Blood vessel obstruction deprives tissues of life-giving oxygen and leads to the death of cells. If enough cells within a tissue die, the organ in which whose tissues reside could experience organ failure.
To quote the Sound of Music, “How does one solve a problem like blood vessel obstruction?” The obvious answer is to make new blood vessels to replace the blocked ones. Scientists have identified growth factors that are important in blood vessel formation during development. Therefore, injecting these growth factors should lead to the formation of new blood vessels, right? Unfortunately, such a strategy does not work very well (see Collison and Donnelly, Eur J Vasc Endovasc Surg 2004 28:9-23). Therefore, vascular specialists have focused on the ability of stem cells make new blood vessels, and this approach has yielded some very definite successes.
During development, the same stem cell gives rise to blood vessels and blood cells. This stem cell, the hemangioblast is found in a structure known as the yolk sac (even though it never functions as a yolk sac). In the yolk sac, during the third week of development, little specs form called “blood islands. These blood islands are small clusters of hemangioblasts with the cells at the center of the cluster forming blood cells and the cells at the periphery of the blood island forming blood vessels.
In adults, blood cell-making stem cells are found in the bone marrow. Blood vessel-making stem cells are endothelial progenitor cells or EPCs can be rather easily isolated from peripheral blood, however they are thought to originate from bone marrow. EPCs are not a homogeneous group of cells. There are different types with different surface molecules found in different locations.
Recently another cell from circulating blood called an “endothelial colony forming cell” or ECFC has been discovered, and this cell can attach to uncoated plastic surfaces in a growth medium. These cells can be grown to high numbers, even though it takes a rather long time to expand them. Once the ECFC culture system is further perfected, ECFCs will be excellent candidates for therapeutic trials (Reinisch et al., Blood 2009 113: 6716-25).
Fat tissue is also a reservoir of EPCs and mesenchymal stem cells. Fat-based mesenchymal stem cells help induce blood vessel formation and stimulate fat-based EPCs form blood vessels. Because of this remarkable “one-two punch” in fat, with cells that stimulate blood vessel formation and cells that actually form blood vessels, fat is a source of blood vessel-forming cells that can be used for therapeutic purposes.
Several pre-clinical experiments and presently ongoing clinical trials have examined the ability of fat-based stems to treat patients with conditions that result from insufficient circulation to various tissues. In rodents, experimental obstruction of the blood vessels in the hindlimb create a condition called “hindlimb ischemia.” In a rodent model of hindlimb ischemia, human fat-based stem cell applications not only improve the use of the limb and decrease limb damage, but also induce the formation of new blood vessels that definitely come from the applied stem cells (Miranville, et al., Circulation 2004 110: 349-55; Planat-Bernard, et al., Circulation 2004 109: 656-63 & Moon et al., Cell Physiol Biochem 2006 17: 279-90). Several clinical trials have been conducted with bone marrow-based EPCs for limb-based ischemia in humans, and these trials have been largely successful(see Szoke and Brinchmann, Stem Cells Translational Medicine 2012: 658-67 for a list of these trials). Adding mesenchymal stem cells from fat might improve the results of these trials.
In the heart, obstructed blood vessels can cause intense chest pain, a condition known as “angina pectoris.” EPCs have been used in clinical trials to treat patients with angina pectoris, and these trials have all been successful and have all used EPCs from bone marrow. These experiments, despite their success, have used bone marrow-based cells that were not fractionated and EPCs are less than 1% of the total number of cells. Also, the vast majority of cells introduced into heart migrate into the lungs, spleen and other organs. Also, those cells that remain tend to die off. A way to improve the survival of these implanted cells might be to combine them with mesenchymal stem cells from fat with EPCs from fat. Presently, the MyStromalCell trial is underway to test the efficacy of fat-based stem cells on the heart.
Fat provides an incredible treasure-trove of healing cells that have been demonstrated in animal experiments to relieve tissue ischemia and generate new blood vessels (for a summary of pre-clinical experiments in laboratory animals, see Qayyum AA, et al., Regen Med. 2012 May;7(3):421-8). Clinical trials with these cells are also underway. We have almost certainly only begun to tap to potential of these exciting cells that can be extracted so easily for our bodies.