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Posts Tagged ‘heart regeneration’

New treatment for AMI

Posted in Cardiac muscle regeneration, Stem Cells for Regenerative Medicine, Tissue Engineering and Regenerative Medicine, tagged , on November 21, 2015| Leave a Comment »

New treatment for AMI

Larry H. Bernstein, MD, FCAP, Curator

LPBI

 

Combining Umbilical Cord Cells with Hyaluronic Acid Improves Heart Repair After a Heart Attack

November 20, 2015 by
https://beyondthedish.wordpress.com/2015/11/20/combining-umbilical-cord-cells-with-hyaluronic-acid-improves-heart-repair-after-a-heart-attack/

Umbilical cord blood cells have an advantage over bone marrow or peripheral blood cells in that aging, systemic inflammation, and stress or damage caused by cell processing procedures can potentially compromise and diminish the regenerative capability of these cells. This problem is particularly acute in the case of treating patients who have recently suffered a heart attack, since transplanted cells experience a rather hostile environment that kills off most cells. Additionally, blood flow through the heart tends to wash out infused cells, which further decreases any regenerative activities the cells might have otherwise exerted.

With this in mind, Patrick Hsieh and his colleagues at the Academia Sinica, in Taipei, Taiwan tested if ability of human cord blood mononuclear cells (CB-MNCs) injected into the heart in combination with a hyaluronan (HA) hydrogel could extend the regenerative abilities of these cells in a pig model. HA is a common component of connective tissue, and, in general, it is very well tolerated by patients and implanted cells. Furthermore, it has the added bonus of shielding cells from a hostile environment and preventing them from being washed out of the heart.

Hsieh used a total of 34 minipigs and divided them into five different groups. One group was the sham operation group in which minipigs received surgical incisions but no heart attack was induced. The second group had heart attacks surgically induced and received infusions of normal saline solutions. The third group of minipigs also experienced heart attacks, and had HA injected into the heart walls. The fourth group also suffered heart attacks and received injections of human umbilical cord stem cells into their heart walls. The fifth group experienced heart attacks and received injections of both HA and human umbilical cord blood cells. The animals were kept and examined two months after surgery.

Two months after the surgery, the minipigs that received injections of human umbilical cord blood cells plus HA showed the highest left ventricle ejection fraction (51.32% ± 0.81%). This is significant when compared to 42.87% ± 0.97%, for the group that received injections of normal saline, 44.2% ± 0.63% for the group that received injections of HA alone, and 46.17% ± 0.39% for the group that received injections of umbilical cord blood cells only. Additionally, hearts from minipigs that received cord blood cells plus HA improved the systolic and diastolic function significantly better than the other experimental groups. Injections of either cord blood cells alone or in combination with HA significantly decreased the scar area and promoted the formation of new blood vessels in the infarcted region. In general, this study suggests that combined infusion of umbilical cord blood cells and HA improves the function of the heart after a heart attack and might prove to be a promising treatment option of heart attack patients.

This is a preclinical study, but it is a preclinical study in a larger animal model system. Umbilical cord blood cells have a demonstrated ability to induce healing in the heart after a heart attack. However, the combination of these cells with HA almost certainly significantly increases cell retention in the heart, thereby significantly improving cardiac performance, and preventing cardiac remodeling. Therefore, using healthy cells donated from another source to replace damaged or moribund cells may be a better option to treat a heart patient and repair their sick heart.

This work appeared in Stem Cells Trans Med November 2015, http://dx.doi.org:/10.5966/sctm.2015-0092. 

 

Enabling Technologies for Cell-Based Clinical Translation:Injection of Human Cord Blood Cells With Hyaluronan Improves Postinfarction Cardiac Repair in Pigs

Ming-Yao Chang, Tzu-Ting Huang, Chien-Hsi Chen, Bill Cheng, Shiaw-Min Hwang, Patrick C.H. Hsieh

Stem Cells Trans Med first published on November 16, 2015;doi:10.5966/sctm.2015-0092  

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

 Although safe, recent clinical trials using autologous bone marrow or peripheral blood cells to treat myocardial infarction (MI) show controversial results. 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.

Significance

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.

 

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