloproteinase 9 (MMP9), and aquaporin 4 (AQP4) in the perihematomal area compared with saline-treated animals (P < 0.05, n = 3 in each group; Fig. 3). Conclusions: We demonstrate for the first time that intravenously transplanted autologous MNCs can ameliorate brain edema and modulate the inflammatory responses after ICH. This is the first study to perform a bone marrow harvest and autologous infusion of MNCs after ICH. Functional behavioral tests are underway to assess the long-term effects of MNCs as a potential treatment for ICH.

A therapeutic window for intravenous administration of autologous bone marrow after cerebral ischemia in adult rats

The primary objective of this study was to test the hypothesis that intravenous administration of autologous bone marrow cells could improve functional recovery after middle cerebral artery occlusion (MCAO) for 45 min in the rat and to determine specific time windows for efficacy. Mononuclear cells from autologous bone marrow were transfected with the LacZ reporter gene, and injected intravenously into rats at 3–72 h after induction of MCAO. Histological analysis of the ischemic lesion at 14 days after transplantation revealed reduced ischemic lesion volume. Lesion volume was 250±45 mm 3 ( n=6) after MCAO without cell transplantation. Lesions were minimally detected by absence of 2,3,5-triphenyltetrazolium chloride (TTC) staining when bone marrow cells were infused 3 h after lesion induction. Lesions were clearly detected beginning with the 6-h postlesion group and became progressively larger at 12, 24 and 72 h (80±25, 140±18, and 180±22 mm 3, respectively; n=6 for each group). Transplanted LacZ + bone marrow cells accumulated extensively in and around the ischemic lesions, and immunohistochemistry suggests some neuronal and glial lineage differentiation. Behavioral testing (Morris water maze and Treadmill stress test) indicated greater functional recovery in the treated group. These findings suggest that early intervention with intravenous administration of autologous mononuclear cells from bone marrow can reduce lesion size in the MCAO model in the rat, and improve functional outcome.