4.6 Article

Injection of Human Cord Blood Cells With Hyaluronan Improves Postinfarction Cardiac Repair in Pigs

Journal

STEM CELLS TRANSLATIONAL MEDICINE
Volume 5, Issue 1, Pages 56-66

Publisher

WILEY
DOI: 10.5966/sctm.2015-0092

Keywords

Human cord blood cells; Hyaluronan; Myocardial infarction; Pig model

Funding

  1. National Science Council [NSC102-2314-B-006-067-MY3, NSC102-2321-B-001-069-MY3]
  2. National Health Research Institutes [NHRI-EX103-10026SI]
  3. Academia Sinica Translational Medicine Program

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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 (Ml+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.

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