PMID- 33246489 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20210618 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 11 IP - 1 DP - 2020 Nov 27 TI - Potentiation of cord blood cell therapy with erythropoietin for children with CP: a 2 x 2 factorial randomized placebo-controlled trial. PG - 509 LID - 10.1186/s13287-020-02020-y [doi] LID - 509 AB - BACKGROUND: Concomitant administration of allogeneic umbilical cord blood (UCB) infusion and erythropoietin (EPO) showed therapeutic efficacy in children with cerebral palsy (CP). However, no clinical studies have investigated the effects of UCB and EPO combination therapy using a 2 x 2 four-arm factorial blinded design with four arms. This randomized placebo-controlled trial aimed to identify the synergistic and individual efficacies of UCB cell and EPO for the treatment of CP. METHODS: Children diagnosed with CP were randomly segregated into four groups: (A) UCB+EPO, (B) UCB+placebo EPO, (C) placebo UCB+EPO, and (D) placebo UCB+placebo EPO. Based on the UCB unit selection criteria of matching for >/= 4/6 of human leukocyte antigen (HLA)-A, -B, and DRB1 and total nucleated cell (TNC) number of >/= 3 x 10(7)/kg, allogeneic UCB was intravenously infused and 500 IU/kg human recombinant EPO was administered six times. Functional measurements, brain imaging studies, and electroencephalography were performed from baseline until 12 months post-treatment. Furthermore, adverse events were closely monitored. RESULTS: Eighty-eight of 92 children enrolled (3.05 +/- 1.22 years) completed the study. Change in gross motor performance measure (GMPM) was greater in group A than in group D at 1 month ( big up tri, open2.30 vs. big up tri, open0.71, P = 0.025) and 12 months ( big up tri, open6.85 vs. big up tri, open2.34, P = 0.018) post-treatment. GMPM change ratios were calculated to adjust motor function at the baseline. Group A showed a larger improvement in the GMPM change ratio at 1 month and 12 months post-treatment than group D. At 12 months post-treatment, the GMPM change ratios were in the order of groups A, B, C, and D. These results indicate synergistic effect of UCB and EPO combination better than each single therapy. In diffusion tensor imaging, the change ratio of fractional anisotropy at spinothalamic radiation was higher in group A than group D in subgroup of age >/= 3 years. Additionally, higher TNC and more HLA-matched UCB units led to better gross motor outcomes in group A. Adverse events remained unchanged upon UCB or EPO administration. CONCLUSIONS: These results indicate that the efficacy of allogeneic UCB cell could be potentiated by EPO for neurological recovery in children with CP without harmful effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01991145 , registered 25 November 2013. FAU - Min, Kyunghoon AU - Min K AD - Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, Gyeonggi-do, Republic of Korea. AD - Rehabilitation and Regeneration Research Center, CHA University, Seongnam, Republic of Korea. FAU - Suh, Mi Ri AU - Suh MR AD - Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, Gyeonggi-do, Republic of Korea. FAU - Cho, Kye Hee AU - Cho KH AD - Rehabilitation and Regeneration Research Center, CHA University, Seongnam, Republic of Korea. AD - Department of Rehabilitation Medicine, CHA Ilsan Medical Center, CHA University School of Medicine, Ilsan, Republic of Korea. FAU - Park, Wookyung AU - Park W AD - Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, Gyeonggi-do, Republic of Korea. AD - Rehabilitation and Regeneration Research Center, CHA University, Seongnam, Republic of Korea. FAU - Kang, Myung Seo AU - Kang MS AD - Department of Laboratory Medicine, CHA Bundang Medical Center, CHA University School of Medicine and CHA Cord Blood Bank, Seongnam, Republic of Korea. FAU - Jang, Su Jin AU - Jang SJ AD - Department of Nuclear Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea. FAU - Kim, Sang Heum AU - Kim SH AD - Department of Radiology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea. FAU - Rhie, Seonkyeong AU - Rhie S AD - Department of Pediatrics, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea. FAU - Choi, Jee In AU - Choi JI AD - Rehabilitation and Regeneration Research Center, CHA University, Seongnam, Republic of Korea. FAU - Kim, Hyun-Jin AU - Kim HJ AD - Rehabilitation and Regeneration Research Center, CHA University, Seongnam, Republic of Korea. FAU - Cha, Kwang Yul AU - Cha KY AD - CHA Hollywood Presbyterian Medical Center, Los Angeles, CA, USA. FAU - Kim, MinYoung AU - Kim M AUID- ORCID: 0000-0001-5481-2985 AD - Department of Rehabilitation Medicine, CHA Bundang Medical Center, CHA University School of Medicine, 59 Yatap-ro, Bundang-gu, Seongnam, Gyeonggi-do, Republic of Korea. kmin@cha.ac.kr. AD - Rehabilitation and Regeneration Research Center, CHA University, Seongnam, Republic of Korea. kmin@cha.ac.kr. LA - eng SI - ClinicalTrials.gov/NCT01991145 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20201127 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - 11096-26-7 (Erythropoietin) SB - IM MH - Cell- and Tissue-Based Therapy MH - *Cerebral Palsy MH - Child MH - Child, Preschool MH - Diffusion Tensor Imaging MH - *Erythropoietin MH - Fetal Blood MH - Humans PMC - PMC7694426 OTO - NOTNLM OT - Cerebral palsy OT - Clinical trial OT - Erythropoietin OT - Functional performance OT - Umbilical cord blood COIS- The authors declare no potential conflicts of interest. EDAT- 2020/11/29 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/11/27 CRDT- 2020/11/28 05:23 PHST- 2020/05/06 00:00 [received] PHST- 2020/11/06 00:00 [accepted] PHST- 2020/11/28 05:23 [entrez] PHST- 2020/11/29 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/11/27 00:00 [pmc-release] AID - 10.1186/s13287-020-02020-y [pii] AID - 2020 [pii] AID - 10.1186/s13287-020-02020-y [doi] PST - epublish SO - Stem Cell Res Ther. 2020 Nov 27;11(1):509. doi: 10.1186/s13287-020-02020-y.