Vein transplantation using human umbilical cord blood stem cells in the treatment of stroke sequela

BACKGROUND: Transplanted mononuclear cell (MNC) of umbilical blood can survive in central nervous system (CNS) of host through blood brain barrier, differentiate into nerve cells, migrate to damaged site and integrate morphological structure and function with nerve cells of host so as to improve deficiencies of sensatory function, motor function and cognitive function and influence on stroke sequela. OBJECTIVE: To observe the vein transplantation of human umbilical cord blood stem cells (HUCBSC) for improving neurological function, limb function and activity of daily living of patients with stroke and evaluate the reliability. DESIGN: Self-controlled study. SETTING: Department of Neurosurgery, the Second People's Hospital of Zhengzhou City; Red-crossed Blood Center of Henan Province; Department of Neurosurgery, the Fist Affiliated Hospital of Zhengzhou University. PARTICIPANTS: A total of 10 patients with stroke sequela were selected from Department of Cerebral Surgery, the Second People's Hospital of Zhengzhou City from April to December 2005. There were 9 males and 1 female aged from 35 to 75 years with the mean age of 56 years. All of them were diagnosed with CT and MRI examination and coincidence with diagnostic criteria of stroke established by the Fourth National Academic Meeting for Cerebrovascular Disease. All patients provided informed consent. METHODS: 80-140 mL umbilical blood of term birth of newborn was selected hermetically and maintained in sterile plastic bag. And then, the blood was centrifugated at the speed of 1 500 r/min for 30 minutes at 22 ℃ in order to separate MNC, i.e., HUCBSC. In addition, after final diagnosis during hospitalization, stroke patients were perfused with HUCBSC through superficial vein of back of the hand. Each patient was averagely perfused with 6 portions of HUCBSC (cellular numbers ≥ 1×108/portion) and the interval between each portion was 1-7 days with the mean interval of 4 days. MAIN OUTCOME MEASURES: ① Neurological function of stroke patients was evaluated with neurological function deficiency (NFD) before treatment and at 3 months after treatment. The scale includes consciousness, level fix function, facial paralysis, language, muscle force of upper limbs, muscle force of lower limb and step function. The total scores ranged from 0 to 45; meanwhile, the lower the scores were, the better the neurological function was. ② Motor function of injured limbs was evaluated with Fugl-Meyer Assessment (FMA), including motor function of upper limbs, motor function of lower limbs, balance ability, sensory function and motion of joint. The total scores ranged from 0 to 226; meanwhile, the higher the scores were, the better the motor function of limbs was. ③ Activities of daily living (ADL) was evaluated with Barthel Index (BI), including having meals, taking a bath, dressing oneself, putting on clothes, walking in balance and stair activity. The total scores ranged from 0 to 100; meanwhile, the higher the scores were, the stronger the ADL was. RESULTS: A total of 10 patients were involved in the final analysis. After treatment, NFD of stroke patients was (10.9±5.09) points, which was lower than that before treatment [(25.4±6.09) points, t =8.213, P < 0.01]. In addition, after treatment, FMA and BI of stroke patients were (80.9±25.00) points and (81.1±15.93) points, respectively, which were higher than those before treatment [(31.9±21.85) points, (36.2±19.41) points, t =13.024, 13.670, P < 0.01]. Immuno-suppressive drugs were not used during the whole therapeutic procedure; moreover, immunological rejection and allergic reaction were not observed during the same period. CONCLUSION: Transplanting HUCBSC through superficial vein of back of the hand is regarded as a simple and safe method for the treatment of stroke sequela.

Editor's Choice——Umbilical cord blood mesenchymal stem cell differentiation and transplantation in neural regeneration

Previous in vivo experiments have shown that human umbilical cord blood mesenchymal stem cells can promote the proliferation and differentiation of damaged celts, and help to repair damaged sites, Recent studies have reported that umbilical cord blood-derived mesenchymal stem cells can differentiate into neurons and glial cells. Recent studies have reported that the repair mechanisms underlying cord blood stern cells involve the replacement of damaged cells and mediation of the local micro-environment.

The chimeric mice derived from umbilical cord blood stem cells of EGFP-transgenic mouse

Objective:The chimeric mice were prepared by microinjection of blastocyst cavity using umbilical cord blood stem cells(UCBSCs)of Enhanced Green Fluorescent Protein(EGFP)-transgenic mouse,which was expected to provide a theoretical and experimental basis for the study of in-vivo differentiation of adult stem cells.Methods:Mouse UCBSCs expressing green fluorescence was microinjected into blastocyst cavity and several blastocysts were transferred into uterus of pseudo pregnant mouse.First of all,new-born candidate chimeric mice were observed through feather color.Secondly,the genomic DNA and total RNA were extracted to analyze chimeric rate in several tissues.Finally,flow cytometry was used to detect percentage of green fluorescent cells mice in several tissues.Results:The UCBSCs expressing green fluorescent protein were successfully isolated.After flow cytometry analysis,the proportion of cells expressing green fluorescence was 80.25%.Through microinjection and embryo transfer,we got five white new-born mice and no chimeric feather color was observed.The analyses of PCR and RT-PCR were carried out to detect EGFP gene using six tissues including heart muscle,liver,lung,skin,leg muscle and adipose tissue.The results showed that the leg muscle and adipose tissue of two mice were positive and the other tissues and six tissues of the other 3 mice were all negative.The leg muscle and adipose tissue of two positive mice were digested into single-cells suspension and were carried out flow cytometry analysis.The results showed that the average chimeric rates of leg muscle and adipose tissue of two positive mice were 9.87% and 5.78%,respectively.Conclusions:The results demonstrated that adult UCBSCs could differentiate into leg muscle and adipose tissue in vivo.

Combined use of Y-tube conduits with human umbilical cord stem cells for repairing nerve bifurcation defects

Given the anatomic complexity at the bifurcation point of a nerve trunk,enforced suturing between stumps can lead to misdirection of nerve axons,thereby resulting in adverse consequences.We assumed that Y-tube conduits injected with human umbilical cord stem cells could be an effective method to solve such problems,but studies focused on the best type of Y-tube conduit remain controversial.Therefore,the present study evaluated the applicability and efficacy of various types of Y-tube conduits containing human umbilical cord stem cells for treating rat femoral nerve defects on their bifurcation points.At 12 weeks after the bridging surgery that included treatment with different types of Y-tube conduits,there were no differences in quadriceps femoris muscle weight or femoral nerve ultrastructure.However,the Y-tube conduit group with longer branches and a short trunk resulted in a better outcome according to retrograde labeling and electrophysiological analysis.It can be concluded from the study that repairing a mixed nerve defect at its bifurcation point with Y-tube conduits,in particular those with long branches and a short trunk,is effective and results in good outcomes.

The impact of HLA haplotype and alleles mismatches of donor-recipient pairs on outcome of haplo-identical hematopoietic stem cell transplantation with a third part cord blood unit

Objective To analyze allele mismatches of HLA-A,-B,-C,-DRB1,-DQB1 and haplotype mismatch of donor-recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit.Methods 230 pairs of donor-recipient were performed HLA-A,B,C,DRB1,DQB1 typing using

Successful transplantation of double unit umbilical-cord blood from unrelated donors in high risk leukemia with a long follow-up

Umbilical-cord blood (UCB) is a source of hematopoietic stem cells that has been successfully used for transplantation, primarily in children. But the low cell dose severely limits the application of unrelated umbilical-cord blood transplantation (UCBT) in adult patients, particularly in those with high body weight. We hypothesized that the combined transplantation of two partially matched UCB units would improve engraftment without crossed immunological rejection. Since May 2000, six adult patients with high risk leukemia have been transplanted in this study.