As an advanced form of peripheral artery disease, critical limb ischemia (CLI) results in approximately 100,000 amputations every year in the United States alone. It is often seen in diabetics and is a major cause both of morbidity and of mortality, with approximately 20 to 45% of all patients requiring amputation, after which death within the first year is estimated to be as high as 45%. The quality of life in such patients is extremely low, compared by some doctors to that of terminal cancer patients.
In the past, treatment options for patients with CLI have been extremely limited, and without notable success. Now, however, the company Medistem, Inc., has developed a treatment for CLI which uses the powerful endometrial regenerative cells (ERCs) which Medistem brought to international attention last year.
Previous, independent clinical trials have shown some improvement in CLI patients who received autologous (in which the donor and recipient are the same person) stem cells that were either derived from the patient’s own bone marrow or mobilized from peripheral blood. Similarly, ERCs, which are adult stem cells that are derived from menstrual blood and which resemble mesenchymal stem cells (MSCs), are believed to be associated with endometrial angiogenesis and have been shown to have powerful angiogenic properties. Additionally, ERCs contain an exceptionally high level of growth factors and are notable for a wide variety of other impressive properties which include their ability to inhibit the inflammatory response, their ease of expandability in large quantities without incurring a loss of differentiability nor any karyotypic abnormalities, and the fact that ERCs are highly immune privileged and therefore do not trigger immune rejection.
In the recently published study, which was led by the vascular surgeon Dr. Michael Murphy, a group of mice was divided into 8 who were treated for CLI with ERCs, and 8 mice who served as the “controls” and whose CLI was untreated. Following ligation of the femoral artery and its branches in each of the mice, which thereby induced CLI, the 8 mice who were chosen to be treated were each administered approximately 1 million ERCs intramuscularly. By day 14, necrosis was observed in the legs of the 8 “control” mice, who did not receive the ERCs, while the 8 mice who were treated with the ERCs still had intact limbs. Especially striking was the absence of any immune rejection of the ERCs, despite the fact that these were human stem cells, which were administered to mice which had fully competent immune systems.
It has already been known for some time that MSCs exhibit immune modulatory properties, both in vitro and in vivo. For example, the company Osiris Therapeutics is currently involved in Phase III clinical trials with allogeneic MSCs that are derived from bone marrow and which are currently being tested as treatment for two diseases, namely, graft-versus-host disease, and Crohn’s disease. Now, in the study conducted by Dr. Murphy, Medistem has demonstrated the ability of ERCs to prevent limb loss in an animal model of critical limb ischemia, even with animals that were fully immune competent. ERCs are therefore believed to offer what is known as cytokine mediated angiogenesis, which thus far has been especially effective as a therapy for CLI in this particular animal model.
Medistem, which has pioneered the development of ERCs as a “universal donor” product, has received global recognition for its work in this field, including the “Publication of the Year” award for 2007, recognizing its discovery of ERCs, which was awarded to Medistem at London’s Royal Society of Medicine in early 2008. Medistem is now seeking to use ERCs as a therapy for patients who are at risk of amputation due to CLI.