Cellular Transplantation Research Articles

CD28 gene polymorphisms and acute cellular rejection after liver transplantation

The co-stimulatory molecule CD28 plays an important role in T-cell-mediated immune response like acute cellular liver transplant rejection. The aim of the retrospective case- control study was to examine whether the single nucleotide polymorphisms (SNPs) rs3116487, rs3116494, and rs3116496 of the CD28 gene are associated with acute cellular liver transplant rejection. The mentioned SNPs were genotyped in 147 liver transplant recipients without acute cellular rejection and 144 liver transplant recipients with acute cellular rejection by real-time endpoint genotyping. The genotype and allele frequencies of the SNPs did not show any significant differences between both groups. Haplotype analyzes of the SNPs also showed no association. Our data suggest that the analyzed SNPs are not major contributors to the susceptibility of acute cellular liver transplant rejection.

S3551 Factors Related to Patient Outcomes Following Intestinal Transplant Surgery for Gunshot-Related Short Bowel Syndrome

INTRODUCTION: We discuss factors that may have contributed to variations in patient outcome after intestinal transplant surgery secondary to short bowel syndrome (SBS). Trends in this research are relevant for gastroenterologists considering intestinal transplant surgery for applicable patients. CASE DESCRIPTION/METHODS: A retrospective chart review was conducted for two intestinal transplant patients at a large urban medical center. Both patients underwent intestinal transplants secondary to SBS after small bowel resections for gunshot related injury (GSW). A 22-year old male underwent a small bowel and colon resection after injury from GSW, leading to the development of SBS. Eleven months later, he underwent an intestinal transplant surgery with a terminal ileostomy created. No co-morbidities were noted before transplant surgery; after transplant surgery, the patient developed acute kidney injury (AKI) and anemia. He was treated with Cidofovir and thymoglobulin for acute cellular and humoral transplant rejection via adenovirus enteritis at five years and again at eight years post-transplant. Complications secondary to acute transplant rejection led to enterectomy nine years post-transplant. A 37-year old male underwent a small bowel and right hemicolectomy after injury from GSW, leading to the development of SBS. Eight years later, he underwent an intestinal transplant surgery from a high-risk donor with a proximal jejunojejunostomy, distal ileo-colostomy, and ileostomy created. Surgical complications included congestion of graft and bowel edema. Co-morbidities before transplant surgery included history of DVT, cholecystectomy, and smoking history; after transplant surgery, the patient developed AKI, anemia, and inferior vena cava/superior mesenteric vein stenosis. The patient was treated with Cidofovir, plasmapheresis, and intravenous immunoglobin (IVIG) for acute cellular and humoral transplant rejection via adenovirus enteritis a month post-transplant. The patient passed away from complications secondary to acute transplant rejection eleven months post-transplant. DISCUSSION: Variations in patient outcome post-intestinal transplant are due to multi-factorial causes such as pre-transplant comorbidities, alterations in transplant surgical procedure, and severity of surgical complications. Further research is needed to examine the contribution of immunosuppression regimens, viral, social, and age-related factors on outcomes in intestinal transplantation.

Generation of Human Induced Pluripotent Stem Cells and Differentiation into Cardiomyocytes.

Failure to regenerate myocardium after injury is a major cause of mortality and morbidity in humans. Direct differentiation of human induced pluripotent stem cells (iPSCs) into cardiomyocytes provides an invaluable resource to pursue cardiac regeneration based on cellular transplantation. Beyond the potential for clinical therapies, iPSC technology also enables the generation of cardiomyocytes to recapitulate patient-specific phenotypes, thus presenting a powerful in vitro cell-based model to understand disease pathology and guide precision medicine. Here, we describe protocols for reprogramming of human dermal fibroblasts and blood cells into iPSCs using the non-integrative Sendai virus system and for the monolayer differentiation of iPSCs to cardiomyocytes using chemically defined media.

QUILTY LESION FOXP3+ AND TGF-BETA+ REGULATORY T-CELLS ARE ASSOCIATED WITH ACCEPTANCE OF HEART ALLOGRAFTS

To evaluate the cellular composition of Quilty lesions in heart transplant biopsies and their association with acceptance or rejection of cardiac allografts. In this study we included a cohort of cardiac transplant biopsies with Quilty lesions for which a final diagnosis had already been rendered for treatment purposes. Serial sections from 42 specimens were stained immunohistochemically for CD4, CD8, FoxP3 (as surrogate marker of innate regulatory T cells) and TGF-beta-1 (as surrogate marker of adaptive regulatory immune cells). The relative abundance of cells positive for each of these four markers was evaluated both in the Quilty lesion itself and in the uninvolved, surrounding myocardium using semi-quantitative methods. Correlations were then made, using chi-square and Pearson analysis, between these measures and allograft acceptance. FoxP3+ (OR 1.33, p<0.05) and TGF-beta+ cells (OR 1.4) in the quilty lesions are associated with higher allograft acceptance. Of note, no FoxP3+ cells were seen in myocardium. However, the presence of CD8+ cells in the myocardium is associated with greater degrees of both acute cellular (p<0.02) and antibody-mediated transplant rejection (p<0.04). High numbers of CD4+ cells in the myocardium are also associated with a greater degree of acute cellular rejection (p<0.04). However, the presence of either CD4+ or CD8+ T-cells in Quilty lesions are not associated with rejection. Interestingly, greater numbers of TGF-beta-positive cells in the myocardium are associated with a greater degree of antibody-mediated rejection. Quilty lesions previously have been associated with mild to moderate acute cellular rejection, but their precise function remains unclear: it has yet to be determined whether they might participate in immune-mediated tissue destruction or may represent an immune-mediated tissue salvage mechanism. In this study, both FoxP3+ innate and TGF-beta+ adaptive regulatory cells are associated with increased allograft acceptance in biopsies when localize? in quilty lesions. Myocardial effector CD4+ and CD8+ T-cells are associated with increased rejection. However, their presence in quilty lesions has no effect in rejection or acceptance or the transplant. Therefore, quilty lesions may rather represent intragraft tertiary lymphoid tissue to prevent allograft rejection, and assist in acceptance of the organ transplant. Drs. George and Anne Race Distinguished Professor of Pathology Endowment Fund (Dr. Jose Torrealba).

Characterization of Gelatin/Gellan Gum/Glycol Chitosan Ternary Hydrogel for Retinal Pigment Epithelial Tissue Reconstruction Materials.

The cellular transplantation approach to treat damaged or diseased retina is limited because of poor survival, distribution, and integration of cells after implantation to the sub-retinal space. To overcome this, it is important to develop a cell delivery system. In this study, a ternary hydrogel of gelatin (Ge)/gellan gum (GG)/glycol chitosan (CS) is suggested as a cell carrier for retinal tissue engineering (TE). Physicochemical properties such as porosity, swelling, sol fraction, and weight loss were measured. The mechanical study was performed with compressive strength and viscosity to confirm applicability in retinal TE. An in vitro experiment was carried out by encapsulating ARPE-19 in the designed hydrogel to measure viability and expression of retinal pigment epithelium-specific proteins and genes. The results showed that the ternary hydrogel system improves the mechanical properties and stability of the composite. Cell growth, survival, adhesion, and migration were enhanced as the CS was incorporated into the matrix. In particular, real-time polymerase chain reaction analysis showed a markedly improved specific gene expression rate in the Ge/GG/CS. Therefore, it is expected that the ternary system suggested in this study can be used as a promising material for retinal TE.

Combinatorial Immunotherapies for Metastatic Colorectal Cancer.

Colorectal cancer (CRC) is one of the most frequent and deadly forms of cancer. About half of patients are affected by metastasis, with the cancer spreading to e.g., liver, lungs or the peritoneum. The majority of these patients cannot be cured despite steady advances in treatment options. Immunotherapies are currently not widely applicable for this disease, yet show potential in preclinical models and clinical translation. The tumour microenvironment (TME) has emerged as a key factor in CRC metastasis, including by means of immune evasion—forming a major barrier to effective immuno-oncology. Several approaches are in development that aim to overcome the immunosuppressive environment and boost anti-tumour immunity. Among them are vaccination strategies, cellular transplantation therapies, and targeted treatments. Given the complexity of the system, we argue for rational design of combinatorial therapies and consider the implications of precision medicine in this context.

Stem cell therapies as a therapeutic option to counter chemo brain: a negative effect of cancer treatment.

Chemo brain, a constellation of cognitive deficiencies followed by chemotherapy drugs, used to treat different types of cancers and adversely impacts the quality of life of a cancer survivor. The underlying mechanism of chemo brain remains vague, thus delaying the advancement of efficient treatments. Unfortunately, there is no US FDA approved medicine for chemo brain and often medicines considered for chemo brain are already the ones approved for other diseases. Nevertheless, researches exploring stem cell transplantation in different neurodegenerative diseases demonstrate that cellular transplantation could reverse chemotherapy-induced chemo brain. This review talks about the mechanism behind the cognitive impairments instigated by different chemotherapy drugs used in cancer treatment, and how stem cell therapy could be advantageous to overcome this disease.

Modeling and optimizing a polycaprolactone/gelatin/polydimethylsiloxane nanofiber scaffold for tissue engineering: using response surface methodology

Patients suffering from diseased or injured parts of their body could be treated with transplanted tissue, organ, or parts of them; however, there is a severe shortage of allogeneic engrafts that is worsening annually. In the field of tissue engineering and medical rehabilitation, scientists apply the principles of cellular transplantation, material science, and environmental engineering to build biological substitutes that rehabilitate and maintain part of normal function in injured and damaged tissues. In this study, the production process of a biocompatible scaffold made from polycaprolactone/gelatin/polydimethylsiloxane (PCL/GEL/PDMS) and its optimization using response surface methodology (RSM) method has been reported. The PCL/GEL/PDMS blend ratio, their interactions and their solubility were investigated on the mechanical properties, biodegradability, and biocompatibility of nanofibers. These variables have a quadratic relationship with the PCL/GEL/PDMS blend ratio. With the experimental design, PCL/GEL/PDMS optimization scaffold was fabricated as a scaffold for tissue engineering. These results indicate that the PCL/GEL/PDMS scaffold is a novel biocompatible scaffold, suitable for tissue engineering.

Stem Cell Clinical Trials in Spinal Cord Injury: A Brief Review of Studies in the United States

Background: Although many therapeutic approaches have been attempted to treat spinal cord injury, cellular transplantation offers the greatest promise in reconstituting the architecture of the damaged cord. Methods: A literature review was conducted to search for clinical trials investigating stem cells as treatment for spinal cord injury in the United States. Results: Overall, eight studies met inclusion criteria. Of the included studies, four were identified as being terminated, suspended, or not yet recruiting. Two studies were identified as currently recruiting, including one phase one trial evaluating stereotactic injections of human spinal cord-derived neural stem cells in patients with chronic spinal cord injuries, and one trial of transplantation of autologous bone marrow derived stem cells via paraspinal injections, intravenous injections, and intranasal placement. One study was identified as an active study, a phase one trial of intrathecal injection of 100 million autologous, ex-vivo expanded, adipose-derived mesenchymal stem cells. One trial that was listed as completed is a phase 1/2a, dose escalation study, investigating stereotactic injection of human embryonic stem cell derived oligodendrocyte progenitor cells. Conclusions: Although few significant publications have emerged to this point, current trial results are promising.

Integration of nano- and biotechnology for beta-cell and islet transplantation in type-1 diabetes treatment.

Regenerative medicine using human or porcine β‐cells or islets has an excellent potential to become a clinically relevant method for the treatment of type‐1 diabetes. High‐resolution imaging of the function and faith of transplanted porcine pancreatic islets and human stem cell–derived beta cells in large animals and patients for testing advanced therapy medicinal products (ATMPs) is a currently unmet need for pre‐clinical/clinical trials. The iNanoBIT EU H2020 project is developing novel highly sensitive nanotechnology‐based imaging approaches allowing for monitoring of survival, engraftment, proliferation, function and whole‐body distribution of the cellular transplants in a porcine diabetes model with excellent translational potential to humans. We develop and validate the application of single‐photon emission computed tomography (SPECT) and optoacoustic imaging technologies in a transgenic insulin‐deficient pig model to observe transplanted porcine xeno‐islets and in vitro differentiated human beta cells. We are progressing in generating new transgenic reporter pigs and human‐induced pluripotent cell (iPSC) lines for optoacoustic imaging and testing them in transplantable bioartificial islet devices. Novel multifunctional nanoparticles have been generated and are being tested for nuclear imaging of islets and beta cells using a new, high‐resolution SPECT imaging device. Overall, the combined multidisciplinary expertise of the project partners allows progress towards creating much needed technological toolboxes for the xenotransplantation and ATMP field, and thus reinforces the European healthcare supply chain for regenerative medicinal products.

Encapsulation of Human Natural and Induced Regulatory T‐Cells in IL‐2 and CCL1 Supplemented Alginate‐GelMA Hydrogel for 3D Bioprinting

AbstractRegulatory T‐cells (Tregs) are important modulators of the immune system through their intrinsic suppressive functions. Systemic adoptive transfer of ex vivo expanded Tregs has been extensively investigated for allogeneic transplantation. Due to the time‐consuming and costly expansion protocols of Tregs, more targeted approaches could be beneficial. The encapsulation of human natural and induced Tregs for localized immunosuppression is described for the first time. Tregs encapsulated in alginate‐gelatin methacryloyl hydrogel remain viable, phenotypically stable, functional, and confined in the structure. Supplementation of the hydrogel with the Treg‐specific bioactive factors interleukin‐2 and chemokine ligand 1 improves Treg viability, suppressive phenotype, and function, and attracts to the structure CCR8+ T‐cells enriched with anti‐inflammatory subpopulations, including Tregs, from human peripheral blood. Furthermore, these findings are applicable to 3D bioprinting. Co‐axial printing of murine pancreatic islets with human natural and induced Tregs protects the islets from xenoresponse upon co‐culture with human peripheral blood mononuclear cells. This establishes the co‐encapsulation of Tregs by co‐axial 3D bioprinting as a valid option for providing local immune protection to allogeneic cellular transplants such as pancreatic islets.

Mutually beneficial effects of intensive exercise and GABAergic neural progenitor cell transplants in reducing neuropathic pain and spinal pathology in rats with spinal cord injury

Spinal cord injury (SCI) produces both locomotor deficits and sensory dysfunction that greatly reduce the overall quality of life. Mechanisms underlying chronic pain include increased neuro-inflammation and changes in spinal processing of sensory signals, with reduced inhibitory GABAergic signaling a likely key player. Our previous research demonstrated that spinal transplantation of GABAergic neural progenitor cells (NPCs) reduced neuropathic pain while intensive locomotor training (ILT) could reduce development of pain and partially reverse already established pain behaviors. Therefore, we evaluate the potential mutually beneficial anti-hypersensitivity effects of NPC transplants cells in combination with early or delayed ILT. NPC transplants were done at 4 weeks post-SCI. ILT, using a progressive ramping treadmill protocol, was initiated either 5 days post-SCI (early: pain prevention group) or at 5 weeks post-SCI (delayed: to reverse established pain) in male Sprague Dawley rats. Results showed that either ILT alone or NPCs alone could partially attenuate SCI neuropathic pain behaviors in both prevention and reversal paradigms. However, the combination of ILT with NPC transplants significantly enhanced neuropathic pain reduction on most of the outcome measures including tests for allodynia, hyperalgesia, and ongoing pain. Immunocytochemical and neurochemical analyses showed decreased pro-inflammatory markers and spinal pathology with individual treatments; these measures were further improved by the combination of either early or delayed ILT and GABAergic cellular transplantation. Lumbar dorsal horn GABAergic neuronal and process density were nearly restored to normal levels by the combination treatment. Together, these interventions may provide a less hostile and more supportive environment for promoting functional restoration in the spinal dorsal horn and attenuation of neuropathic pain following SCI. These findings suggest mutually beneficial effects of ILT and NPC transplants for reducing SCI neuropathic pain.

In Vitro Evaluation of a Novel Synthetic Bilirubin Analog as an Antioxidant and Cytoprotective Agent for Pancreatic Islet Transplantation

Bilirubin is a natural cytoprotective agent and physiologic doses have proven to be beneficial in various models of organ and cellular transplantation. Recently, we showed that bilirubin has protective effects in models of pancreatic islet transplantation, preventing cell death associated with islet stress and suppressing the release of damage-associated molecular patterns. Despite these promising therapeutic attributes, the natural bilirubin used in these research studies is animal-derived (porcine), making it unsuitable for clinical application. In the current study, we synthesized two bilirubin analogs that can be produced without the use of animal-derived products. Antioxidant activity for the analogs was measured using the ferric-reducing-ability-of-plasma (FRAP) and 2,2V-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) assays. Dose-dependent cytotoxicity and cytoprotective effects were then demonstrated in isolated rat islets. Compound 1 showed similar antioxidant activity to natural bilirubin. Dose-dependent cytotoxicity was seen following treatment with Compound 1 and natural bilirubin at doses >40 μM, resulting in significantly increased cell death when compared to control islets (P < 0.05) or islets treated with doses ≤20 μM (P < 0.05). Following hypoxic challenge, islet cell death was reduced in islets treated with Compound 1 at 10 μM (17.27% ± 0.26%) compared to natural bilirubin at 10 μM (51.36% ± 0.71%; P < 0.0001) or 20 μM (59.02% ± 0.83%; P < 0.0001) and control islets (36.51% ± 0.44%; P < 0.0001). Compound 1 was found to have promising antioxidant and cytoprotective effects, limiting islet cell death in a model of islet transplantation hypoxic stress. Compound 1 may serve as a synthetic drug lead for clinical islet transplantation and further evaluation of this molecule and its analogs is warranted.

Hematopoietic Stem Cell Transplantation, Where Have We Come and Where Do We Go.

Hematopoietic cellular transplantation (HCT) has impacted medicine beyond simply treating certain diseases. Allogeneic HCT was the first documented successful immunological cellular therapy. Its usage continues to increase. The immunological disparity between donor and recipient has been associated with better antitumor efficacy as well as immunological toxicities. Through active clinical trials and research, considerable improvements in HCT therapy have been made over the past 50 years. The HCT international outcomes registry has considerably contributed to these improvements by identifying factors that could never be studied by a single center. With the use of unrelated donors, international collaboration increased as donor cell access through registries was not inhibited by international boundaries. HCT as a field pioneered the development of organizations for self-regulation that were assessing the entire program as an integrated whole rather than simply assessing facilities and providers separately.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene polymorphisms in liver transplant donors and impact on acute cellular liver transplant rejection.

The PTPN22 gene encodes the lymphoid protein tyrosine phosphatase involved in regulation the immune response. The single nucleotide polymorphisms (SNPs) rs1217388, rs1310182, rs2476601, and rs2488457 are located within the PTPN22 gene. We investigated whether these SNPs in liver transplant donors are associated with acute cellular rejection in the recipients. The SNPs were analyzed in donors (n = 104) of recipients who did not develop an acute cellular rejection and in donors (n = 53) of corresponding recipients developing an acute cellular rejection. No significant differences in genotype and allele frequencies of these SNPs were detected in either of the group. Our data suggest that these SNPs in liver transplant donors have no impact on the susceptibility of acute cellular liver transplant rejection.

Cellular therapies

Cellular therapies Abstract. Transfusion medicine and allogeneic stem cell transplantation are well known and established cellular therapies in hematology. Since decades many efforts have been made, in order to re-program the patient's own immune system in order to clear malignancies. A breakthrough was achieved with the manufacturing and optimizing of so-called chimeric antigen receptor (CAR) T-cells, genetically engineered cells, specifically directed against tumor antigens. In this review we discuss the structure of CAR T-cells, their manufacturing and the different steps of a CAR T-cell treatment according to the current licensing. Furthermore, we give an outlook on future prospects of cellular therapies including the major issues in the field.

Molecular mechanism of microRNA in regulating cochlear hair cell development

Deafness has become one of the most frequent health problems worldwide, and affects almost every age group. Hair cell damage or absence is the main cause of hearing loss, but there is no successful treatment to heal deafness. MicroRNA (miRNA), as a highly conserved endogenous non-coding small RNA, plays an important role in inner ear cochlea and hair cell development. In this review, we elaborate on the expression and function of miRNAs in cochlear hair cell development, and reveal its indispensable important role. We summarize the molecular mechanism of miRNA in regulating transcription factors involved in cochlear hair cell development, which may provide references and insights for hair cell regeneration in vivo and cellular transplantation therapy of deafness.

Promoting Dendrimer Self-Assembly Enhances Covalent Layer-by-Layer Encapsulation of Pancreatic Islets.

For type 1 diabetics, islet transplantation can induce beneficial outcomes, including insulin independence and improved glycemic control. The long-term function of the grafted tissue, however, is challenged by host inflammatory and immune responses. Cell encapsulation can decrease detrimental host responses to the foreign implant, but standard microencapsulation imparts large transplant volumes and impaired metabolite and nutrient diffusion. To mitigate these effects, we developed an efficient covalent Layer-by-Layer (cLbL) approach for live-cell nanoencapsulation, based on oppositely charged hyperbranched polymers functionalized with complementary Staudinger ligation groups. Reliance on cationic polymers for cLbL, however, is problematic due to their poor biocompatibility. Herein, we incorporated the additional feature of supramolecular self-assembly of the dendritic polymers to enhance layer uniformity and decrease net polymer charge. Functionalization of poly (amino amide) (PAMAM) with triethoxysilane decreased polymer charge without compromising the uniformity and stability of resulting nanoscale islet coatings. Encapsulated pancreatic rat islets were viable and functional. The implantation of cLbL islets into diabetic mice resulted in stable normoglycemia, at equivalent dosage and efficiency as uncoated islets, with no observable alterations in cellular engraftment or foreign body responses. By balancing multi-functionality and self-assembly, nano-scale and stable covalent layer-by-layer polymeric coatings could be efficiently generated onto cellular organoids, presenting a highly adaptable platform for broad use in cellular transplantation.

Selective inhibition of cyclooxygenase-2 protects porcine aortic endothelial cells from human antibody-mediated complement-dependent cytotoxicity.

Cyclooxygenase-2 (COX-2) is an inducible enzyme with catalytic activity for biosynthesis of prostaglandins which are the key mediators of inflammation. COX-2 is also the therapeutic target for widely used non-steroidal anti-inflammatory drugs (NSAIDs). However, the involvement of COX-2 in xenotransplantation (eg, pig-to-non-human primate) remains poorly recognized. We investigatedthe mechanisms that regulate COX-2 expression and the effects of COX-2 on porcine aortic endothelial cell (PAEC) viability using in vitro pig-to-primate xenotransplantation modelandin vivopig-to-mouse cellular transplant model. Regulation of COX-2 expression was assessed by real-time quantitative polymerase chain reaction (qPCR) and Western blotting. The effects of inhibition or downregulation of COX-2 on PAEC viability were assessed by propidium iodide (PI)-Annexin V staining and Cell Counting Kit-8 assay. Human serum triggered robust COX-2 expression in PAECs in a dose- and time-dependent manner. Induction of COX-2 expression by human serum was partially through activation of both canonical and non-canonical nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κb) signaling and increasing intracellular calcium. Cytokines like tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), IL-17, were able to induce COX-2 expression. Selective inhibition of COX-2 by celecoxib dramatically decreased PAEC death in vitro and in vivo as defined by propidium iodide (PI)-Annexin V staining. Consistently, downregulation of COX-2 expression by NF-κb inhibitors or calcium chelator BAPTA decreased human serum-induced PAEC death as well. Silencing of COX-2 expression by small interfering RNA (siRNA) protected PAEC viability when transplanted under kidney capsule of C57BL/6 mice. Taken together, our data suggest that COX-2 is highly induced in PAECs by xenogenic serum and associated with human antibody-mediated complement-dependent cytotoxicity. COX-2 might be a potential therapeutic target to improve xenotransplantation.

Intravenous transplantation of olfactory bulb ensheathing cells for a spinal cord hemisection injury rat model

Cellular transplantation strategies utilizing intraspinal or intrathecal olfactory ensheathing cells (OECs) have been reported as beneficial for spinal cord injury (SCI). However, there are many disadvantages of these methods, including additional trauma to the spinal cord parenchyma and technical challenges. Therefore, we investigated the feasibility and potential benefits of intravenous transplantation of OECs in a rat hemisection SCI model. OECs derived from olfactory bulb tissue were labeled with quantum dots (QDs), and their biodistribution after intravenous transplantation was tracked using a fluorescence imaging system. Accumulation of the transplanted OECs was observed in the injured spinal cord within 10 min, peaked at seven days after cell transplantation, and decreased gradually thereafter. This time window corresponded to the blood–spinal cord barrier (BSCB) opening time, which was quantitated with the Evans blue leakage assay. Using immunohistochemistry, we examined neuronal growth (GAP-43), remyelination (MBP), and microglia (Iba-1) reactions at the lesion site. Motor function recovery was also measured using a classic open field test (Basso, Beattie and Bresnahan score). Compared with the group injected only with QDs, the rats that received OEC transplantation exhibited a prominent reduction in inflammatory responses, increased neurogenesis and remyelination, and significant improvement in motor function. We suggest that intravenous injection could also be an effective method for delivering OECs and improving functional outcomes after SCI. Moreover, the time course of BSCB disruption provides a clinically relevant therapeutic window for cell-based intervention.