You are here

| Bone Marrow Stem Cells

Stem Cells that Stick Around Aid Heart Repair

Comment

Discuss

Review of “Injection of Human Cord Blood Cells with Hyaluronan Improves Postinfarction Cardiac Repair in Pigs” from Stem Cells Translational Medicine by Stuart P. Atkinson

Stem cell-based strategies to treat myocardial infarction (MI) often opt for autologous bone marrow mononuclear cells (BM-MNCs) to promote repair and regeneration. However, some studies suggest that MNCs from older and unhealthy patients, those more likely to suffer from heart attacks, have a low reparative/regenerative potential [1]. Couple this with the low heart retention rates observed after transplantation into the myocardium of hearts in animal models, and the chance of MNCs fulfilling their regenerative potential fall even further.

To get round these problems, researchers from the laboratory of Patrick C.H. Hsieh and Shiaw-Min Hwang have assessed if human umbilical cord blood mononuclear cells (CB-MNC) combined within a hyaluronan (HA)-based hydrogel to promote myocardial retention can increase heart repair after MI in a mini-pig model. Their new study, published in Stem Cells Translational Medicine, demonstrates that this new combination strategy significantly improves heart performance and may represent a new strategy to treat ischemic heart diseases [2].

Initial assessments in the pig heart following MI found that while CB-MNC injection alone had the ability to prevent loss of the myocardium compared to the vehicle control, only upon the addition of HA did systolic and diastolic functions both improve. Hemodynamic analysis also demonstrated the need for both HA and CB-MNCs to improve both diastolic and systolic function, and this combination also significantly decreased the infarct size and prevented heart dilatation.

But was this improved function due to an increase in CB-MNC retention? After labelling cells with a fluorescent marker, the researchers found that the addition of HA maintained a larger number of cells in the injected area (See figure – CB-MNCs labelled with red fluorescent dye) and they noted signs of human cell retention even after two months. This increased cell retention correlated with enhanced angiogenesis and arteriogenesis and the differentiation of CB-MNCs into endothelial cells but not smooth muscle cells.

Previous studies have found that UC-MNCs have a clinically relevant therapeutic potential [3] and this study demonstrates that this effect, combined with the cell retention effects of HA, can mediate enhanced cardiac reparative effects. The use of UC-derived cells will negate any possibility of age-related deficits in function and are a potentially attractive clinical alternative to BM-derived cells. How will they compare in a side-by-side comparison with BM-MNCs? Hopefully further studies will unravel this answer and point to an improved therapeutic option for an all too prevalent ailment.

References

  1. Heeschen C, Lehmann R, Honold J, et al. Profoundly reduced neovascularization capacity of bone marrow mononuclear cells derived from patients with chronic ischemic heart disease. Circulation 2004;109:1615-1622.
  2. Chang MY, Huang TT, Chen CH, et al. Injection of Human Cord Blood Cells With Hyaluronan Improves Postinfarction Cardiac Repair in Pigs. Stem Cells Transl Med 2015;
  3. Pimentel-Coelho PM, Rosado-de-Castro PH, da Fonseca LM, et al. Umbilical cord blood mononuclear cell transplantation for neonatal hypoxic-ischemic encephalopathy. Pediatr Res 2012;71:464-473.