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Cord blood angiogenic progenitor cells are decreased in bronchopulmonary dysplasia. Baker Christopher D,Balasubramaniam Vivek,Mourani Peter M,Sontag Marci K,Black Claudine P,Ryan Sharon L,Abman Steven H The European respiratory journal Bronchopulmonary dysplasia (BPD), the chronic lung disease of prematurity, is associated with impaired vascular and alveolar growth. Antenatal factors contribute to the risk for developing BPD by unclear mechanisms. Endothelial progenitor cells, such as angiogenic circulating progenitor cells (CPCs) and late-outgrowth endothelial colony-forming cells (ECFCs), may contribute to angiogenesis in the developing lung. We hypothesise that cord blood angiogenic CPCs and ECFCs are decreased in preterm infants with moderate and severe BPD. We quantified ECFCs and the CPC/nonangiogenic-CPC ratio (CPC/non-CPC) in cord blood samples from 62 preterm infants and assessed their relationships to maternal and perinatal risk factors as well as BPD severity. The CPC/non-CPC ratio and ECFC number were compared between preterm infants with mild or no BPD and those with moderate or severe BPD. ECFC number (p<0.001) and CPC/non-CPC ratio (p<0.05) were significantly decreased in cord blood samples of preterm infants who subsequently developed moderate or severe BPD. Gestational age and birth weight were not associated with either angiogenic marker. Circulating vascular progenitor cells are decreased in the cord blood of preterm infants who develop moderate and severe BPD. These findings suggest that prenatal factors contribute to late respiratory outcomes in preterm infants. 10.1183/09031936.00017312
Phase I-II Clinical Trial Assessing Safety and Efficacy of Umbilical Cord Blood Mononuclear Cell Transplant Therapy of Chronic Complete Spinal Cord Injury. Zhu Hui,Poon Waisang,Liu Yansheng,Leung Gilberto Ka-Kit,Wong Yatwa,Feng Yaping,Ng Stephanie C P,Tsang Kam Sze,Sun David T F,Yeung David K,Shen Caihong,Niu Fang,Xu Zhexi,Tan Pengju,Tang Shaofeng,Gao Hongkun,Cha Yun,So Kwok-Fai,Fleischaker Robert,Sun Dongming,Chen John,Lai Jan,Cheng Wendy,Young Wise Cell transplantation Umbilical cord blood-derived mononuclear cell (UCB-MNC) transplants improve recovery in animal spinal cord injury (SCI) models. We transplanted UCB-MNCs into 28 patients with chronic complete SCI in Hong Kong (HK) and Kunming (KM). Stemcyte Inc. donated UCB-MNCs isolated from human leukocyte antigen (HLA ≥4:6)-matched UCB units. In HK, four patients received four 4-μl injections (1.6 million cells) into dorsal entry zones above and below the injury site, and another four received 8-μl injections (3.2 million cells). The eight patients were an average of 13 years after C5-T10 SCI. Magnetic resonance diffusion tensor imaging of five patients showed white matter gaps at the injury site before treatment. Two patients had fiber bundles growing across the injury site by 12 months, and the rest had narrower white matter gaps. Motor, walking index of SCI (WISCI), and spinal cord independence measure (SCIM) scores did not change. In KM, five groups of four patients received four 4-μl (1.6 million cells), 8-μl (3.2 million cells), 16-μl injections (6.4 million cells), 6.4 million cells plus 30 mg/kg methylprednisolone (MP), or 6.4 million cells plus MP and a 6-week course of oral lithium carbonate (750 mg/day). KM patients averaged 7 years after C3-T11 SCI and received 3-6 months of intensive locomotor training. Before surgery, only two patients walked 10 m with assistance and did not need assistance for bladder or bowel management before surgery. The rest could not walk or do their bladder and bowel management without assistance. At about a year (41-87 weeks), WISCI and SCIM scores improved: 15/20 patients walked 10 m ( p = 0.001) and 12/20 did not need assistance for bladder management ( p = 0.001) or bowel management ( p = 0.002). Five patients converted from complete to incomplete (two sensory, three motor; p = 0.038) SCI. We conclude that UCB-MNC transplants and locomotor training improved WISCI and SCIM scores. We propose further clinical trials. 10.3727/096368916X691411
Human umbilical cord blood mononuclear cells protect against renal tubulointerstitial fibrosis in cisplatin-treated rats. Li Xu-Wei,Feng Li-Xin,Zhu Xue-Jing,Liu Qian,Wang Hong-Shen,Wu Xi,Yan Ping,Duan Xiang-Jie,Xiao Ye-Qing,Cheng Wei,Peng Jin-Cheng,Zhao Fei,Deng Ying-Hao,Duan Shao-Bin Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Currently, there is no effective method to prevent renal interstitial fibrosis after acute kidney injury (AKI). In this study, we established and screened a new renal interstitial fibrosis rat model after cisplatin-induced AKI. Our results indicated that rats injected with 4 mg/kg cisplatin once a week for two weeks after firstly administrated with 6.5 mg/kg loading dose of cisplatin could set up a more accurate model reflecting AKI progression to renal interstitial fibrosis. Then, we investigated the effects and possible mechanisms of human umbilical cord blood mononuclear cells (hUCBMNCs) on renal tubular interstitial fibrosis after cisplatin-induced AKI. In rats injected with hUCBMNCs for four times, level of matrix metalloproteinase 7 (MMP-7) in serum and urine, urinary albumin/creatinine ratio, tubular pathological scores, the relative collagen area of the tubulointerstitial region, endoplasmic reticulum dilation and the mitochondrial ultrastructural damage were significantly improved. The level of reactive oxygen species, α-smooth muscle actin (α-SMA), [NOD]-like pyrin domain containing protein 3 and cleaved-Caspase 3 in renal tissue decreased significantly. However, in rats injected with hUCBMNCs for two times, no significant difference was discovered in MMP-7 levels and urinary albumin/creatinine ratio. Although expression of α-SMA and the percentage areas of collagen staining in tubulointerstitial tissues were ameliorated in rats injected with hUCBMNCs for two times, the effects were significantly weaker than those in rats injected with hUCBMNCs for four times. Taken together, our study constructed a highly efficient, duplicable novel rat model of renal fibrosis after cisplatin-induced AKI. Multiple injections of hUCBMNCs may prevent renal interstitial fibrosis after cisplatin-induced AKI. 10.1016/j.biopha.2019.109662