Cord Blood Cells Make New Blood Vessels

Cytotherapy, November 2nd, 2009

Cord blood is known to contain large numbers of stem cells. Currently, it is used as an alternative to bone marrow transplantation for certain conditions. Advantages of cord blood over bone marrow include the fact that it does not need to be as closely matched between donor and recipient as bone marrow does, and additionally, because the cord blood stem cells are younger, theoretically they should be more potent at re-establishing production of blood cells after a transplant.

In conventional cord blood transplants, which are usually performed for conditions such as leukemias, the immune system of the recipient is destroyed in order to allow the donor cord blood cells to engraft. Additionally, by providing large doses of chemotherapy, not only is the recipient immune system destroyed but many of the leukemic cells are also killed. The widespread use of cord blood in treatment of leukemias has led to a dogma being generated that cord blood transplants are useless when used for other treatments. Essentially, most hematologists believe that if a cord blood transplant is performed without prior treatment of the recipient with chemotherapy/immune suppressants, then one of two things will happen. The cord blood cells will either attack the recipient, a process called graft versus host disease, or conversely, the recipient immune system cells will destroy the cord blood cells, a process called host versus graft.

The current dogma, however, appears to be wrong. Firstly, cord blood administration has been performed in thousands of patients without adverse effects in absence of immune suppression. Why would someone administer cord blood for reasons besides stem cell transplants? Originally, cord blood was used as an alternative source of blood when adult blood shortages existed. The unique property of cord blood is that it contains fetal hemoglobin, which is much more effective at transporting oxygen than adult hemoglobin. Secondly, human cord blood has been used without suppression of the immune system in animal studies for conditions such as type I diabetes, ALS, and Parkinson's Disease. The apparent ability of cord blood to induce therapeutic effects suggests that the cells were not rejected. Scientists at the Institute for Cellular Medicine have used cord blood derived cells in treatment of heart failure, which was described in a publication (Ichim et al. Placental mesenchymal and cord blood stem cell therapy for dilated cardiomyopathy. Reprod Biomed Online. 2008 Jun;16(6):898-905). The scientific rational for how cord blood stem cells may be administered without graft versus host or host versus graft reactions is provided in a paper written by the Institute for Cellular Medicine and Medistem, which is freely available at http://www.translational-medicine.com/content/5/1/8 .

A paper published today (Finney et al. Umbilical cord blood-selected CD133(+) cells exhibit vasculogenic functionality in vitro and in vivo. Cytotherapy. 2009 Nov 2.) from the Mary Laughlin's group describes the use of cord blood cells in creation of new blood vessels. Several conditions would benefit from the creation of new blood vessels, for example, in diseases such as ischemic heart disease or peripheral artery disease, the body tries to make new blood vessels in order to compensate for occlusion in the existing blood vessels. Unfortunately, the body cannot make enough new blood vessels to keep up with demand. If cord blood stem cells could be used to make new blood vessels, this treatment would have numerous applications.

In the publication, the researchers describe that cord blood contains a higher number of cells expressing the CD133 marker. These are cells that on the one hand can make new blood cells (called hematopoietic stem cells), but have also been postulated by others to have the ability to generate the cells that line the blood vessels (endothelial cells).

By culturing purified cord blood CD133 cells with existing blood vessel cells outside of the body, the scientists found that the CD133 cells would increase the rate at which the blood vessel cells multiplied. Using this knowledge, the next question was whether the CD133 cells could stimulate formation of new blood vessels in animal models.

One of the major arteries that feeds the leg, called the femoral artery, was blocked in order to mimic conditions of decreased blood flow. Usually this results decreased function of the leg and death of muscle tissue. Administration of CD133 cells was shown to stimulate new blood vessel formation, preserve leg function, and decrease the amount of cell death in the digits of the mouse limbs. Activity of CD133 cells derived from cord blood seemed to be higher than that of bone marrow derived cells.

These studies suggest that cord blood derived stem cells may be therapeutically useful in conditions requiring formation of new blood vessels. In fact, a company called Medistem actually has filed patents on the use of drugs already approved for other indications in order to modify umbilical cord blood to increase potency in the stimulation of new blood vessels in patients with critical limb ischemia, an advanced form of peripheral artery disease.