Preserving Heart Tissue After a Heart Attack: Umbilical Cord-Coated Stem Cell Spheres

Eliana Martinez and her colleagues from the laboratories of Chuen Lee and Theo Kofidis at the National University of Singapore have published an extremely interesting paper in the journal Stem Cells and Development. In this paper, Martinez and her colleagues use a novel approach to deliver stem cells to the hearts of rats after a heart attack.

Usually, stem cells are given to heart attack patients in one of several ways. In laboratory animals, it is common to simply inject the stem cells directly into the heart muscle. This is done after the animals’ chest has been cut open. This procedure, known as a thoracotomy, is feasible in human patients, but unless the patient is undergoing coronary artery graft bypass surgery, cracking the chest leaves the patients in severe pain, greatly weakened, and with a very long recovery period. Therefore, unless necessary, this procedure is not preferred. Secondly, stem cells are delivered through the coronary arteries by means of the same technology used to deliver stents (percutaneous coronary intervention or PCI). In this case the cells are delivered through the coronary arteries while the arteries are propped open. This procedure is relatively easy to perform and no special equipment or training is required to deliver the cells, but several studies have shown that only a fraction of the cells make it to the heart muscle. The third technique uses direct injection into the heart muscle without cracking the patient’s chest. This technique uses special injection devices under the direction of sophisticated heart imaging technologies. Special equipment and specialized training is required to deliver the cells. Only a few centers offer this mode of delivery. The cells are well retained in the heart muscle, but a percentage of them leak out and find their way into the lung and other organs.

All of these techniques have their ups and downs. To that end, Martinez and her colleagues decided to deliver small spheres of stem cells surrounded by umbilical cord cells. These subamnion-cord-lining mesenchymal stem cell angiogenic spheroids (say that fast five times) consist of a special cell type from human umbilical cord called human umbilical cord vein endothelial cells or HUVECs that were used to encase another type of umbilical cord stem cell called cord-lining mesenchymal stem cells or CL-MSCs.

CL-MSCs have been evaluated in the laboratory and they seem to possess a robust ability to evade detection by the immune system and suppress inflammation, and do a better job of inducing healing than bone marrow-based stem cells (see Deuse T, et al., Cell Transplant. 2011;20(5):655-67). These cells also showed a marked ability to repair the heart after a heart attack (see Lilyana and others, Tissue Eng Part A 19:1303-1315).

To this end, Kofidis and his co-workers decided to use the spheroid technique because stem cells grown in liquid suspension and not flat culture dishes seem to do a better job of holding onto their healing properties than stem cell grown under standard conditions. Next, Martinez and others added HUVEC cells, which make blood vessels, the encase the CL-MSCs. Once they spheroids were made, they used fibrin (the protein found in blood clots) to paste the spheroids to the heart tissue after inducing a heart attack in laboratory rats.

These spheroids were mercifully called SASGs, since the proper name of these clusters was subamnion-cord mesenchymal stem cells angiogenic spheroids embedded within fibrin grafts (exhale). The laboratory animals were either given fibrin grafts without SASGs, neither fibrin grafts nor SASGs, and SASGs while the animal had its chest cracked, SASGs delivered without a thoracotomy (under video-assisted thoracoscopic surgery, and fibrin grafts under with no SASGs without have the chest cracked open.

In both cases in which SASGs were delivered, the structure and function of the heart improved in every physiological category examined. The heart beat more efficiently, the heart scar was smaller, there were more blood vessels, less, cell death, less sign of heart failure,

Even though this was a relatively small study in laboratory animals, it shows that a minimally invasive procedure can deliver stem cells to the heart that will stay in the heart and deliver healing to it,

This strategy should be expanded to larger numbers of animals and then, if it still statistically pans out, larger animal model systems should be examined (e.g., minipigs).   This is an ingenious technique, and hopefully, other laboratories will confirm the efficacy of this technique and the robust healing capabilities of this particular stem cell type from umbilical cord.