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It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [18F]-Fluoro-2-deoxy-2-d-glucose (18F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18F-FDG accumulation and 18F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of 18F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the aged mice. The treated group showed lower 18F-FDG accumulation levels in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the aged mice than the untreated groups, whereas higher 18F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

Objectives Delta-like 1 homolog (DLK1) is a non-canonical Notch ligand known to be expressed in several cancers but whose role in lung cancer is not yet fully understood. We sought to confirm DLK1 expression in small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), and to examine DLK1’s clinical significance. Furthermore, we examined the possible utility of DLK1 as a novel target in radioimmunotherapy (RIT). Methods We retrospectively assessed the correlation between clinical features and DLK1 expression by immunohistochemistry in resected specimens from 112 patients with SCLC and 101 patients with NSCLC. Moreover, we performed cell and animal experiments, and examined the possibility of RIT targeting DLK1 in SCLC using iodine-125 (125I) -labeled anti-DLK1 antibody, knowing that 125I can be replaced with the alpha-particle-emitter astatine-211 (211At). Results In SCLC and NSCLC, 20.5 % (23/112) and 16.8 % (17/101) of patients (respectively) had DLK1-positive tumors. In NSCLC, DLK1 expression was associated with recurrence-free survival (P Conclusion A proportion of SCLC and NSCLC exhibits DLK1 expression. As a clinical feature, DLK1 expression could be a promising prognostic factor for recurrence in patients with resected NSCLC. In addition, DLK1 could serve as a new therapeutic target, including RIT, as suggested by our pilot study using a radiolabeled anti-DLK1 antibody in SCLC.

There are various diagnostic and therapeutic agents for prostate cancer using bombesin (BBN) derivatives, but astatine-211 (211At)-labeled BBN derivatives have yet to be studied. This study presented a preliminary evaluation of 211At-labeled BBN derivative. Several nonradioactive iodine-introduced BBN derivatives (IB-BBNs) with different linkers were synthesized and their binding affinities measured. Because IB-3 exhibited a comparable affinity to native BBN, [211At]AB-3 was synthesized and the radiochemical yields of [211At]AB-3 was 28.2 ± 2.4%, with a radiochemical purity of >90%. The stability studies and cell internalization/externalization experiments were performed. [211At]AB-3 was taken up by cells and internalized; however, radioactivity effluxed from cells over time. In addition, the biodistribution of [211At]AB-3, with and without excess amounts of BBN, were evaluated in PC-3 tumor-bearing mice. Despite poor stability in murine plasma, [211At]AB-3 accumulated in tumor tissue (4.05 ± 0.73%ID/g) in PC-3 tumor-bearing mice, which was inhibited by excess native BBN (2.56 ± 0.24%ID/g). Accumulated radioactivity in various organs is probably due to free 211At. Peptide degradation in murine plasma and radioactivity efflux from cells are areas of improvement. The development of 211At-labeled BBN derivatives requires modifying the BBN sequence and preventing deastatination.

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [18F]-Fluoro-2-deoxy-2-D-glucose (18F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in super-aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18F-FDG accumulation and 18F-FDG autoradiography with insulin loading in super-aged and young wild-type mice. In control groups, the levels of 18F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the super-aged mice. After insulin loading, the 18F-FDG accumulation levels showed negative changes in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the super-aged mice, whereas positive changes were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18F-FDG accumulation levels in some organs of the super-aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

It is important to determine the functional changes of organs that occur as a result of aging, the understanding of which may lead to the maintenance of a healthy life. Glucose metabolism in healthy bodies is one of the potential markers used to evaluate the changes of organ function. Thus, information about normal organ glucose metabolism may help to understand the functional changes of organs. [18F]-Fluoro-2-deoxy-2-d-glucose (18F-FDG), a glucose analog, has been used to measure glucose metabolism in various fields, such as basic medical research and drug discovery. However, glucose metabolism changes in aged animals have not yet been fully clarified. The aim of this study is to evaluate changes in glucose metabolism in organs and brain regions by measuring 18F-FDG accumulation and 18F-FDG autoradiography with insulin loading in aged and young wild-type mice. In the untreated groups, the levels of 18F-FDG accumulation in the blood, plasma, muscle, lungs, spleen, pancreas, testes, stomach, small intestine, kidneys, liver, brain, and brain regions, namely, the cortex, striatum, thalamus, and hippocampus, were all significantly higher in the aged mice. The treated group showed lower 18F-FDG accumulation levels in the pancreas and kidneys, as well as in the cortex, striatum, thalamus, and hippocampus in the aged mice than the untreated groups, whereas higher 18F-FDG accumulation levels were observed in those in the young mice. These results demonstrate that insulin loading decreases effect on 18F-FDG accumulation levels in some organs of the aged mice. Therefore, aging can increase insulin resistance and lead to systemic glucose metabolism dysfunction.

Background 211At is one of the ideal nuclides for targeted radionuclide therapies (TRTs). Meta-[211At]astatobenzylguanidine (211At-MABG) has been proposed for the treatment of pheochromocytoma. To effectively use these radiopharmaceuticals, dosimetry must be performed. It is important to determine the absorbed doses of free 211At and 211At-MABG to determine the organs that may be at risk when using TRTs. The aim of this study was to estimate human dosimetry from preclinical biodistribution of free 211At and 211At-MABG in various organs in normal mice. Methods Male C57BL/6 N mice were administered 0.13 MBq of free 211At or 0.20 MBq of 211At-MABG by tail-vein injection. The mice were sacrificed at 5 min, and at 1, 3, 6, and 24 h after the injection (n = 5 for each group). The percentage of injected activity per mass in organs and blood (%IA/g) was determined. The human absorbed doses of free 211At and 211At-MABG were calculated using the Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM) version 2.0 and IDAC-Dose 2.1. Results High uptake of free 211At was observed in the lungs, spleen, salivary glands, stomach, and thyroid. The absorbed doses of free 211At in the thyroid and several tissues were higher than those of 211At-MABG. The absorbed doses of 211At-MABG in the adrenal glands, heart wall, and liver were higher than those of free 211At. Conclusions The absorbed doses of 211At-MABG in organs expressing the norepinephrine transporter were higher than those of free 211At. In addition, the biodistribution of free 211At was different from that of 211At-MABG. The absorbed dose of free 211At may help predict the organs potentially at risk during TRTs using 211At-MABG due to deastatination.

Stroke is a leading cause of death and disability worldwide. Recently, secondary damage to the brain has been hypothesized as a key aggravating element in the ischemic cascade. However, the interaction between cerebral infarction and immune organs is not fully understood. In this study, we investigated changes in rat brain, spleen, thymus, mesenteric lymph node, and liver at 3, 7, and 13 days after transient middle cerebral artery occlusion (tMCAO) by immunohistochemistry.Rat models of stroke were made by tMCAO. Functional assessment was performed at 3 h and 1, 3, 5, 7, 9, 11, and 13 days after MCAO. Rat organs were harvested for 2,3,5-triphenyltetrazolium chloride staining and immunohistochemistry.The number of CD8αThe present results indicate that stroke is a systemic disease that, in addition to affecting the brain, also induces responses in immune organs. These results suggest that systemic treatment might be a good strategy for clinical stroke care.

To explore stem-cell-targeted radioimmunotherapy with α-particles in acute myelogenous leukemia (AML), pharmacokinetics and dosimetry of the 211At-labeled anti-C-X-C chemokine receptor type 4 monoclonal antibody (211At-CXCR4 mAb) were conducted using tumor xenografted mice. The biological half-life of 211At-CXCR4 mAb in blood was 15.0 h. The highest tumor uptake of 5.05%ID/g with the highest tumor-to-muscle ratio of 8.51 ± 6.14 was obtained at 6 h. Radiation dosimetry estimated with a human phantom showed absorbed doses of 0.512 mGy/MBq in the bone marrow, 0.287 mGy/MBq in the kidney, and 211At-CXCR4 mAb for AML appears possible and requires further therapeutic studies.

Additional file 1: Table S1. Biodistribution of free 211At and 211At-MABG in normal mouse.

Background Stroke is a leading cause of death and disability worldwide. Recently, brain secondary damage has been hypothesized to be a key aggravating element in an ischemic cascade. However, the interaction between cerebral infarction and immune organs has yet to be fully understood. In this study, we investigated the changes in the rat brain, spleen, thymus, mesenteric lymph node, and liver at 3, 7, and 13 days after transient middle cerebral artery occlusion (tMCAO) by immunohistochemistry. Material and methods Rat models of stroke were made by tMCAO. Functional assessment was performed 3 h, and 1, 3, 5, 7, 9, 11, and 13 days after MCAO. Rat organs were harvested for 2,3,5-triphenyltetrazolium chloride staining and Immunohistochemistry. Results The CD8α+ T cells was found to decrease in the spleen, thymus, mesenteric lymph node, and liver, whereas it increased in the brain. Those of Iba1+ and CD68+ macrophages were decreased in the spleen, thymus, and mesenteric lymph node, whereas they were elevated in the brain and liver. Ki67+ cells showed the same characteristics as macrophages, and increased numbers of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive apoptotic cells were found in the spleen, mesenteric lymph node, liver, and brain. Conclusions The present results demonstrated that stroke is a systemic disease, which not only affects the brain, but also induces responses of immune organs. On the basis of these results, a systemic treatment might be a good strategy for clinical stroke care.

Background Eribulin, an inhibitor of microtubule dynamics, shows antitumor potency against a variety of solid cancers through its antivascular activity and remodeling of tumor vasculature. 18F-Fluoromisonidazole (18F-FMISO) is the most widely used PET probe for imaging tumor hypoxia. In this study, we utilized 18F-FMISO to clarify the effects of eribulin on the tumor hypoxic condition in comparison with histological findings. Material and methods Mice bearing a human cancer cell xenograft were intraperitoneally administered a single dose of eribulin (0.3 or 1.0 mg/kg) or saline. Three days after the treatment, mice were injected with 18F-FMISO and pimonidazole (hypoxia marker for immunohistochemistry), and intertumoral 18F-FMISO accumulation levels and histological characteristics were determined. PET/CT was performed pre- and post-treatment with eribulin (0.3 mg/kg, i.p.). Results The 18F-FMISO accumulation levels and percent pimonidazole-positive hypoxic area were significantly lower, whereas the number of microvessels was higher in the tumors treated with eribulin. The PET/CT confirmed that 18F-FMISO distribution in the tumor was decreased after the eribulin treatment. Conclusions Using 18F-FMISO, we demonstrated the elimination of the tumor hypoxic condition by eribulin treatment, concomitantly with the increase in microvessel density. These findings indicate that PET imaging using 18F-FMISO may provide the possibility to detect the early treatment response in clinical patients undergoing eribulin treatment.

Currently, there is increasing interest in human bone marrow stromal cells (hBMSCs) as regeneration therapy against cerebral stroke. The aim of the present study was to evaluate the feasibility and validity of hBMSC cultures with allogeneic platelet lysates (PLs). Platelet concentrates (PC) were harvested from healthy volunteers and made into single donor-derived PL (sPL). The PL mixtures (mPL) were made from three different sPL. Some growth factors and platelet cell surface antigens were detected by enzyme-linked immunosorbent assay (ELISA). The hBMSCs cultured with 10% PL were analyzed for their proliferative potential, surface markers, and karyotypes. The cells were incubated with superparamagnetic iron oxide (SPIO) agents and injected into a pig brain. MRI and histological analysis were performed. Consequently, nine lots of sPL and three mPL were prepared. ELISA analysis showed that PL contained adequate growth factors and a particle of platelet surface antigens. Cell proliferation capacity of PLs was equivalent to or higher than that of fetal calf serum (FCS). No contradiction in cell surface markers and no chromosomal aberrations were found. The MRI detected the distribution of SPIO-labeled hBMSCs in the pig brain. In summary, the hBMSCs cultured with allogeneic PL are suitable for cell therapy against stroke.

Background The potential application of bone marrow stromal cell (BMSC) therapy in stroke has been anticipated due to its immunomodulatory effects. Recently, positron emission tomography (PET) with [18F]DPA-714, a translocator protein (TSPO) ligand, has become available for use as a neural inflammatory indicator. We aimed to evaluate the effects of BMSC administration after transient middle cerebral artery occlusion (MCAO) using [18F]DPA-714 PET. The BMSCs or vehicle were administered intravenously to rat MCAO models at 3 h after the insult. Neurological deficits, body weight, infarct volume, and histology were analyzed. [18F]DPA-714 PET was performed 3 and 10 days after MCAO. Results Rats had severe neurological deficits and body weight loss after MCAO. Cell administration ameliorated these effects as well as the infarct volume. Although weight loss occurred in the spleen and thymus, cell administration suppressed it. In both vehicle and BMSC groups, [18F]DPA-714 PET showed a high standardized uptake value (SUV) around the ischemic area 3 days after MCAO. Although SUV was increased further 10 days after MCAO in both groups, the increase was inhibited in the BMSC group, significantly. Histological analysis showed that an inflammatory reaction occurred in the lymphoid organs and brain after MCAO, which was suppressed in the BMSC group. Conclusions The present results suggest that BMSC therapy could be effective in ischemic stroke due to modulation of systemic inflammatory responses. The [18F]DPA-714 PET/CT system can accurately demonstrate brain inflammation and evaluate the BMSC therapeutic effect in an imaging context. It has great potential for clinical application.

The phosphodiesterase (PDE) 3 inhibitor cilostazol, used as an anti-platelet drug, reportedly can also ameliorate ischemic brain injury. Here, we investigated the effects of cilostazol in a permanent focal ischemia mice model. Male Balb/c mice were subjected to permanent middle cerebral artery occlusion. Mice were then treated with either cilostazol (10 or 20mg/kg) or vehicle administered at 30min and 24h post-ischemia, and infarct volumes were assessed at 48h post-ischemia. Mice treated with 20mg/kg of cilostazol or vehicle were sacrificed at 6h or 24h post-ischemia and immunohistochemistry was used for brain sections. Treatment with 20mg/kg of cilostazol significantly reduced infarct volumes to 70.1% of those with vehicle treatment. Immunohistochemistry results for 8-hydroxydeoxyguanosine (OHdG) expression showed that some neurons underwent oxidative stress around the ischemic boundary zone at 6h post-ischemia. Cilostazol treatment significantly reduced the percentage of 8-OHdG-positive neurons (65.8±33.5% with vehicle and 21.3±9.9% with cilostazol). Moreover, NADPH oxidase (NOX) 2-positive neurons were significantly reduced with cilostazol treatment. In contrast, immunohistochemistry results for phosphorylated cyclic-AMP response element binding protein (pCREB) showed that there were significantly more pCREB-positive neurons around the ischemic boundary zone of cilostazol-treated mice than in those of vehicle-treated mice at 24h post-ischemia. These results suggested that cilostazol might have multiple mechanisms of action to ameliorate ischemic tissue damage, by attenuating oxidative stress mediated by suppressing NOX2 expression by ischemic neurons and an anti-apoptotic effect mediated through the pCREB pathway.

Recently, bone marrow stromal cell (BMSC) therapy for stroke is expected due to the immunomodulation effect. Here, we use PET and other detecting method to investigate the inflammatory changes of brain and lymphoid organs in rat stroke model. In this study, F344 rats were used as transient MCAO models. One part of rats were serially monitored by small-animal PET/CT system with new neuroinflammatory ligand [ 18 F]DPA-714. The brains were removed and sliced subsequently for autoradiograph (ARG) and TTC staining. The rest of rats were sacrificed, their brains and lymphoid organs were taken out, weighed, stained, etc. In histology, cytotoxic T cell (CD8α), macrophage (Iba1 and CD68), apoptosis (TUNEL) and proliferation (ki67) antibodies were chosen and analyzed. PET and ARG represented high concentration in the ischemic area which had been confirmed by TTC. In body imaging, no significant change was found. With the increase of ischemic severity, the size of lymphoid organs have a significantly decrease as well as the body weight. Histological assay showed cd8α + and ki67 + cells decreased in the lymphoid organs and increased in brain. Besides macrophages and apoptosis cells increased all the time in liver, in other organs, the rate of cells reached peak and gradually decreased more or less. In summary, [ 18 F]DPA-714 PET has a great potential for evaluating brain damage. Inflammatory responses in brain and lymphoid organs are distinct after stroke. Based on these results, we will continue the study for evaluating immunomodulation effect of BMSC transplantation therapy.

Recently, both basic and clinical studies demonstrated that bone marrow stromal cell (BMSC) transplantation therapy can promote functional recovery of patients with CNS disorders. A non-invasive method for cell tracking using MRI and superparamagnetic iron oxide (SPIO)-based labeling agents has been applied to elucidate the behavior of transplanted cells. However, the long-term safety of SPIO-labeled BMSCs still remains unclear. The aim of this study was to investigate the short-, middle- and long-term safety of the SPIO-labeled allogeneic BMSC transplantation. For this purpose, BMSCs were isolated from transgenic rats expressing green fluorescent protein (GFP) and were labeled with SPIO. The Na/K ATPase pump inhibitor ouabain or vehicle was stereotactically injected into the right striatum of wild-type rats to induce a lacunar lesion (n = 22). Seven days after the insult, either BMSCs or SPIO solution were stereotactically injected into the left striatum. A 7.0-Tesla MRI was performed to serially monitor the behavior of BMSCs in the host brain. The animals were sacrificed after 7 days (n = 7), 6 weeks (n = 6) or 10 months (n = 9) after the transplantation. MRI demonstrated that BMSCs migrated to the damage area through the corpus callosum. Histological analysis showed that activated microglia were present around the bolus of donor cells 7 days after the allogeneic cell transplantation, although an immunosuppressive drug was administered. The SPIO-labeled BMSCs resided and started to proliferate around the route of the cell transplantation. Within 6 weeks, large numbers of SPIO-labeled BMSCs reached the lacunar infarction area from the transplantation region through the corpus callosum. Some SPIO nanoparticles were phagocytized by microglia. After 10 months, the number of SPIO-positive cells was lower compared with the 7-day and 6-week groups. There was no tumorigenesis or severe injury observed in any of the animals. These findings suggest that BMSCs are safe after cell transplantation for the treatment of stroke.

Background and purpose: Recent studies have elucidated that the bone marrow stromal cells (BMSCs) have therapeutic potential against stroke. Some clinical trials have been starting up in practice. We aimed to evolve the autologous BMSC transplantation for stroke into the next generation. Materials and methods: Human BMSCs were cultured with human platelet lysate (hPL) instead of fetal calf serum (FCS). They were labeled with superparamagnetic iron oxide (SPIO). Rat ischemic stroke models were made and 5x105 cells were injected into the ipsilateral striatum stereotactically 7 days post-insult. Behavioral analysis, MRI for cell tracking, (18)F-FDG PET, and (123)I-Iomazenil SPECT were performed. The animals were sacrificed 5 to 8 weeks post-transplantation and histological analysis was performed. Results: There was no difference in the surface markers and cell proliferation between hPL and FCS. Although rotarod test showed that motor function deteriorated in rats suffered from permanent MCAo, BMSC-hPL transplantation enhanced recovery of the motor function, significantly. MRI demonstrated that SPIO-BMSCs aggressively migrated towards the lesion. Moreover, (18)F-FDG PET and (123)I-Iomazenil SPECT showed that BMSC transplantation promoted recovery of the glucose utilization and the binding potential of iomazenil in the peri-infarct area, respectively. Histological analysis supported the findings on MRI and showed the inclination for neural differentiation of donor cells. Conclusion: The hPL may be valuable and safe in expanding BMSCs. The application of bio-imaging techniques is also valuable for BMSC transplantation for stroke. Now we prepare the novel clinical trial against stroke, Research on Advanced Intervention using Novel Bone marrOW stem cell (RAINBOW) study. The present results are translated into the optimal design of the trial.

It has been reported that phosphodiesterase (PDE) 3 inhibitor cilostazol, which is used as an antiplatelet drug, could ameliorate ischemic brain injury. We aimed to investigate how cilostazol affected permanent focal ischemia. Male Balb/c mice were subjected to permanent middle cerebral artery occlusion. They were treated with cilostazol (10- mg/kg or 20-mg/kg) or vehicle 30 min and 24 h post-ischemia, and the infarct volume was assessed 48 h post-ischemia. The animals treated with 20-mg/kg cilostazol or vehicle were sacrificed 6 h or 24 h post-ischemia, and then the immunohistochemistry was performed to the brain sections. We demonstrated that the treatment with 20- mg/kg cilostazol significantly reduced infarct volume (70.1% vs. vehicle group). Immunohistochemistry against 8-hydroxydeoxyguanosine (OHdG) showed that some neurons suffered from oxidative stress in peri-infarct 6 h post-ischemia. The treatment with cilostazol reduced the number of 8-OHdG-positive neurons significantly (65.8 ± 33.5% in vehicle group and 21.3 ± 9.9% in cilostazol group). Moreover, the number of NADPH oxidase (NOX) 2-positive neurons was also reduced significantly (57.0 ± 13.6% in vehicle group and 26.5 ± 16.7% in cilostazol group). On the other hand, immunohistochemistry against phosphorylated cyclic-AMP response element binding protein (pCREB) showed that the number of the pCREB-positive neurons in peri-infarct of the cilostazol-treated animals was significantly higher than in vehicle-treated ones 24 h post-ischemia. These findings suggested that cilostazol could have multi-mechanisms to ameliorate the tissue damage, one was to attenuate oxidative stress by suppressing NOX2 on ischemic neurons, and another was anti-apoptotic effect through the pathway of Akt/pCREB.

Recently, both basic and clinical studies demonstrated that bone marrow stromal cell (BMSC) transplantation therapy can promote functional recovery of patients with CNS disorders. A non-invasive method for cell tracking using MRI and superparamagnetic iron oxide (SPIO)-based labeling agents has been applied to elucidate the behavior of transplanted cells. However, the long-term safety of SPIO-labeled BMSCs still remains unclear. The aim of this study was to investigate the short-, middle- and long-term safety of the SPIO-labeled allogeneic BMSC transplantation. For this purpose, BMSCs were isolated from transgenic rats expressing green fluorescent protein (GFP) and were labeled with SPIO. The Na/K ATPase pump inhibitor ouabain or vehicle was stereotactically injected into the right striatum of wild-type rats to induce a lacunar lesion (n = 22). Seven days after the insult, either BMSCs or SPIO solution were stereotactically injected into the left striatum. A 7.0-Tesla MRI was performed to serially monitor the behavior of BMSCs in the host brain. The animals were sacrificed after 7 days (n = 7), 6 weeks (n = 6) or 10 months (n = 9) after the transplantation. MRI demonstrated that BMSCs migrated to the damage area through the corpus callosum. Histological analysis showed that activated microglia were present around the bolus of donor cells 7 days after the allogeneic cell transplantation, although an immunosuppressive drug was administered. The SPIO-labeled BMSCs resided and started to proliferate around the route of the cell transplantation. Within 6 weeks, large numbers of SPIO-labeled BMSCs reached the lacunar infarction area from the transplantation region through the corpus callosum. Some SPIO nanoparticles were phagocytized by microglia. After 10 months, the number of SPIO-positive cells was lower compared with the 7-day and 6-week groups. There was no tumorigenesis or severe injury observed in any of the animals. These findings suggest that BMSCs are safe after cell transplantation for the treatment of stroke.

Let be an nonsingular matrix. In image processing, we must solve a system of linear equations[1], however, the solving of the System can be transformed to the solving of the equations . In this paper, we study the Hermitian positive definite solutions of the matrix equation . We give an equivalent equation of when the matrix equation has a Hermitian positive definite solution.