• Change of Medical research council [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the MRC (Medical research council) scale between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences. [0, 1, 2, 2, 2+, 3-, 3, 3+, 4, 5] (The higher values represent a better outcome.)
• Change of National Institutes of Health Stroke Scale [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the NIHSS (National Institutes of Health Stroke Scale) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.[0~42] (The lower values represent a better outcome.)
• Change of Manual Function Test [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the MFT (Manual Function Test) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.[0~32 for each arm] (The higher values represent a better outcome.)
• Change of Fugl-Meyer Assessment [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the FMA (Fugl-Meyer Assessment) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.[0~66 for each arm] (The higher values represent a better outcome.)
• Change of Berg Balance Scale [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the BBS (Berg Balance Scale) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.[0~56] (The higher values represent a better outcome.)
• Change of Trunk Imbalance Scale [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the TIS (Trunk Imbalance Scale) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.[0~23] (The higher values represent a better outcome.)
• Change of Korean Mini Mental State Exam [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the K-MMSE (Korean Mini Mental State Exam) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences. [0~30] (The higher values represent a better outcome.)
• Change of Korean Wechsler adult intelligence scale-IV [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the K-WAIS-IV (Korean Wechsler adult intelligence scale-IV) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.[The total score is a standard score with a mean of 100 and a standard deviation of approximately 15.] (The higher values represent a better outcome.)
• Change of Korean version of the Western Aphasia Battery [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the K-WAB (Korean version of the Western Aphasia Battery) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.[0~100] (The higher values represent a better outcome.)
• Change of Brain imaging [ Time Frame: baseline - 6 months ]
  The difference in the Brain imaging (Basic brain MRI, functional brain MRI, diffusion tensor imaging brain MRI) between the three groups at baseline, and 180 days was confirmed by comparing differences.
• Change of Biomarkers [ Time Frame: baseline - 1 day - 15 days - 1 month - 3 months - 6 months ]
  The difference in the Biomarkers (TGFβ, IL-10, IL-8, PTX3, PCNT,...) between the three groups at baseline, 1 day, 15 days, 30 days, 90 days and 180 days was confirmed by comparing differences.

• Change of Medical research council [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the MRC (Medical research council) scale between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.
• Change of National Institutes of Health Stroke Scale [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the NIHSS (National Institutes of Health Stroke Scale) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.
• Change of Manual Function Test [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the MFT (Manual Function Test) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.
• Change of Fugl-Meyer Assessment [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the FMA (Fugl-Meyer Assessment) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.
• Change of Berg Balance Scale [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the BBS (Berg Balance Scale) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.
• Change of Trunk Imbalance Scale [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the TIS (Trunk Imbalance Scale) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.
• Change of Korean Mini Mental State Exam [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the K-MMSE (Korean Mini Mental State Exam) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.
• Change of Korean Wechsler adult intelligence scale-IV [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the K-WAIS-IV (Korean Wechsler adult intelligence scale-IV) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.
• Change of Korean version of the Western Aphasia Battery [ Time Frame: baseline - 3 months - 6 months ]
  The difference in the K-WAB (Korean version of the Western Aphasia Battery) between the three groups at baseline, 90 days, and 180 days was confirmed by comparing differences.
• Change of Brain imaging [ Time Frame: baseline - 6 months ]
  The difference in the Brain imaging (Basic brain MRI, functional brain MRI, diffusion tensor imaging brain MRI) between the three groups at baseline, and 180 days was confirmed by comparing differences.
• Change of Biomarkers [ Time Frame: baseline - 1 day - 15 days - 1 month - 3 months - 6 months ]
  The difference in the Biomarkers (TGFβ, IL-10, IL-8, PTX3, PCNT,...) between the three groups at baseline, 1 day, 15 days, 30 days, 90 days and 180 days was confirmed by comparing differences.

UCB is a high-quality source of mesenchymal stem cells, and studies are being actively developed for stroke patients. UCB therapy has a neuroprotective effect through anti-inflammatory effect and anti-apoptosis.

However, UCB alone has not been able to provide sufficient improvement and is being studied for combination therapies with growth factors that can exert its effects. Among the various growth factors, EPO is a powerful factor that can act as a neurotrophic factor in neurons, astrocytes, oligodendrocytes, microglia, endothelial cells, and neural stem/precursor cells.

In our previous study of subacute stroke animal models, investigators confirmed that the combined administration of UCB and EPO improved the behavioral assessment (mNSS, Cylinder test) compared to UCB only administration.

The aim of this study is to investigate the difference in therapeutic effects between UCB alone therapy and UCB and EPO combination therapy.

• Stroke
• Umbilical Cord Blood
• Erythropoietin
• Safety
• Treatment Outcome

• Drug: Umbilical cord blood infusion
  The umbilical cord blood is donated umbilical cord blood which is stored in the cord blood bank donated by Cha Hospital. The total number of nuclear cells should be at least 2 x 10 7 / kg, and at least three out of six of the six human leukocyte antigens (HLA-A, B, DR) should be selected. The cord blood that matches ABO and Rh blood type is preferentially used. Umbilical cord blood infusion is administered intravenously and is performed at the stem cell clinical trial center. The procedure is performed by the doctor who is enrolled in this study. Monitor pulse and oxygen saturation during the procedure.
  Other Name: UCB
• Drug: Erythropoietin injection
  Recombinant human erythropoietin is used and is administered intravenously at a maximum of 5 times at a rate of 500 IU / kg 2 times/week after cord blood peripheral blood infusion, calculated as the dose per body weight. Or subcutaneous administration if intravenous administration is not possible. Store in a sealed container at 2-8 °C in the refrigerator before dosing. Erythropoietin injection is performed at the stem cell clinical trial center. The procedure is performed by the doctor who is enrolled in this study. Monitor pulse and oxygen saturation during the procedure.
  Other Name: EPO
• Drug: Placebo umbilical cord blood infusion
  Placebo umbilical cord blood infusion is administered intravenously and is performed at the stem cell clinical trial center. The procedure is performed by the doctor who is enrolled in this study. Monitor pulse and oxygen saturation during the procedure.
  Other Name: pUCB
• Drug: Placebo erythropoietin injection
  Placebo erythropoietin injection is performed at the stem cell clinical trial center. The procedure is performed by the doctor who is enrolled in this study. Monitor pulse and oxygen saturation during the procedure.
  Other Name: pEPO
• Procedure: Active rehabilitation
  Physical therapy and occupational therapy are performed daily.
  Other Name: Rehabilitation

• Experimental: UCB infusion and EPO injection group
  Take immunosuppressant agents for 1 week. Umbilical cord blood is administered in the treatment room. Afterward, the venous erythropoietin agent injects into the peripheral vein 5 times a total of 5 times a week.
  Interventions:

  • Drug: Placebo umbilical cord blood infusion
  • Drug: Placebo erythropoietin injection
  • Procedure: Active rehabilitation
• Experimental: UCB infusion and placebo EPO injection group
  Take immunosuppressant agents for 1 week. Umbilical cord blood is administered in the treatment room. Afterward, the venous erythropoietin placebo injects into the peripheral vein 5 times a total of 5 times a week.
  Interventions:

  • Drug: Umbilical cord blood infusion
  • Drug: Placebo erythropoietin injection
  • Procedure: Active rehabilitation
• Placebo Comparator: Placebo UCB infusion and placebo EPO injection group
  Take immunosuppressant placebo for 1 week with the same schedule as the experimental group. As in the experimental group, placebo umbilical cord blood is administered in the treatment room and stay in the treatment room for the same time. Afterward, the venous erythropoietin placebo injects into the peripheral vein 5 times a total of 5 times a week. Other inspection schedules proceed with other groups.
  Interventions:

  • Drug: Umbilical cord blood infusion
  • Drug: Erythropoietin injection
  • Procedure: Active rehabilitation

Inclusion Criteria:

1. Adult patients over 20 years old
2. Patients with a stroke lasting from 30 days to less than 9 months
3. After hearing and fully understanding the details of this clinical trial, the person or legal representative has agreed to voluntary participation and has agreed in writing to comply with the notice

Exclusion Criteria:

Patients with one or more of the following can not participate in the study.

1. Patients with uncontrolled hypertension
2. A person who has impaired ability of consent, who is not accompanied by a guardian
3. Women who are pregnant, lactating, have a pregnancy plan during the trial, or those who do not use an available contraceptive method (women of childbearing age must be negative in the pregnancy test on baseline visit (0 weeks) .)

4. Those who satisfy the following conditions

   • A person whose ALT / AST is measured at 120 IU / L or more
   • Serum creatinine greater than 1.8 mg / dL
   • Total bilirubin> 1.8 mg / dL
   • Total WBC count less than 3000 / mm3
   • Those with a Hb of 16 g / dL or more
   • Platelet count less than 150,000 / uL or more than 675,000 / uL
5. Clinically significant infections during the screening period (pneumonia, pyelonephritis, sepsis, etc.)
6. Persons with severe medical conditions such as cardiovascular, digestive, respiratory, and endocrine conditions.
7. Any kind of confirmed congenital or acquired immune deficiency syndrome
8. Those who have been diagnosed with malignant carcinoma (excluding complete remission for more than 10 years)

9. If participants have side effects on your medication [Regarding erythropoietin agent]

   • Patients with hypersensitivity to erythropoietin
   • Patients sensitive to mammalian cell-derived drugs or human albumin
   • epileptic patients
   • Patients with a history of seizures
   • Patients on a thrombolytic drug (meaning thrombolytic agent such as Tissue Plasminogen Activator, allowing anti-platelet agents such as aspirin and plavix) [Related to tacrolimus] Patients with hypersensitivity to tacrolimus or macrolide compounds
   • Patients receiving cyclosporine or bosentan
   • Patients receiving potassium-preserving diuretics
10. Other If the investigator determines that participation in this trial is not appropriate