Brain-derived neurotrophical factor after olfactory ensheathing cells transplantation in spinal cord injury of rats

Objective To observe the expression of brain - derived neurotrophical factor ( BDNF) in injury spinal cord after transplantation olfactory ensheathing cells ( OECs) , and to investigate the mechanism of OECs repairing spinal cord injury. Methods OECs from GFP transgenic rats were separated and cultured for transplantation. Spinal cord injury rats were separated two groups by

Nogo-A expression in injured spinal cord following human olfactory mucosa-derived olfactory ensheathing cells transplantation

Transplantation of olfactory bulb-derived olfactory ensheathing cells （OECs） promotes motor functional recovery in rats with acute spinal cord injury, possibly by Nogo-A expression changes at the injury site. The present study transplanted OECs derived from the olfactory mucosa （OM） of rats OM-derived OEC （OM-OEC） transplantation significantly reduced the increase of Nogo-A protein and mRNA expression caused by spinal cord injury, supporting the hypothesis that OM-OECs improve spinal cord regeneration by reducing Nogo-A expression.

Transplantation of fibrin-thrombin encapsulated human induced neural stem cells promotes functional recovery of spinal cord injury rats through modulation of the microenvironment

Recent studies have mostly focused on engraftment of cells at the lesioned spinal cord,with the expectation that differentiated neurons facilitate recovery.Only a few studies have attempted to use transplanted cells and/or biomaterials as major modulators of the spinal cord injury microenvironment.Here,we aimed to investigate the role of microenvironment modulation by cell graft on functional recovery after spinal cord injury.Induced neural stem cells reprogrammed from human peripheral blood mononuclear cells,and/or thrombin plus fibrinogen,were transplanted into the lesion site of an immunosuppressed rat spinal cord injury model.Basso,Beattie and Bresnahan score,electrophysiological function,and immunofluorescence/histological analyses showed that transplantation facilitates motor and electrophysiological function,reduces lesion volume,and promotes axonal neurofilament expression at the lesion core.Examination of the graft and niche components revealed that although the graft only survived for a relatively short period(up to 15 days),it still had a crucial impact on the microenvironment.Altogether,induced neural stem cells and human fibrin reduced the number of infiltrated immune cells,biased microglia towards a regenerative M2 phenotype,and changed the cytokine expression profile at the lesion site.Graft-induced changes of the microenvironment during the acute and subacute stages might have disrupted the inflammatory cascade chain reactions,which may have exerted a long-term impact on the functional recovery of spinal cord injury rats.

Advances in the treatment of autism spectrum disorder:Wharton jelly mesenchymal stem cell transplantation

BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental disorder with multifaceted origins.In recent studies,neuroinflammation and immune dysregulation have come to the forefront in its pathogenesis.There are studies suggesting that stem cell therapy may be effective in the treatment of ASD.AIM To evolve the landscape of ASD treatment,focusing on the potential benefits and safety of stem cell transplantation.METHODS A detailed case report is presented,displaying the positive outcomes observed in a child who underwent intrathecal and intravenous Wharton’s jelly-derived mesenchymal stem cells(WJ-MSCs)transplantation combined with neurorehabilitation.RESULTS The study demonstrates a significant improvement in the child’s functional outcomes(Childhood Autism Rating Scale,Denver 2 Developmental Screening Test),especially in language and gross motor skills.No serious side effects were encountered during the 2-year follow-up.CONCLUSION The findings support the safety and effectiveness of WJ-MSC transplantation in managing ASD.

Treatment of spinal cord injury by transplantation of cells via cerebrospinal fluid

It is very important to probe into the axonal regeneration and functional recovery of central nervous system （CNS） after implantation of cells into cerebrospinal fluid （CSF） for spinal cord injury （SCI）. Transplantation of cells via CSF poses great potentials for SCI in clinic. Studies on administration of cells via CSF indicate that the method is safe and convenient. The method is more suitable to treating multiple lesions of the CNS since it does not produce open lesions. However, there are disputes over its promotion effects on axonal regeneration and functional recovery of spinal cord after injury; and some questions, such as the mechanisms of functional recovery of spinal cord, the proper time window of cell transplantation, and cell types of transplantation, still need to be handled. This review summarized the method of cell transplantation via CSF for treatment of SCI.

Effect of intracoronary autologous bone marrow mononuclear cells transplantation on arrhythmia in canines

Objective To observe the survival and the differentiation of grafted bone marrow cells(BM-MNCs)in host myocardium.To observe whether BM-MNCs transplantation can potentially cause arrhythmia and whether the BM-MNCs transplantation can alter the spatial distribution of connexins,important mediator for arrhythmia gen-

Bone Marrow Stromal Cells Express Neural Phenotypes in vitro and Migrate in Brain After Transplantation in vivo

Objective To investigate the differentiation of bone marrow stromal cells （BMSC） into neuron-like cells and to explore their potential use for neural transplantation. Methods BMSC from rats and adult humans were cultured in serum-containing media. Salvia miltiorrhiza was used to induce human BMSC （hBMSC） to differentiate. BMSC were identified with immunocytochemistry. Semi-quantitative RT-PCR was used to examine mRNA expression of neurofilamentl （NF1）, nestin and neuron-specific enolase （NSE） in rat BMSC （rBMSC）. Rat BMSC labelled by Hoschst33258 were transplanted into striatum of rats to trace migration and distribution. Results rBMSC expressed NSE, NFI and nestin mRNA, and NF1 mRNA and expression was increased with induction of Salvia miltiorrhiza. A small number of hBMSC were stained by anti-nestin, anti-GFAP and anti-S 100. Salvia miltiorrhiza could induce hBMSC to differentiate into neuron-like cells. Some differentiated neuron-like cells, that expressed NSE, beta-tubulin and NF-200, showed typical neuron morphology, but some neuron-like cells also expressed alpha smooth muscle protein, making their neuron identification complicated, rBMSC could migrate and adapted in the host brains after being transplanted. Conclusion Bone marrow stromal cells could express phenotypes of neurons, and Salvia milliorrhiza could induce hBMSC to differentiate into neuron-like cells, If BMSC could be converted into neurons instead of mesenchymal derivatives, they would be an abundant and accessible cellular source to treat a variety of neurological diseases.

Transplantation of endothelial progenitor cells transfected with VEGF165 to restore erectile function in diabetic rats

The present study investigated the effect of transplanting endothelial progenitor cells （EPCs） transfected with the vascular endothelial growth factor gene （VEGF165） into the corpora cavernosa of rats with diabetic erectile dysfunction （ED）. A rat model of diabetic ED was constructed via intraperitoneal injection of streptozotocin. After streptozotocin treatment, pre-treated EPCs from each of three groups of rats were transplanted into their corpora cavernosa. Our results, following intracavernosal pressure （ICP） monitoring, showed that ICP increased significantly among rats in the trial group when compared to the results from rats in the blank-plasmid and control groups during basal conditions and electrical stimulation （P〈O.01 for both comparisons）. Histological examination revealed extensive neovascularisation in the corpora cavernosa of rats in the trial group. Fluorescence microscopy indicated that many of the transplanted EPCs in the trial group survived, differentiated into endothelial cells and integrated into the sites of neovascularisation. Based on the results of this study, we conclude that transplantation of VEGF165-transfected EPCs into the corpora cavernosa of rats with diabetic ED restores erectile function.

Combined Transplantation of Neural Stem Cells and Olfactory Ensheathing Cells Improves the Motor Function of Rats with Intracerebral Hemorrhage

Objective To investigate the effects of combined transplantation of neural stem cells （NSC） and olfactory ensheathing cells （OEC） on the motor function of rats with intracerebral hemorrhage. Methods In three days after a rat model of caudate nucleus hemorrhage was established, NSCs and OEC, NSC, OEC （from embryos of Wistar rats） or normal saline were injected into bematomas of rats in combined transplantation group, NSC group, OEC group, and control group, respectively. Damage of neural function was scored before and in 3, 7, 14, 30 days after operation. Tissue after transplantation was observed by immunocytochemistry staining. Results The scores for the NSC, OEC and co-transplantation groups were significantly lower in 14 and 30 days after operation than in 3 days after operation （P〈0.05）. The scores for the NSC and OEC groups were significantly lower than those for the control group only in 30 days after operation （P〈0.05）, while the difference for the NSC-OEC group was significant in 14 days after operation （P〈0.05）. Immunocytochemistry staining revealed that the transplanted OEC and NSC could survive, migrate and differentiate into neurons, astrocytes, and oligodendrocytes. The number of neural precursor cells was greater in the NSC and combined transplantation groups than in the control group. The number of neurons differentiated from NSC was significantly greater in the co-transplantation group than in the NSC group. Conclusion Co-transplantation of NSC and OEC can promote the repair of injured tissue and improve the motor fimction of rats with intracerebral hemorrhage.

Transplantation of neurotrophin-3-transfected bone marrow mesenchymal stem cells for the repair of spinal cord injury

Bone marrow mesenchymal stem cell transplantation has been shown to be therapeutic in the repair of spinal cord injury. However, the low survival rate of transplanted bone marrow mesen- chymal stem cells in vivo remains a problem. Neurotrophin-3 promotes motor neuron survival and it is hypothesized that its transfection can enhance the therapeutic effect. We show that in vitro transfection of neurotrophin-3 gene increases the number of bone marrow mesenchymal stem cells in the region of spinal cord injury. These results indicate that neurotrophin-3 can promote the survival of bone marrow mesenchymal stem cells transplanted into the region of spinal cord injury and potentially enhance the therapeutic effect in the repair of spinal cord injury.

Assessment of left ventricular segmental function after autologous bone marrow stem cells transplantation in patients with acute myocardial infarction by tissue tracking and strain imaging

Background Emerging evidence suggests that stem cells can be used to improvecardiac function in patients after acute myocardial infarction. In this randomized trial, we aimedto use Doppler tissue tracking and strain imaging to assess left ventricular segmental functionafter intracoronary transfer of autologous bone-marrow stem cells ( BMCs) for 6 months' follow up.Methods Twenty patients with acute myocardial infarction and anterior descending coronary arteryocclusion proven by angiography were double-blindedly randomized into intracoronary injection ofbone-marrow cell (treated, n = 9 ) or diluted serum ( control, n = 11) groups. GE vivid 7 andQ-analyze software were used to perform echocardiogram in both groups 1 week, 3 months and 6 monthsafter treatment. Three apical views of tissue Doppler imaging were acquired to measure peak systolicdisplacement ( D_s) and peak systolic strain (ε_(peak)) from 12 segments of LV walls. Leftventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume ( ESV) wereobtained by Simposon's biplane method. Results (1) 3 months later, D_a and ε_(peak) over theinfract-related region clearly increased in the BMCs group [D_8: (4.49 ±2.71) mm vs (7.56 ±2.95)mm, P < 0. 01; ε_(peak): ( - 13.40 ±6.00)% vs ( - 17.06 ± 6.05)% , P<0.01] , but not in thecontrol group [ D_8: (4.74 ±2.67) mm vs (5.01 ±3.23) mm, P >0.05; ε_(peak): ( - 13.84 ± 6.05) %vs ( - 15.04 ± 6.75) % , P > 0.05 ]. At the same time, D_s over the normal region also increased,but the D_8 enhancement was markedly higher in the BMCs group than that in the control group [ (3.21±3.17) mm vs (0.76 ± 1.94) mm, P <0.01 ]. Parameters remained steady from the 3rd to 6th month ineither group (P >0.05). (2) LVEF in treated and control groups were almost the same at baseline (1st week after PCI) [ (53.37 ± 8.92) % vs (53.51 ± 5.84) % , P > 0.05 ]. But 6 months later, LVEFin the BMCs group were clearly higher than that in the control group [(59.33 ± 12.91)% vs (50.30 ±8.30)%, P < 0.05 ]. (3) There were no evident difference in EDV or ESV between two groups atbaseline [ EDV; (113.74 ±23.24) ml vs (129.94 ±32.72) ml , P>0.05; ESV: (57.12 ±18.66) ml vs(62.09 ± 17.68) ml, P > 0.05 ]. Three months later, EDV and ESV in the control group were markedlygreater than those in the BMCs group [EDV; (154.89 ±46.34) ml vs (104.85 ±33.21) ml, P<0.05; ESV:(82.91 ±35.79) ml vs (49.54 ± 23.32) ml, P < 0.05 ]. But EDV and ESV did not change much from 3rdto 6th month in either group (P>0.05). Conclusions Emergency transplantation of autologous BMCs inpatients with acute myocardial infarction helps to improve global and regional contractility andattenuate post-infarction left ventricular remodeling. Tissue tracking and strain imaging providequick, simple and noninvasive methods for quantifying left ventricular segmental function in humans.

Neural differentiation of human Wharton＇s jelly-derived mesenchymal stem cells improves the recovery of neurological function after transplantation in ischemic stroke rats

Human Wharton＇s jelly-derived mesenchymal stem cells（h WJ-MSCs）have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their application in the treatment of ischemic stroke,therefore their therapeutic effect requires further verification.In this study,h WJ-MSCs were transplanted into an ischemic stroke rat model via the tail vein 48 hours after transient middle cerebral artery occlusion.After 4 weeks,neurological functions of the rats implanted with h WJ-MSCs were significantly recovered.Furthermore,many h WJ-MSCs homed to the ischemic frontal cortex whereby they differentiated into neuron-like cells at this region.These results confirm that h WJ-MSCs transplanted into the ischemic stroke rat can differentiate into neuron-like cells to improve rat neurological function and behavior.

Monoamine alterations and rotational asymmetry in a rat model of Parkinson's disease following lateral ventricle transplantation of human amniotic epithelial cells

BACKGROUND： Human amniotic epithelial cells （HAECs） can differentiate into neurons, astrocytes and oligodendrocytes. They biologically secrete many active neurotrophins and have the capacity to metabolize dopamine enzymes. These features underlie a theoretical basis for the treatment of Parkinson＇s disease （PD）. OBJECTIVE： To investigate the survival and differentiation of transplanted HAECs in the lateral ventricle of PD model rats, and to explore its effect on circling behavior, as well as levels of dopamine （DA）, the metabolite homovanillic acid, dihydroxyphenyl acetic acid, 5-hydroxyindoleacetic acid, and 5-hydroxytryptamine in the striatum. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, and Shanghai Celstar Institute of Biotechnology from May 2007 to December 2008. MATERIALS： HAECs were derived from the placental chorion following caesarean delivery at the Shanghai International Matemal and Child Health Hospital. 6-hydroxydopamine （6-OHDA）, and mouse anti-human Vimentin monoclonal antibody were purchased from Sigma, USA; mouse anti-human nestin and tyrosine hydroxylase （TH） monoclonal antibodies were purchased from Chemicon, USA. METHODS： A total of 114 healthy, adult, Sprague Dawley rats were randomly assigned to two groups： PD model [n = 90, stereotactic microinjection of 2 μL 6-OHDA （3.5 μg/uL） into the striatum] and control （n = 24, no treatment）. The 51 successful PD model rats were randomly divided into 3 subgroups （n = 17）： HAEC, PBS, and model. The HAEC and PBS groups were respectively injected with 10 μL PBS solution containing 1 × 10^5/mL HAECs or 10 pL PBS into the lateral ventricle. The model group was not treated. MAIN OUTCOME MEASURES： TH protein expression in the striatum was evaluated by immunohistochemistry 5 weeks after HAEC transplantation. At 10 weeks, HAEC survival in the lateral ventricle was investigated by immunofluorescent staining; differentiation of HAECs in the lateral and third ventricles was examined by TH immunohistochemistry; concentrations of DA, homovanillic acid, dihydroxyphenyl acetic acid, 5-hydroxyindoleacetic acid, and 5-hydroxytryptamine in the striatum, as well as DA concentration in the cerebrospinal fluid, were measured with high-performance liquid chromatography-electrochemical detection. Circling behavior of PD model rats was consecutively observed for 10 weeks following intraperitoneal injection of amphetamine 1 week after successful model establishment. RESULTS： tn the HAEC group, the number of TH-positive cells significantly increased in the striatum, and circling behavior significantly decreased, compared with the PBS and model groups （P 〈 0.01）. In addition, monoamine concentrations in the striatum, as well as DA concentrations in the cerebrospinal fluid, significantly increased, compared with the PBS group （P 〈 0.05-0.01）. Moreover, a large number of nestin-, vimentin-, and TH-positive cells were observed in the lateral and third ventricles following HAEC injection.CONCLUSION： HAECs survived for 10 weeks with no overgrowth following transplantation into the lateral ventricle of PD model rats. Moreover, the cells differentiated into dopaminergic neurons, which increased DA secretion. HAEC transplantation improved cycling behavior in PD model rats.

Transplantation of autologous bone marrow-derived mesenchymal stem cells for traumatic brain injury

Results from the present study demonstrated that transplantation of autologous bone marrow-derived mesenchymal stem cells into the lesion site in rat brain significantly ameliorated brain tissue pathological changes and brain edema, attenuated glial cell proliferation, and increased brain-derived neurotrophic factor expression. In addition, the number of cells double-labeled for 5-bromodeoxyuridine/glial fibrillary acidic protein and cells expressing nestin increased. Finally, blood vessels were newly generated, and the rats exhibited improved motor and cognitive functions. These results suggested that transplantation of autologous bone marrow-derived mesenchymal stem cells promoted brain remodeling and improved neurological functions following traumatic brain injury.

Magnetically labeled mesenchymal stem cells after autologous transplantation into acutely injured liver

AIM:To evaluate tracking of magnetically labeled mesenchymal stem cells(MSCs) after intraportal transplantation.METHODS:Mononuclear cells were isolated from bone marrow aspirates of pigs by density gradient centrifugation,cultured and expanded,after which,they were incubated with super paramagnetic iron oxide(SPIO).Prussian blue staining was performed to highlight intracellular iron.To establish swine models of acute liver injury,0.5 g/kg D-galactosamine was administrated to 10 pigs,six of which were injected via their portal veins with SPIO-labeled MSCs,while the remaining four were injected with unlabeled cells.Magnetic resonance imaging(MRI) was performed with a clinical 1.5T MR scanner immediately before transplantation and 6 h,3 d,7 d and 14 d after transplantation.Prussian blue staining was again performed with the tissue slices at the endpoint.RESULTS:Prussian blue staining of SPIO-labeled MSCs had a labeling efficiency of almost 100%.Signal intensity loss in the liver by SPIO labeling on the FFE(T2*WI) sequence persisted until 14 d after transplantation.Histological analysis by Prussian blue staining confirmed homing of labeled MSCs in the liver after 14 d;primarily distributed in hepatic sinusoids and liver parenchyma.CONCLUSION:MSCs were successfully labeled with SPIO in vitro.MRI can monitor magnetically labeled MSCs transplanted into the liver.

Umbilical Cord Blood-derived Mesenchymal Stem Cells Ameliorate Graft-Versus-Host Disease Following Allogeneic Hematopoietic Stem Cell Transplantation through Multiple Immunoregulations

Summary： Although mesenchymal stem cells （MSCs） are increasingly used to treat graft-versus-host disease （GVHD）, their immune regulatory mechanism in the process is elusive. The present study aimed to investigate the curative effect of third-party umbilical cord blood-derived human MSCs （UCB-hMSCs） on GVHD patients after allogeneic hematopoietic stem cell transplantation （allo-HSCT） and their immune regulatory mechanism. Twenty-four refractory GVHD patients after allo-HSCT were treated with UCB-hMSCs. Immune cells including T lymphocyte subsets, NK ceils, Treg cells and dendritic cells （DCs） and cytokines including interleukin-17 （IL-17） and tumor necrosis factor-alpha （TNF-α） were monitored before and after MSCs transfusion. The results showed that the symptoms of GVHD were alleviated significantly without increased relapse of primary disease and transplant-related complications after MSCs transfusion. The number of CD3^＋, CD3＋CD4^＋ and CD3＋CD8^＋ cells decreased significantly, and that of NK cells remained unchanged, whereas the number of CD4^＋ and CD8^＋ Tregs increased and reached a peak at 4 weeks; the number of mature DCs, and the levels of TNF-α and IL-17 decreased and reached a trough at 2 weeks. It was concluded that MSCs ameliorate GVHD and spare GVL effect via immunoregulations.

Cell transplantation to replace retinal ganglion cells faces challenges-the Switchboard Dilemma

The mammalian retina displays incomplete intrinsic regenerative capacities;therefore,retina degeneration is a major cause of irreversible blindness such as glaucoma,agerelated macular degeneration and diabetic retinopathy.These diseases lead to the loss of retinal cells and serious vision loss in the late stage.Stem cell transplantation is a great promising novel treatment for these incurable retinal degenerative diseases and represents an exciting area of regenerative neurotherapy.Several suitable stem cell sources for transplantation including human embryonic stem cells,induced pluripotent stem cells and adult stem cells have been identified as promising target populations.However,the retina is an elegant neuronal complex composed of various types of cells with different functions.The replacement of these different types of cells by transplantation should be addressed separately.So far,retinal pigment epithelium transplantation has achieved the most advanced stage of clinical trials,while transplantation of retinal neurons such as retinal ganglion cells and photoreceptors has been mostly studied in pre-clinical animal models.In this review,we opine on the key problems that need to be addressed before stem cells transplantation,especially for replacing injured retinal ganglion cells,may be used practically for treatment.A key problem we have called the Switchboard Dilemma is a major block to have functional retinal ganglion cell replacement.We use the public switchboard telephone network as an example to illustrate different difficulties for replacing damaged components in the retina that allow for visual signaling.Retinal ganglion cell transplantation is confronted by significant hurdles,because retinal ganglion cells receive signals from different interneurons,integrate and send signals to the correct targets of the visual system,which functions similar to the switchboard in a telephone network-therefore the Switchboard Dilemma.

Transplantation of low-power laser-irradiated olfactory ensheathing cells to promote repair of spinal cord injury in rats

BACKGROUND： Previous studies have demonstrated that low-power laser （LPL） irradiation can promote the regeneration of peripheral nerves and central nerves, as well as influence cellular proliferation. Therefore, it is thought to be a potential treatment for spinal cord injury. OBJECTIVE： Utilizing histological observations and behavioral evaluations, the aim of this study was to investigate the influence of transplanted olfactory ensheathing cells （OECs）, irradiated by LPL, on functional repair of rats following transversal spinal cord injury. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the animal experimental center in the First Affiliated Hospital of Xinjiang Medical University between January 2007 and February 2008. MATERIALS： A total of 52 Sprague Dawley rats were included in this experiment. Twelve rats were used to harvest OECs, some of which were irradiated by LPL on days 3, 5, and 7 in culture. The remaining 40 rats were used to establish T12 complete spinal cord transection injury. DMEM/F12 medium was purchased from Sigma, USA, Fluorogold was provided by Chemicon, USA, and the LY/JG650-D500-16 low-power laser was produced by Xi＇an Lingyue Electromechanical Science And Technology Co., Ltd., China. METHODS： The successful rat models were randomly divided into three groups： OEC transplantation, LPL-irradiated OEC transplantation, and control. These animals were microinjected with OEC suspension, LPL-irradiated OEC suspension, and DMEM/F12 medium （10μL） respectively 4 weeks after spinal cord was completely transected at the T12 level. MAIN OUTCOME MEASURES： Spinal cord injury was observed using hematoxylin-eosin staining Expression of nerve growth factor receptor p75 and glial fibrillary acidic protein were determined using immunohistochemical staining. Regeneration of spinal nerve fibers in rats was assayed by Fluorogold retrograde labeling method. Basso, Beattie and Bresnahan （BBB） scores were used to evaluate motor functions of rat lower limbs. RESULTS： Structural disturbances were observed following spinal cord injury in each group, and a large amount of scar tissue covered the broken ends, accompanied by porosis and inflammatory cell infiltration. Following OEC transplantation, the distal end connected to the proximal end. nerve growth factor receptor p75 and glial fibrillary acidic protein immunohistochemistry revealed positive OECs in the cephalad and caudal area of rats that received LPL-irradiated OEC transplantation. In the OECs group, only glial fibrillary acidic protein staining was observed. No staining was found in the control group. Neural fibers labeled with Fluorogold extended across the lesion area and into the cephalad and caudal area in the OECs and LPL-irradiated OECs groups, but were not present in the control group. BBB scores revealed statistically significant differences among the three groups （P 〈 0.05）： OECs irradiated by LPL group 〉 OECs group 〉 control group. CONCLUSION： Transplantation of OECs and LPL-irradiated OECs promoted functional repair in the injured spinal cord of rats, although LPL-irradiated OECs resulted in greater beneficial effects.

Optimal time for subarachnoid transplantation of neural progenitor cells in the treatment of contusive spinal cord injury

This study aimed to identify the optimal neural progenitor cell transplantation time for spinal cord injury in rats via the subarachnoid space. Cultured neural progenitor cells from 14-day embryonic rats, constitutively expressing enhanced green fluorescence protein, or media alone, were injected into the subarachnoid space of adult rats at 1 hour （acute stage）, 7 days （subacute stage） and 28 days （chronic stage） after contusive spinal cord injury. Results showed that grafted neural progenitor cells migrated and aggregated around the blood vessels of the injured region, and infiltrated the spinal cord parenchyma along the tissue spaces in the acute stage transplantation group. However, this was not observed in subacute and chronic stage transplantation groups. 04- and glial fibrillary acidic protein-positive cells, representing oligodendrocytes and astrocytes respectively, were detected in the core of the grafted cluster attached to the cauda equina pia surface in the chronic stage transplantation group 8 weeks after transplantation. Both acute and subacute stage transplantation groups were negative for 04 and glial fibrillary acidic protein cells. Basso, Beattie and Bresnahan scale score comparisons indicated that rat hind limb locomotor activity showed better recovery after acute stage transplantation than after subacute and chronic transplantation. Our experimental findings suggest that the subarachnoid route could be useful for transplantation of neural progenitor cells at the acute stage of spinal cord injury. Although grafted cells survived only for a short time and did not differentiate into astrocytes or neurons, they were able to reach the parenchyma of the injured spinal cord and improve neurological function in rats. Transplantation efficacy was enhanced at the acute stage in comparison with subacute and chronic stages.

Effect of endothelial progenitor cells derived from human umbilical cord blood on oxygen-induced retinopathy in mice by intravitreal transplantation

AIM： To investigate the effect of endothelial progenitor cells（EPCs） labeled by carboxy fluorescein diacetate succinimidyl ester（CFSE） on murine oxygen-induced retinopathy（OIR） by intravitreal transplantation.METHODS： After isolated from human umbilical cord blood mononuclear cells, EPCs were cultivated and then labeled with CFSE in vitro. C57BL/6J mice were placed to75% hyperoxia chamber from P7 to P12 to establish OIR model. At P12, OIR mice were intravitreally injected with1 μL suspension contained 2×105EPCs（EPCs group） or isometric phosphate buffered saline（PBS group）. The contralateral eye of each mice received no injection（OIR group）. Evans blue angiography and frozen section were examined to track the labeled cells in OIR group at P15 and P19. Using retina paraffin sections and adenosinediphos phatase staining at P12 and P19, the effect of EPCs on OIR mice was evaluated quantitatively and qualitatively. RESULTS： The retinas from EPCs group with less non-perfusion area and fewer peripheral tufts wereobserved at P19, comparing with that from PBS or OIR group. The retinopathy in EPCs group receded earlier with less non-ganglion cells and neovascular nuclei,together with relatively regular distribution. The counts of the neovascular nuclei at P19 were reduced by 44% or45%, compared with those of OIR group or PBS group respectively. Three days after EPCs injection, a large number of EPCs appeared in the vitreous cavity and adhered to the retinal surface. While at one week, the cells gathered between the internal plexiform layer and the inner limiting membrane, and some EPCs appeared in retinal vessels.CONCLUSION： EPCs transplantation can participate in the reparative procedure of the neovascularization in OIR.