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.

There are several types of stem cell therapy that are in development. They can be broadly broken down into cells that come from the same patient, called autologous, and cells that derived from another source, called allogeneic. Autologous stem cells have the advantage not causing worries regarding immune rejection. Unfortunately, in many conditions that require stem cell therapy, such as peripheral artery disease, or coronary heart disease, the original stem cell pool in the patient is depleted. This is because on the one hand the body is constantly using the stem cells to try to heal itself, and on the other hand, there is an underlying inflammation in the conditions mentioned that suppress stem cell activity. Therefore, in some situations it is better to use "fresh" stem cells from another donor.

Mesenchymal stem cells can be extracted from bone marrow, fat, and several other sources. In contrast to the current dogma (which appears to be scientifically incorrect) that stem cells that make blood can not be transplanted without immune suppression, the current thinking for mesenchymal stem cells is that immune suppression is not needed when they are transplanted. Part of the reason for this is that mesenchymal stem cells have been published in many papers to actually "immune modulate". In other words, mesenchymal stem cells appear to have the ability to reprogram the immune system so as to not destroy them, but at the same time they allow the immune system to continue performing its usual function of destroying pathogens.

In a recent paper (Chin et al. Cryopreserved mesenchymal stromal cell treatment is safe and feasible for severe dilated ischemic cardiomyopathy. Cytotherapy. 2009 Nov 2) the use of mesenchymal stem cells was evaluated after the cells have been stored frozen. The importance of this is that an ideal stem cell treatment would be a "universal donor" stem cell "drug" in that cells could be shipped to the point of care frozen and used in the convenience of a doctor’s office, without the need for expensive equipment that is currently a requirement in the medical practice of stem cell therapy.

In the publication the scientists treated three patients with dilated cardiomyopathy with mesenchymal stem cells that were previously frozen. Stem cells were injected directly into the heart muscle as the patients were undergoing coronary artery bypass surgery. All three patients responded better than what would have been expected had they undergone surgery alone in terms of cardiac function, ejection volume, and reduction of scarring. Although the study was uncontrolled and therefore efficacy data is not solid, the fact that the procedure was performed safely, without adverse effects at 1-year follow-up suggests that more studies need to be performed to evaluate efficacy of this approach.

The adult stem cell company Aldagen Inc, from Durham North Carolina announced today that it has filed a registration with the Securities Exchange Commission for an initial public offering with a potential value of $80.5 million. Details regarding price range or shares to be issues were not disclosed.

Aldagen is one of the adult stem cell companies in advanced clinical trials in the United States. The technology that they are developing is based on intellectual property covering the use of a specific enzyme, aldehyde dehydrogenase (ALDH), as a means of selecting stem cells with higher level of potency from adult sources. Although the particular type of stem cells that Aldagen is selecting for are stem cells that make blood, called hematopoietic stem cells, the company’s technology has been shown to select for other stem cells as well.

It’s most advanced program, is ALD-101, a purified cord blood stem cell product for treatment of inherited metabolic diseases in pediatric patients. This is in Phase III clinical trials, which means that the safety (Phase I) has been demonstrated, that preliminary efficacy (Phase II) has been demonstrated, and now what remains to be demonstrated is efficacy of the product in a double blind, placebo controlled study (Phase III). Several metabolic diseases have been successfully treated with stem cells from the cord blood. Conditions such as Krabbe Disease, involve defective biochemical pathways in cells that original from stem cells. By administration of new stem cells that express the correct biochemical and genetic components, the functioning cells end up taking over the function of the nonfunctioning cells.

The company is also preparing to conduct a Phase III clinical trial for critical limb using its product ALD-301. This product involves extraction of patient bone marrow, purification of cells expressing ALDH, and re-administration of the purified cells into the muscles of patients with critical limb ischemia. The rationale for this treatment is that patients with critical limb ischemia lack appropriate circulation in their legs and are at risk of amputation. By administration of the patient’s own stem cells, the cells are believed to stimulate the production of new blood vessels, which theoretically will reduce the need for amputation. Previous studies using stem cells for treatment of critical limb ischemia have demonstrated successful results in terms of improved walking distance and increased circulation (Kawamoto et al. Intramuscular Transplantation of Granulocyte Colony Stimulating Factor-Mobilized CD34-Positive Cells in Patients with Critical Limb Ischemia: A Phase I/IIa, Multi-Center, Single-Blind and Dose-Escalation Clinical Trial. Stem Cells. 2009 Aug 26), to our knowledge, the proposed Phase III trial will be the first FDA registration trial for use of stem cells in critical limb ischemia.

Additionally, Aldagen is developing ALD-201, which uses the patient’s own bone marrow derived stem cells, but instead of administering them into the ischemic leg, they are administered into the heart muscle by means of a specialized catheter. Currently ALD-201 completed a Phase I trial. In contrast to other cardiac clinical trials involving administration of stem cells after a heart attack, this is one of the few trials that is treating patients with chronic heart failure. Essentially the concept is that the stem cells will be able to create new blood vessels, which will help by providing more oxygen to the cardiac muscle, as well as stimulate stem cells that are resident in the heart through the production of various growth factors.

The company is performing several areas of investigation, including purification of cancer stem cells using their technique, as well as expansion into other disease conditions such as stroke and improvement of post-transplant reconstitution.

As with many biotechnology companies, Aldagen is not expected to be profitable in the close future. In the first nine months of 2009 the company spent 9.7 million, while a year ago it spent $13.8 million. The majority shareholder is Intersouth Partners, an early-stage venture capital who invests in companies in the South East US. Intersouth owns 41.6 percent of Aldagen. The underwriters of the IPO are Cowen and Co. and Wells Fargo Securities. A copy of the full S-1 filing may be obtained at the SEC website http://www.sec.gov/Archives/edgar/data/1128188/000119312509215575/ds1.htm