Transplantation Of Human Amniotic Epithelial Cells Research Articles

Human amniotic epithelial cell transplantation is safe and well tolerated in patients with compensated cirrhosis: a first-in-human trial.

Placenta-derived human amniotic epithelial cells (hAEC) exhibit anti-inflammatory and anti-fibrotic effects in cirrhosis models. We conducted a first-in-human phase I clinical trial to assess the safety and tolerability of hAEC in adults with compensated cirrhosis. We examined increasing and repeated doses of hAEC in 9 patients in 3 cohorts. Cohort 1 patients received 0.5 × 106/kg hAEC in one IV infusion. Cohort 2 patients received 1 × 106/kg hAEC in one IV infusion. The patients in cohort 3 received 1 × 106/kg hAEC on days 0 and 28. Here, we report follow-up to post-infusion day 56 (D56), during which no serious adverse events occurred. Six patients experienced no study-related adverse events, while 3 patients reported mild (grade 1) headaches that were possibly infusion-related. A transient decrease in serum platelet count occurred in all patients, which returned to baseline screening values by day 5. FIB-4 values to assess fibrosis were significantly lower at D56. Although not statistically significant, serum AST levels and liver stiffness measurements at D56 were lower than those at baseline. The hepatic venous pressure gradient, a measure of portal hypertension, declined in 4 patients, did not change in 3 patients, and increased in 2 patients. In conclusion, intravenous infusion of allogeneic hAEC in patients with compensated cirrhosis at the doses used in this study was safe and well tolerated, with no difference observed between 1 and 2 doses. Decreased hepatic inflammation, liver stiffness, and portal hypertension support larger studies aimed at identifying patients who may benefit from this therapy. Clinical Trial registration: The trial was prospectively entered on the Australian Clinical Trials Registry (ANZCTR12616000437460).

Human amniotic epithelial cell transplantation improves scar remodeling in a rabbit model of acute vocal fold injury: a pilot study

ObjectiveTo gain insight into the molecular mechanisms underlying the early stages of vocal fold extracellular matrix (ECM) remodeling after a mid-membranous injury resulting from the use of human amniotic epithelial cells (hAEC), as a novel regenerative medicine cell-based therapy.MethodsVocal folds of six female, New Zealand White rabbits were bilaterally injured. Three rabbits had immediate bilateral direct injection of 1 × 106 hAEC in 100 µl of saline solution (hAEC) and three with 100 µl of saline solution (controls, CTR). Rabbits were euthanized 6 weeks after injury. Proteomic analyses (in-gel trypsin protein digestion, LC–MS/MS, protein identification using Proteome Discoverer and the Uniprot Oryctolagus cuniculus (Rabbit) proteome) and histological analyses were performed.ResultshAEC treatment significantly increased the expression of ECM proteins, elastin microfibril interface-located protein 1 (EMILIN-1) and myocilin that are primarily involved in elastogenesis of blood vessels and granulation tissue. A reactome pathway analysis showed increased activity of the anchoring fibril formation by collagen I and laminin, providing mechanical stability and activation of cell signaling pathways regulating cell function. hAEC increased the abundance of keratin 1 indicating accelerated induction of the differentiation programming of the basal epithelial cells and, thereby, improved barrier function. Lastly, upregulation of Rab GDP dissociation inhibitor indicates that hAEC activate the vesicle endocytic and exocytic pathways, supporting the exosome-mediated activation of cell–matrix and cell-to-cell interactions.ConclusionsThis pilot study suggests that injection of hAEC into an injured rabbit vocal fold favorably alters ECM composition creating a microenvironment that accelerates differentiation of regenerated epithelium and promotes stabilization of new blood vessels indicative of accelerated and improved repair.

A combination of lycopene and human amniotic epithelial cells can ameliorate cognitive deficits and suppress neuroinflammatory signaling by choroid plexus in Alzheimer's disease rat

Neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to be correlated with cognitive deficits in Alzheimer's disease (AD). Previously, some studies have demonstrated that lycopene (LYCO) or human amniotic epithelial cells (HAECs) could attenuate inflammation in AD. Specifically, the choroid plexus (CP), an epithelial layer that forms the blood-cerebrospinal fluid barrier, is able to modulate the cognitive function, through changes in the neuroinflammatory response and in brain immune surveillance. However, it is unclear if LYCO can interact with HAECs to improve neuroinflammation at the CP. Thus, this study chose the region of interest, considered the feasibility of using a combination of LYCO and HAECs, as a therapeutic agent for immunomodulatory effects at the CP in an acutely induced AD rat model. Results showed that oral administration of LYCO, HAECs transplantation, and their combination significantly improved cognitive deficits in water maze test, decreased the level of proinflammatory mediators (TNF-α and IL-1β), increased the level of anti-inflammatory mediators (IL-10 and TGF-β1) in the cerebro-spinal fluid, and hippocampal tissue. Interestingly, LYCO administration, HAECs transplantation and their combination reversed the Aβ1–42 induced up-regulation of Toll like receptor 4 and nuclear factor-κB p65 mRNA and protein expressions at the CP. This study provided the novel experimental evidence for the influence of co-treatment with LYCO and HAECs on immunomodulatory capabilities of CP. It could also warrant therapeutic window for the pathophysiology of AD and the associated underlying mechanisms at the CP.

Human amniotic epithelial cell transplantation promotes neurogenesis and ameliorates social deficits in BTBR mice

BackgroundAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and communication and stereotypical patterns of behaviors, interests, or activities. Even with the increased prevalence of ASD, there is no defined standard drug treatment for ASD patients. Currently, stem cells, including human amniotic epithelial cell (hAEC) transplantation, seem to be a promising treatment for ASD, but the effectiveness needs to be verified, and the mechanism has not been clarified.MethodsWe intraventricularly transplanted hAECs into a 2-month-old BTBR T+tf/J (BTBR) mouse model of ASD. Behavior tests were detected 1 month later; hippocampal neurogenesis, neuroprogenitor cell (NPC) pool, and microglia activation were analyzed with immunohistochemistry and immunofluorescence; the levels of pro-inflammatory cytokines, brain-derived neurotrophic factor (BDNF), and TrkB in the hippocampus were determined by real-time PCR or western blotting.ResultsAfter intraventricular injection of hAECs into adult males, social deficits in BTBR mice were significantly ameliorated. In addition, hAEC transplantation restored the decline of neurogenesis and NPCs in the hippocampus of BTBR mice by expanding the stem cell pool, and the decreased levels of BDNF and TrkB were also rescued in the hippocampus of the hAEC-injected BTBR mice. Meanwhile, the transplantation of hAECs did not induce microglial overactivation or excessive production of pro-inflammatory cytokines in the hippocampus of BTBR mice.ConclusionsBased on these results, we found that hAEC transplantation ameliorated social deficits and promoted hippocampal neurogenesis in BTBR mice. Our study indicates a promising therapeutic option that could be applied to ASD patients in the future.

Liver-Directed Human Amniotic Epithelial Cell Transplantation Improves Systemic Disease Phenotype in Hurler Syndrome Mouse Model.

Mucopolysaccharidosis type 1 (MPS1) is an inherited lysosomal storage disorder caused by a deficiency in the glycosaminoglycan (GAG)‐degrading enzyme α‐l‐iduronidase (IDUA). In affected patients, the systemic accumulation of GAGs results in skeletal dysplasia, neurological degeneration, multiple organ dysfunction, and early death. Current therapies, including enzyme replacement and bone marrow transplant, improve life expectancy but the benefits to skeletal and neurological phenotypes are limited. In this study, we tested the therapeutic efficacy of liver‐directed transplantation of a placental stem cell, which possesses multilineage differentiation potential, low immunogenicity, and high lysosomal enzyme activity. Unfractionated human amniotic epithelial cells (hAECs) were transplanted directly into the liver of immunodeficient Idua knockout mouse neonates. The hAECs engraftment was immunohistochemically confirmed with anti‐human mitochondria staining. Enzyme activity assays indicated that hAECs transplantation restored IDUA function in the liver and significantly decreased urinary GAG excretion. Histochemical and micro‐computed tomography analyses revealed reduced GAG deposition in the phalanges joints and composition/morphology improvement of cranial and facial bones. Neurological assessment in the hAEC treated mice showed significant improvement of sensorimotor coordination in the hAEC treated mice compared to untreated mice. Results confirm that partial liver cell replacement with placental stem cells can provide long‐term (>20 weeks) and systemic restoration of enzyme function, and lead to significant phenotypic improvement in the MPS1 mouse model. This preclinical data indicate that liver‐directed placental stem cell transplantation may improve skeletal and neurological phenotypes of MPS1 patients. Stem Cells Translational Medicine 2017;6:1583–1594

Mechanisms of human amniotic epithelial cell transplantation in treating stage III pressure ulcer in a rat model.

The aim of the present study was to determine the function of human amniotic epithelial cell transplantation (hAECT) in promoting the healing of rats with stage III pressure ulcer (PU) and to initially investigate its possible mechanisms. A total of 96 Sprague Dawley rats were allocated at random into the model, hAECT, conventional treatment or control groups (n=24 per group). In each group, 6 rats were observed to determine the wound-healing rate. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-α in the wound tissue and serum were detected using reverse transcription-quantitative polymerase chain reaction analysis and enzyme-linked immunosorbent assay. The transplantation of hAECs significantly increased the healing rate of the stage III PUs and was accompanied by the significant upregulation of VEGF mRNA and protein expression levels and the significant downregulation of TNF-α mRNA and protein expression. Immunofluorescence staining showed that, on day 7 of transplantation, hAECs remained alive inside the skin tissues. Therefore, hAECT through subcutaneous injection appears to significantly improve the wound-healing rate of stage III PUs in rats, and this effect may be associated with the upregulation of the proangiogenic factor VEGF and the downregulation of the inflammatory cytokine TNF-α.

Human amniotic epithelial cell transplantation for the repair of injured brachial plexus nerve: evaluation of nerve viscoelastic properties.

The transplantation of embryonic stem cells can effectively improve the creeping strength of nerves near an injury site in animals. Amniotic epithelial cells have similar biological properties as embryonic stem cells; therefore, we hypothesized that transplantation of amniotic epithelial cells can repair peripheral nerve injury and recover the creeping strength of the brachial plexus nerve. In the present study, a brachial plexus injury model was established in rabbits using the C6 root avulsion method. A suspension of human amniotic epithelial cells was repeatedly injected over an area 4.0 mm lateral to the cephal and caudal ends of the C6 brachial plexus injury site (1 × 106 cells/mL, 3 μL/injection, 25 injections) immediately after the injury. The results showed that the decrease in stress and increase in strain at 7,200 seconds in the injured rabbit C6 brachial plexus nerve were mitigated by the cell transplantation, restoring the viscoelastic stress relaxation and creep properties of the brachial plexus nerve. The forepaw functions were also significantly improved at 26 weeks after injury. These data indicate that transplantation of human amniotic epithelial cells can effectively restore the mechanical properties of the brachial plexus nerve after injury in rabbits and that viscoelasticity may be an important index for the evaluation of brachial plexus injury in animals.

Human Amniotic Epithelial Cells Transplantation can Differentiate to Granulosa Cells and Restore Folliculogenesis in a Mouse Model of Chemotherapy-Induced Premature Ovarian Failure

Human Amniotic Epithelial Cells Transplantation can Differentiate to Granulosa Cells and Restore Folliculogenesis in a Mouse Model of Chemotherapy-Induced Premature Ovarian Failure

Human Amniotic Epithelial Cell Transplantation Induces Markers of Alternative Macrophage Activation and Reduces Established Hepatic Fibrosis

Chronic hepatic inflammation from multiple etiologies leads to a fibrogenic response that can progress to cirrhosis and liver failure. Transplantation of human amniotic epithelial cells (hAEC) from term delivered placenta has been shown to decrease mild to moderate hepatic fibrosis in a murine model. To model advanced human liver disease and assess the efficacy of hAEC therapy, we transplanted hAEC in mice with advanced hepatic fibrosis. Immunocompetent C57BL/6 mice were administered carbon tetrachloride (CCl4) twice weekly resulting in bridging fibrosis by 12 weeks. hAEC (2×106) were infused via the tail vein at week 8 or weeks 8 and 10 (single and double dose, respectively). Human cells were detected in mouse liver four weeks after transplantation showing hAEC engraftment. CCl4 treated mice receiving single or double hAEC doses showed a significant but similar decrease in liver fibrosis area associated with decreased activation of collagen-producing hepatic stellate cells and decreased hepatic protein levels of the pro-fibrogenic cytokine, transforming growth factor-beta1. CCl4 administration caused hepatic T cell infiltration that decreased significantly following hAEC transplantation. Hepatic macrophages play a crucial role in both fibrogenesis and fibrosis resolution. Mice exposed to CCl4 demonstrated increased numbers of hepatic macrophages compared to normal mice; the number of macrophages decreased significantly in CCl4 treated mice given hAEC. These mice had significantly lower hepatic protein levels of the chemokine monocyte chemoattractant protein-1 than mice given CCl4 alone. Alternatively activated M2 macrophages are associated with fibrosis resolution. CCl4 treated mice given hAEC showed increased expression of genes associated with M2 macrophages including YM-1, IL-10 and CD206. We provide novel data showing that hAEC transplantation induces a wound healing M2 macrophage phenotype associated with reduction of established hepatic fibrosis that justifies further investigation of this potential cell-based therapy for advanced hepatic fibrosis.

Therapeutic effects of human amniotic epithelial cell transplantation on double-transgenic mice co-expressing APPswe and PS1ΔE9-deleted genes

Human amniotic epithelial cells (HAECs), which exhibit characteristics of embryonic and pluripotent stem cells, could be utilized for cell therapy without legal or ethical problems. Double-transgenic (TG) mice (n=20) and wild-type (WT) mice (n=20) were randomly assigned to two groups, respectively. The transplantation group was treated with HAECs and the control group with PBS. A six-radial arm water maze was used to assess spatial memory. Immunofluorescence was utilized to track HAEC survival. Immunohistochemistry was used to determine octamer-binding protein 4 (oct-4) and nanog expression in the HAECs. High-performance liquid chromatography (HPLC) was used to measure acetylcholine levels in the hippocampus. The density of cholinergic neurons in the basal forebrain and nerve fibers in the hippocampus was measured following acetylcholinesterase staining. Results showed that transplanted HAECs survived for at least eight weeks and migrated to the third ventricle without immune rejection. Graft HAECs also expressed the specific stem cell markers oct-4 and nanog. Compared with the control group, HAEC transplantation significantly ameliorated spatial memory deficits in TG mice, as well as increased acetylcholine levels and the number of hippocampal cholinergic neurites. Intracerebroventricular HAEC transplantation improved spatial memory in double-TG mice, and results suggested that increased acetylcholine levels in the hippocampus, released by surviving cholinergic neurites, were responsible for this improvement.

A comparative study on rabbit bone mesenchymal stem cells and human amniotic epithelial cells transplantation for rabbit limbal stem cell deficiency

Background Limbal stem cell deficiency usually leads to blindness, and traditional therapy is limited. Recent research demonstrated that bone mesenchymal stem cells ( BMSCs ) and human amniotic epithelial cells(AECs) could differentiate into many kinds of cells including corneal epithelial cells, but the outcome and effect of these cells on corneal stem cell deficiency are still unclear. Objective This study aimed to observe and compare the effects of rabbit BMSCs and human AECs transplantation for rabbit limbal stem cell deficiency. Methods Eighteen clean New Zealand rabbits were randomly divided into the amniotic stroma(AS) group, rabbit BMSCs group and human AECs group with 6 rabbits for each group. Limbal stem cell deficiency models were established by putting a piece of filter paper that had been soaked in a NaOH solution at the corneal center. Rabbit BMSCs were isolated and purified by density gradient centrifugation combined with the attachment culture method, and human AECs were collected by a sequential trypsin digestion technique,and the third generation rabbit BMSCs and the first generation human AECs were identified with RT-PCR. After that,cells were inoculated onto the denuded AS and grafted to the corneal surface of the experimental animals. Twenty-eight days after cell transplantation, the therapeutic effects were evaluated based on the corneal neovascularization and opacity scores. Corneal histopathological examination and immunohistochemistry were performed to evaluate and compare the effectiveness among AS,rabbit BMSCs and human AECs on corneal stem cell deficiency. The procedure complied with the Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. Results The third generation of rabbit BMSCs grew well after 12 hours, and the first generation of human AECs formed a membrane-like monolayer after 48 hours of incubation on AS. Immunohistochemistry staining showed that, 28 days after transplantation, the surface cells of the cornea were positive for cytokeratin 3 in both the rabbit BMSCs group and human AECs group.Compared with the AS group,the corneal neovascularization and opacity grades were significantly decreased in the rabbit BMSCs group( Z=-2. 983, P =0. 003 ; Z =-2. 844, P =0. 004 ) and human AECs group ( Z =-2. 817, P =0. 005 ; Z =-2.041, P =0. 041 ). Histopathological analysis exhibited that stratified corneal epithelial-like cells formed on the corneal stroms 28 days after grafting and no signs of goblet cells and neovascularization were found. Less inflammatory cells and regular collagen fiber could be seen in the rabbit BMSCs group and human AECs group. In addition,clinical observation also revealed that the corneas were much clearer in the rabbit BMSCs group than the human A ECs group( Z =-2. 091 , P=0. 037 ), but the corneal neovascularization score was similar between them (Z = -0. 267,P=-0. 789). Conclusions Rabbit BMSCs and human AECs can differentiate into corneal epithelial-like cells on the damaged corneal surface and further demonstrate remarkable inhibitory effects on corneal neovascularization and inflammatory cells. The more dominant and prominent effect is the role played by rabbit BMSCs in the improvement of corneal transparency. Key words: Bone mesenchymal stem cell;  Amniotic epithelial cell;  Limbal stem cell;  Corneal neovascularization; Stem cell transplantation

An experimental study on intracerebroventricular transplantation of human amniotic epithelial cells in a rat model of Parkinson's disease

Objectives: Human amniotic epithelial (HAE) cells are formed from amnioblasts, separated from the epiblast at about the eighth day after fertilization. In the present study, we attempt to investigate the effects of intracerebroventricular transplantation of HAE cells on Parkinson's disease (PD) rats.Methods: A PD rat model was induced by 6-OHDA injections. Then the rats were transplanted intracerebroventricularly with HAE cells. Apomorphin-induced turns were used to assess the neurobehavioral deficit in rats. Immunofluorescence cytochemistry was used to track the survival of HAE cells. Tyrosinehydroxylase (TH) immunohistochemistry was used to determine the density of TH-positive cells in rat substantia nigra and the differentiation of HAE cells. High performance liquid chromatography (HPLC) was used to measure the levels of dopamine (DA) and its metabolites 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum. HVA levels in the cerebrospinal fluid of rats were also determined by HPLC.Results: The results showed that transplanted HAE cells can survive for at least 10 weeks and differentiate into TH-positive cells in PD rats. The grafts significantly ameliorated apomorphine-induced turns in PD rats. TH immunohistochemistry showed that HAE cells attenuated the loss of TH-positive cells in rat substantia nigra. In addition, HAE cells prevented the fall of DA and its metabolites DOPAC and HVA in PD rats. Increased HVA levels in the cerebrospinal fluid of PD rats were also observed.Conclusion: These results demonstrate that HAE cells have beneficial effect on 6-OHDA-induced PD rats, which may be due to the neurotrophic factors secrete by HAE cells.

An effect of transplantation of human amniotic epithelial cells on Parkinson disease model rats

Objective To investigate the survival time of human amniotic epithelial cells(HAECs) after being transplanted into the lateral ventricle of Parkinson disease (PD) model rats,and the effect of HAECs on the circling behavior.MethodsThe Parkinson model was made by using stereotactic microinjection of 6-hydroxydopamine(6-OHDA) into the cerebral striatum.51 PD models were randomly divided into three groups:the HAECs group,the phosphate buffer saline(PBS) group and the normal model group.The HAECs survival expression was investigated in the fifth week by using human specific monoclone antibody nestin and vimentin.After being treated for 10 weeks,the influence of HAECs on the substantia nigra's tyrosine hydroxylase (TH) positive cells of all three groups was collected.Finally,the contents of dopamine (DA)and its metabolite dihydroxyphenylacetic acid(DOPAC) and homovanillic acid(HVA) in the striatum were tested with high performance liquid chromatography-electrochemical detection after being treated for 10 weeks.Results The HAECs can survive for 10 weeks after being transplanted into the lateral ventricle of the PD model rats.The circling behavior of the HAECs group significantly ameliorated than the PBS group and normal model group(P≤0.01).The TH immunohistocbemistry showed that the TH positive cells of HAECs group increased than PBS group and normal model group(P≤0.01).The content of DA,HVA and DOPAC of HAECs group increased than PBS group(P＜0.05～0.01).In addition,the content of DA in the eerebrospinal fluid of HAECs group increased than PBS group(P≤0.01).Conclusions The human amniotic epithelial cells transplantation can improve the cycling behavior of the PD models rats.It may be due to the content of increased DA and its metabolite in the striatum of PD models rats. Key words: Human amniotic epithelial cells; Parkinson disease;  Models,animal;  Cell transplantation; Dopamine

Transplantation of human amniotic epithelial cells improves hindlimb function in rats with spinal cord injury

Human amniotic epithelial cells (HAECs), which have several characteristics similar to stem cells, therefore could possibly be used in cell therapy without creating legal or ethical problems. In this study, we transplanted HEACs into the injured spinal cord of rats to investigate if the cells can improve the rats' hindlimb motor function. HAECs were obtained from a piece of fresh amnion, labeled with Hoechst33342, and transplanted into the site of complete midthoracic spinal transections in adult rats. The rats (n = 21) were randomly divided into three groups: Sham-operation group (n = 7), cells-graft group (n = 7), and PBS group (n = 7). One rat of each group was killed for histological analysis at the second week after the transplantation. The other six rats of each group were killed for histological analysis after an 8-week behavioral testing. Hindlimb motor function was assessed by using the open-field BBB scoring system. Survival rate of the graft cells was observed at second and eighth weeks after the transplantation. We also detected the myelin sheath fibers around the lesions and the size of the axotomized red nucleus. A one-way ANOVA was used to compare the means among the groups. The significance level was set at P < 0.05. The graft HAECs survived for a long time (8 weeks) and integrated into the host spinal cord without immune rejection. Compared with the control group, HAECs can promote the regeneration and sprouting of the axons, improve the hindlimb motor function of the rats (BBB score: cells-graft group 9.0 +/- 0.89 vs PBS group 3.7 +/- 1.03, P < 0.01), and inhibit the atrophy of axotomized red nucleus [cells-graft group (526.47 +/- 148.42) microm(2) vs PBS group (473.69 +/- 164.73) microm(2), P < 0.01]. Transplantation of HAECs can improve the hindlimb motor function of rats with spinal cord injury.

Role of human amniotic epithelial cell transplantation in spinal cord injury repair research

Human amniotic epithelial cells (HAEC) possess certain properties similar to that of neural and glial cells. In the present work, the potential of HAEC as stem cells for spinal cord injury repair was tested. HAEC obtained from human placenta were labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethyllindocarbocyanine perchlorate (Dil) in the culture medium. These labeled cells were transplanted into the transection cavities in the spinal cord of bonnet monkeys. Results were analyzed after 15 and 60 days of post-transplantation. HAEC cells survived in the monkey spinal cord for up to the maximum period of observation in the present study, i.e. 60 days. HAEC graft was penetrated by the host axons. There was no glial scar at the transection lesion site. Some of the host spinal neurons and axons were labeled with Dil (used to label HAEC) whereas in lesion control group, there was no such host-neuron labeling. This may be either due to the prevention of death in the axotomized neuron’s ensuing lesion or due to the neurotrophic effect exhibited by the transplanted HAEC. Further studies would be required to verify these speculations. Therefore from this pilot study it appears that HAEC survive in the transplanted environment, support the growth of host axons through them, prevent the formation of glial scar at the cut ends and may prevent death in axotomized cells or attract the growth of new collateral sprouting. The abovementioned properties, i.e. serving as a suitable milieu for the host axons to grow, preventing glial scar at the lesion site and rescuing axotomized neurons from death were previously reported in the case of neural transplantation studies. Thus it is speculated that HAEC may be having certain properties equal to the beneficial effects of neural tissue in repairing spinal cord injury. Apart from this speculation, there are two more reasons for why HAEC transplantation studies are warranted to understand the long-term effects of such transplantations. First, there was no evidence of immunological rejection probably due to the non-antigenic nature of the HAEC. Second, unlike neural tissue, procurement of HAEC does not involve many legal or ethical problems.