Whole-eye transplantation: Current challenges and future perspectives

Whole-eye transplantation emerges as a frontier in ophthalmology,promising a transformative approach to irreversible blindness.Despite advancements,formidable challenges persist.Preservation of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell survival.Overcoming the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive,prompting the exploration of neurotrophic support and immunomodulatory interventions.Immunological tolerance,paramount for graft acceptance,confronts the distinc-tive immunogenicity of ocular tissues,driving research into targeted immunosup-pression strategies.Ethical and legal considerations underscore the necessity for stringent standards and ethical frameworks.Interdisciplinary collaboration and ongoing research endeavors are imperative to navigate these complexities.Biomaterials,stem cell therapies,and precision immunomodulation represent promising avenues in this pursuit.Ultimately,the aim of this review is to critically assess the current landscape of whole-eye transplantation,elucidating the challenges and advancements while delineating future directions for research and clinical practice.Through concerted efforts,whole-eye transplantation stands to revolu-tionize ophthalmic care,offering hope for restored vision and enhanced quality of life for those afflicted with blindness.

Overexpression of vascular endothelial growth factor enhances the neuroprotective effects of bone marrow mesenchymal stem cell transplantation in ischemic stroke

Although bone marrow mesenchymal stem cells(BMSCs)might have therapeutic potency in ischemic stroke,the benefits are limited.The current study investigated the effects of BMSCs engineered to overexpress vascular endothelial growth factor(VEGF)on behavioral defects in a rat model of transient cerebral ischemia,which was induced by middle cerebral artery occlusion.VEGF-BMSCs or control grafts were injected into the left striatum of the infarcted hemisphere 24 hours after stroke.We found that compared with the stroke-only group and the vehicle-and BMSCs-control groups,the VEGF-BMSCs treated animals displayed the largest benefits,as evidenced by attenuated behavioral defects and smaller infarct volume 7 days after stroke.Additionally,VEGF-BMSCs greatly inhibited destruction of the blood-brain barrier,increased the regeneration of blood vessels in the region of ischemic penumbra,and reducedneuronal degeneration surrounding the infarct core.Further mechanistic studies showed that among all transplant groups,VEGF-BMSCs transplantation induced the highest level of brain-derived neurotrophic factor.These results suggest that BMSCs transplantation with vascular endothelial growth factor has the potential to treat ischemic stroke with better results than are currently available.

Oxygen Penetration Through Full-Thickness Skin by Oxygen-Releasing Sutures for Skin Graft Transplantation

The transplantation of full-thickness skin grafts(FTSGs)is important for reconstructing skin barrier and promoting wound healing.Sufficient oxygen supply is closely related to the success of skin grafting.However,full-thickness oxygen delivery is limited by the poor oxygen permeability of skin.Oxygen-releasing sutures(O_(2)sutures)were developed to facilitate oxygen penetration through full-thickness skin.The O_(2)sutures delivered 100 times more oxygen than topical gaseous oxygen therapy at a 15 mm depth in the skin model.Under extreme hypoxia(<0.5%O_(2),v/v),O_(2)sutures could also promote endothelial cell proliferation.After the transplantation of FTSGs in mice,O_(2)sutures accelerated blood re-perfusion and increased the survival area of the skin graft.It is expected that O_(2)sutures will be adopted in clinical applications to increase the success rate of full-thickness skin transplantation.

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.

Phase 1 human trial of autologous bone marrow-hematopoietic stem cell transplantation in patients with decompensated cirrhosis

AIM: To evaluate safety and feasibility of autologous bone marrow-enriched CD34+ hematopoietic stem cell Tx through the hepatic artery in patients with decompensated cirrhosis.METHODS: Four patients with decompensated cirrhosis were included. Approximately 200 mL of the bone marrow of the patients was aspirated, and CD34+ stem cells were selected. Between 3 to 10 million CD34+ cells were isolated. The cells were slowly infused through the hepatic artery of the patients.RESULTS: Patient 1 showed marginal improvement in serum albumin and no significant changes in other test results. In patient 2 prothrombin time was decreased; however, her total bilirubin, serum creatinine, and Model of End-Stage Liver Disease (MELD) score worsened at the end of follow up. In patient 3 there was improvement in serum albumin, porthrombin time (PT), and MELD score. Patient 4 developed radiocontrast nephropathy after the procedure, and progressed to type 1 hepatorenal syndrome and died of liver failure a few days later. Because of the major side effects seen in the last patient, the trial was prematurely stopped.CONCLUSION: Infusion of CD34+ stem cells through the hepatic artery is not safe in decompensated cirrhosis. Radiocontrast nephropathy and hepatorenal syndrome could be major side effects. However, this study doesnot preclude infusion of CD34+ stem cells through other routes.

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.

Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells

AIM: To study the capacity of bone marrow mesenchymal stem cells (BM-MSCs) trans-differentiating into islet-like cells and to observe the effect of portal vein transplantation of islet-like cells in the treatment of streptozotocin-induced diabetic rat. METHODS: BM-MSCs were isolated from SD rats and induced to differentiate into islet-like cells under defined conditions. Differentiation was evaluated with electron microscopy, RT-PCR, immunofluorescence and flow cytometry. insulin release after glucose challenge was tested with ELiSA. Then allogeneic islet-like cells were transplanted into diabetic rats via portal vein. Blood glucose levels were monitored and islet hormones were detected in the liver and pancreas of the recipient by immunohistochemistry. RESULTS: BM-MSCs were spheroid adherent monolayers with high CD90, CD29 and very low CD45 expression. Typical islet-like cells clusters were formed after induction. Electron microscopy revealed that secretory granules were densely packed within the cytoplasm of the differentiated cells. The spheroid cells expressed islet related genes and hormones. The insulin-positive cells accounted for 19.8% and mean fluorescence intensity increased by 2.6 fold after induction. The cells secreted a small amount of insulin that was increased 1.5 fold after glucose challenge. After transplantation, islet-like cells could locate in the liver expressing islet hormones and lower the glucose levels of diabetic rats during d 6 to d 20.CONCLUSION: Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro . Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.

Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease

AIM： To evaluate the safety and feasibility of bone marrow cell （BMC） transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS： Ten patients （eight males） with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS： The median age of the patients was 52 years （range 24-70 years）. All patients were discharged 48 h after BMC infusion. Two patients complained ofmild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 （2.19 ± 0.9） and 4 mo （2.10 ± 1.0） after cell transplantation that baseline levels （238 ± 1.2）. Albumin levels 4 mo after BMC infusion （3.73 ± 0.5） were higher than baseline levels （3.47 ± 0.5）. International normalized ratio （INR） decreased from 1.48 （SD = 0.23） to 1.43 （SD = 0.23） one month after cell transplantation. CONCLUSION： BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease.

Glial cell-derived neurotrophic factor mRNA expression in a rat model of spinal cord injury following bone marrow stromal cell transplantation

BACKGROUND： Several animal experiments utilizing bone marrow stromal cell （BMSC） transplantation for the treatment of spinal cord injury have proposed a hypothesis that BMSC transplantation effects are associated with increased glial cell-derived neurotrophic factor （GDNF） expression. OBJECTIVE： To confirm the effects of BMSC transplantation on GDNF mRNA expression in rats with spinal cord injury by reverse transcription-polymerase chain reaction （RT-PCR）. DESIGN, TIME AND SETTING： The present molecular, cell biology experiment was performed at the Key Laboratory of Children＇s Congenital Malformation, Ministry of Health of China ＆ Department of Developmental Biology, Basic Medical College, China Medical University between March 2006 and May 2007. MATERIALS： Sixty healthy Wistar rats aged 2-4-months and of either gender were included in this study. Spinal cord injury was induced in all rats by hemisection of T9 on the left side. RT-PCR kits were purchased from TaKaRa Company, China. Type 9600 RCR amplifier was provided by Perkin Elmer Company, USA. METHODS： Three rats were selected for BMSC culture and subsequent transplantation （after three passages）. Of the remaining 57 rats, nine were selected for sham-operation （sham-operated group）, where only the T9 spinal cord was exposed without hemisection. A total of 48 rats were randomly and evenly divided into BMSC transplantation and model groups. In the BMSC transplantation group, following spinal cord injury induction, each rat was administered a BMSC suspension tbrougb two injection sites selected on the gray and white matter boundary caudally and cephalically, seperately and near to injury site in the spinal cord. The model group received an equal volume of PBS through the identical injection sites. MAIN OUTCOME MEASURES： At 24 and 72 hours, as well as at 7 days, following spinal cord injury, the spinal cord at the T9 segment was removed. Eight rats were allocated to each time point in the BMSC transplantation and model groups, with three rats allocated to the sham-operated group. GDNF mRNA expression was semiquantitatively analyzed by RT-PCR. RESULTS： The sham-operated group exhibited extremely low GDNF mRNA expression. GDNF mRNA expression significantly increased at 24 hours after spinal cord injury, reached a peak level at 72 hours, and slowly decreased thereafter. However, it remained higher than normal levels at 7 days （P 〈 0.05）. At all time points following spinal cord injury, GDNF mRNA expression was significantly greater in the BMSC transplantation group than in the model group （P 〈 0.05）. CONCLUSION： Transplantation of BMSCs into the injured spinal cord up-regulated GDNF mRNA expression, thereby promoting repair of the injured spinal cord.

Transplantation of bone marrow-derived endothelial progenitor cells and hepatocyte stem cells from liver fibrosis rats ameliorates liver fibrosis

AIM To explore the effectiveness for treating liver fibrosisby combined transplantation of bone marrow-derived endothelial progenitor cells(BM-EPCs) and bone marrow-derived hepatocyte stem cells(BDHSCs) from the liver fibrosis environment.METHODS The liver fibrosis rat models were induced with carbon tetrachloride injections for 6 wk. BM-EPCs from rats with liver fibrosis were obtained by different rates of adherence and culture induction. BDHSCs from rats with liver fibrosis were isolated by magnetic bead cell sorting. Tracing analysis was conducted by labeling EPCs with PKH26 in vitro to show EPC location in the liver. Finally, BM-EPCs and/or BDHSCs transplantation into rats with liver fibrosis were performed to evaluate the effectiveness of BM-EPCs and/or BDHSCs on liver fibrosis.RESULTS Normal functional BM-EPCs from liver fibrosis rats were successfully obtained. The co-expression level of CD133 and VEGFR2 was 63.9% ± 2.15%. Transplanted BM-EPCs were located primarily in/near hepatic sinusoids. The combined transplantation of BM-EPCs and BDHSCs promoted hepatic neovascularization, liver regeneration and liver function, and decreased collagen formation and liver fibrosis degree. The VEGF levels were increased in the BM-EPCs(707.10 ± 54.32) and BM-EPCs/BDHSCs group(615.42 ± 42.96), compared with those in the model group and BDHSCs group(P < 0.05). Combination of BM-EPCs/BDHSCs transplantation induced maximal up-regulation of PCNA protein and HGF m RNA levels. The levels of alanine aminotransferase(AST), aspartate aminotransferase, total bilirubin(TBIL), prothrombin time(PT) and activated partial thromboplastin time in the BMEPCs/BDHSCs group were significantly improved, to be equivalent to normal levels(P > 0.05) compared with those in the BDHSC(AST, TBIL and PT, P < 0.05) and BM-EPCs(TBIL and PT, P < 0.05) groups. Transplantation of BM-EPCs/BDHSCs combination significantly reduced the degree of liver fibrosis(staging score of 1.75 ± 0.25 vs BDHSCs 2.88 ± 0.23 or BMEPCs 2.75 ± 0.16, P < 0.05).CONCLUSION The combined transplantation exhibited maximal therapeutic effect compared to that of transplantation of BM-EPCs or BDHSCs alone. Combined transplantation of autogenous BM-EPCs and BDHSCs may represent a promising strategy for the treatment of liver fibrosis, which would eventually prevent cirrhosis and liver cancer.

Electrophysiological functional recovery in a rat model of spinal cord hemisection injury following bone marrow-derived mesenchymal stem cell transplantation under hypothermia

Following successful establishment of a rat model of spinal cord hemisection injury by resecting right spinal cord tissues, bone marrow stem cells were transplanted into the spinal cord lesions via the caudal vein while maintaining rectal temperature at 34 ± 0.5°C for 6 hours （mild hypothermia）. Hematoxylin-eosin staining showed that astrocytes gathered around the injury site and formed scars at 4 weeks post-transplantation. Compared with rats transplanted with bone marrow stem cells under normal temperature, rats transplanted with bone marrow stem cells under hypothermia showed increased numbers of proliferating cells （bromodeoxyuridine-positive cells）, better recovery of somatosensory-evoked and motor-evoked potentials, greater Basso, Beattie, and Bresnahan locomotor rating scores, and an increased degree of angle in the incline plate test. These findings suggested that hypothermia combined with bone marrow mesenchymal stem cells transplantation effectively promoted electrical conduction and nerve functional repair in a rat model of spinal cord hemisection injury.

Effects of heme oxygenase-1-modified bone marrow mesenchymal stem cells on microcirculation and energy metabolism following liver transplantation

AIM To investigate the effects of heme oxygenase-1(HO-1)-modified bone marrow mesenchymal stem cells(BMMSCs)on the microcirculation and energy metabolism of hepatic sinusoids following reduced-size liver transplantation(RLT)in a rat model.METHODS BMMSCs were isolated and cultured in vitro using an adherent method,and then transduced with HO-1-bearing recombinant adenovirus to construct HO-1/BMMSCs.A rat acute rejection model following 50%RLT was established using a two-cuff technique.Recipients were divided into three groups based on the treatment received:normal saline(NS),BMMSCs and HO-1/BMMSCs.Liver function was examined at six time points.The levels of endothelin-1(ET-1),endothelial nitric-oxide synthase(e NOS),inducible nitric-oxide synthase(i NOS),nitric oxide(NO),and hyaluronic acid(HA)were detected using an enzyme-linked immunosorbent assay.The portal vein pressure(PVP)was detected by Power Lab ML880.The expressions of ET-1,i NOS,e NOS,and von Willebrand factor(v WF)protein in the transplanted liver were detected using immunohistochemistry and Western blotting.ATPase in the transplanted liver was detected by chemical colorimetry,and the ultrastructural changes were observed under a transmission electron microscope.RESULTS HO-1/BMMSCs could alleviate the pathological changes and rejection activity index of the transplanted liver,and improve the liver function of rats following 50%RLT,with statistically significant differences compared with those of the NS group and BMMSCs group(P<0.05).In term of the microcirculation of hepatic sinusoids:The PVP on POD7 decreased significantly in the HO-1/BMMSCs and BMMSCs groups compared with that of the NS group(P<0.01);HO-1/BMMSCs could inhibit the expressions of ET-1 and i NOS,increase the expressions of e NOS and inhibit amounts of NO production,and maintain the equilibrium of ET-1/NO(P<0.05);and HO-1/BMMSCs increased the expression of v WF in hepatic sinusoidal endothelial cells(SECs),and promoted the degradation of HA,compared with those of the NS group and BMMSCs group(P<0.05).In term of the energy metabolism of the transplanted liver,HO-1/BMMSCs repaired the damaged mitochondria,and improved the activity of mitochondrial aspartate aminotransferase(ASTm)and ATPase,compared with the other two groups(P<0.05).CONCLUSION HO-1/BMMSCs can improve the microcirculation of hepatic sinusoids significantly,and recover the energy metabolism of damaged hepatocytes in rats following RLT,thus protecting the transplanted liver.

Olfactory ensheathing cell transplantation improves sympathetic skin responses in chronic spinal cord injury

Forty-three patients with chronic spinal cord injury for over 6 months were transplanted with bryonic olfactory ensheathing cells, 2-4 × 106, into multiple sites in the injured area under the sur-gical microscope. The sympathetic skin response in patients was measured with an electromyo-graphy/evoked potential instrument 1 day before transplantation and 3-8 weeks after trans-tion. Spinal nerve function of patients was assessed using the American Spinal Injury Association impairment scale. The sympathetic skin response was elicited in 32 cases before olfactory en-sheathing celltransplantation, while it was observed in 34 cases after transplantation. tantly, sympathetic skin response latency decreased significantly and amplitude increased cantly after transplantation. Transplantation of olfactory ensheathing cells also improved American Spinal Injury Association scores for movement, pain and light touch. Our findings indicate that factory ensheathing celltransplantation improves motor, sensory and autonomic nerve functions in patients with chronic spinal cord injury.

Protective effect of bone marrow mesenchymal stem cells in intestinal barrier permeability after heterotopic intestinal transplantation

AIM: To explore the protective effect of bone marrow mesenchymal stem cells (BM MSCs) in the small intestinal mucosal barrier following heterotopic intestinal transplantation (HIT) in a rat model.

Chitosan-collagen porous scaffold and bone marrow mesenchymal stem cell transplantation for ischemic stroke

In this study, we successfully constructed a composite of bone marrow mesenchymal stem cells and a chitosan-collagen scaffold in vitro, transplanted either the composite or bone marrow mesenchymal stem cells alone into the ischemic area in animal models, and compared their effects. At 14 days after co-transplantation of bone marrow mesenchymal stem cells and the hi- tosan-collagen scaffold, neurological function recovered noticeably. Vascular endothelial growth factor expression and nestin-labeled neural precursor cells were detected in the iscbemic area, surrounding tissue, hippocampal dentate gyrus and subventricular zone. Simultaneously, a high level of expression of glial fibrillary acidic protein and a low level of expression of neuron-spe- cific enolase were visible in BrdU-labeled bone marrow mesenchymal stem cells. These findings suggest that transplantation of a composite of bone marrow mesenchymal stem cells and a chi- tosan-collagen scaffold has a neuroprotective effect following ischemic stroke.

Effects of Guiyuanfang and autologous transplantation of bone marrow stem cells on rats with liver fibrosis

AIM: To investigate the therapeutic effects of Guiyuanfang and bone marrow stem cells (BMSCs) on rats with liver fibrosis.METHODS: Liver fibrosis model was induced by carbon tetrachloride, ethanol, high lipid and assessed biochemically and histologically. Liver function and hydroxyproline contents of liver tissue were determined.Serum hyaluronic acid (HA) level and procollagen Ⅲ level were performed by radioimmunoassay. The VG staining was used to evaluate the collagen deposit in the liver.Immunohistochemical SABC methods were used to detect transplanted BMSCs and expression of urokinase plasminogen activator (uPA).RESULTS: Serum transaminase level and liver fibrosis in rats were markedly reduced by Guiyuanfang and BMSCs. HA level and procollagen Ⅲ level were also reduced obviously,compared to model rats (HA: 47.18±10.97 ng/mL,48.96±14.79 ng/mL; PCⅢ: 22.48±5.46 ng/mL, 26.90±3.35ng/mL; P＜0.05).Hydroxyproline contents of liver tissue in both BMSCs group and Guiyuanfang group were far lower than that of model group (1 227.2±43.1 μg/g liver tissue, 1390.8±156.3 μg/g liver tissue; P＜0.01). After treatment fibrosis scores were also reduced. Both Guiyuanfang and BMSCs could increase the expression of uPA. The transplanted BMSCs could engraft, survive, and proliferate in the liver.CONCLUSION: Guiyuanfang protects against liver fibrosis.Transplanted BMSCs may engraft, survive, and proliferate in the fibrosis livers indefinitely. Guiyuanfang may synergize with BMSCs to improve recovery from liver fibrosis.

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.

visual bone marrow mesenchymal stem cell transplantation in the repair of spinal cord injury

An important factor in improving functional recovery from spinal cord injury using stem cells is maximizing the number of transplanted cells at the lesion site. Here, we established a contusion model of spinal cord injury by dropping a weight onto the spinal cord at T7_8. Superparamagnet- ic iron oxide-labeled bone marrow mesenchymal stem cells were transplanted into the injured spinal cord via the subarachnoid space. An outer magnetic field was used to successfully guide the labeled cells to the lesion site. Prussian blue staining showed that more bone marrow mesen- chymal stem cells reached the lesion site in these rats than in those without magnetic guidance or snperparamagnetic iron oxide labeling, and immunofluorescence revealed a greater number of complete axons at the lesion site. Moreover, the Basso, Beattie and Bresnahan （BBB） locomotor rating scale scores were the highest in rats with superparamagnetic labeling and magnetic guid- ance. Our data confirm that superparamagnetic iron oxide nanoparticles effectively label bone marrow mesenchymal stem cells and impart sufficient magnetism to respond to the external magnetic field guides. More importantly, superparamagnetic iron oxide-labeled bone marrow mesenchymal stem cells can be dynamically and non-invasively tracked in vivo using magnetic resonance imaging. Superparamagnetic iron oxide labeling of bone marrow mesenchymal stem cells coupled with magnetic guidance offers a promising avenue for the clinical treatment of spinal cord injury.

The future of bone marrow stromal cell transplantation for the treatment of spinal cord injury

Bone marrow stromal cell （BMSC） transplantation therapy is a promising approach for treating spinal cord injury （SCI）, based on a number of experimental and clinical reports （Wright et al., 2011）. BMSCs are a source of neuroregenerative somatic stem cells that are without the potential for tumorigenicity. Although clinical studies of autologous BMSC transplantation have been reported in Asia （fiang et al., 2013; Yoon et al., 2007）, in Japan, it is currently an uncommon procedure and highly controversial as well. This perspective paper provides an overview of the clinical effectiveness of BMSC trans- 191antation and a proposal to enhance its use as a viable therapy.

Tolerance and chimerism and allogeneic bone marrow/stem cell transplantation in liver transplantation

The liver has particular tolerogenic properties that allow its spontaneous acceptance in some animal species.Liver structure is considered to favor a tolerogenic environment.The peripheral tolerance mechanisms also play a role in spontaneous tolerance to liver graft.In a clinical setting,the main challenge nowadays facing liver transplantation is minimization of immunosuppression with the goal of donor-specific tolerance.Mechanisms involved in tolerance to transplanted organs are complex and partly unknown.A significant mechanism in tolerance induction is chimerism.Chimerism can be induced through transplantation of allogeneic donor bone marrow/stem cells under appropriate host conditioning.This review focuses on the tolerance mechanisms in liver transplantation and highlights the role of chimerism and allogeneic bone marrow/stem cell transplantation in tolerance development.