title: Injection of Human Cord Blood Cells With Hyaluronan Improves Postinfarction Cardiac Repair in Pigs.
abstract: Recent clinical trials using autologous bone marrow or peripheral blood cells to treat myocardial infarction (MI) show controversial results, although the treatment has a good safety profile. These discrepancies are likely caused by factors such as aging, systemic inflammation, and cell processing procedures, all of which might impair the regenerative capability of the cells used. Here, we tested whether injection of human cord blood mononuclear cells (CB-MNCs) combined with hyaluronan (HA) hydrogel improves cell therapy efficacy in a pig MI model. A total of 34 minipigs were divided into 5 groups: sham operation (Sham), surgically induced-MI plus injection with normal saline (MI+NS), HA only (MI+HA), CB-MNC only (MI+CB-MNC), or CB-MNC combined with HA (MI+CB-MNC/HA). Two months after the surgery, injection of MI+CB-MNC/HA showed the highest left ventricle ejection fraction (51.32%±0.81%) compared with MI+NS (42.87%±0.97%, p<.001), MI+HA (44.2%±0.63%, p<.001), and MI+CB-MNC (46.17%±0.39%, p<.001) groups. The hemodynamics data showed that MI+CB-MNC/HA improved the systolic function (+dp/dt) and diastolic function (-dp/dt) as opposed to the other experimental groups, of which the CB-MNC alone group only modestly improved the systolic function (+dp/dt). In addition, CB-MNC alone or combined with HA injection significantly decreased the scar area and promoted angiogenesis in the infarcted region. Together, these results indicate that combined CB-MNC and HA treatment improves heart performance and may be a promising treatment for ischemic heart diseases.
  
  
  CONCLUSIONS
  This study using healthy human cord blood mononuclear cells (CB-MNCs) to treat myocardial infarction provides preclinical evidence that combined injection of hyaluronan and human CB-MNCs after myocardial infarction significantly increases cell retention in the peri-infarct area, improves cardiac performance, and prevents cardiac remodeling. Moreover, using healthy cells to replace dysfunctional autologous cells may constitute a better strategy to achieve heart repair and regeneration.
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan, Republic of China Institute of Clinical Medicine, and National Cheng Kung University, Tainan, Taiwan, Republic of China.
authors.forename: Ming-Yao
authors.initials: MY
authors.lastname: Chang
authors.affiliation: Institute of Clinical Medicine, and National Cheng Kung University, Tainan, Taiwan, Republic of China Department of Life Science, National Cheng Kung University, Tainan, Taiwan, Republic of China.
authors.forename: Tzu-Ting
authors.initials: TT
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors.forename: Chien-Hsi
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors.forename: Bill
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Bioresource Collection and Research Center, Food Industry Research and Development Institute, Hsinchu, Taiwan, Republic of China phsieh@ibms.sinica.edu.tw hsm@firdi.org.tw.
authors.forename: Shiaw-Min
authors.initials: SM
authors.lastname: Hwang
authors.affiliation: Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan, Republic of China Institute of Clinical Medicine, and National Cheng Kung University, Tainan, Taiwan, Republic of China Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China Division of Cardiovascular Surgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Republic of China phsieh@ibms.sinica.edu.tw hsm@firdi.org.tw.
authors.forename: Patrick C H
authors.initials: PC
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D036101:Cord Blood Stem Cell Transplantation; D064593:Heterografts; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020100:Hydrogels / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000628:therapy*; D009206:Myocardium; D012038:Regeneration / Q000187:drug effects*; D013552:Swine; D013556:Swine, Miniature
chemical_list: D020100:Hydrogels; D006820:Hyaluronic Acid
keywords: Human cord blood cells; Hyaluronan; Myocardial infarction; Pig model