Michigan, has become a leader in the development of patient-specific multicellular therapies for the treatment of critical cardiac diseases. A key component of the company’s success is its proprietary, automated cell-processing system.
After a small amount of bone marrow is extracted from a patient’s hip during a brief outpatient procedure, the sample is subjected to Aastrom’s cell-processing technology to selectively and significantly expand naturally occurring populations of cell types that promote or facilitate healing. Through cell processing, the number of stem cells can be increased by as much as several hundred times more than the quantities found in the patient’s natural bone marrow. After 12 days of processing with the enhanced multicellular therapy (ixmyelocel-T), the cells are returned to the physician in a sterile bag to be administered within three days back into the same patient to stimulate regeneration of damaged cardiovascular tissue.
Aastrom’s manufacturing process is carried out in a highly automated, sterile environment that is fully protected and rigorously controlled through company protocols and current Good Manufacturing Practices guidelines mandated by the U.S. Food and Drug Administration. The cell-processing system operates in a 5,000-square-foot centralized manufacturing facility in Ann Arbor with an annual capacity to treat as many as 3,000 patients, as of May 2014. The system is designed to be easily reproduced and expanded based on future cell-processing production needs.
The cutting-edge manufacturing process works solely with adult stem cells derived from, and returned to, the same patient. The individualized therapeutic approach increases the likelihood that the cell therapy will integrate with surrounding tissues and reduce or eliminate the need for the patient to take immunosuppressive drugs.
Ixmyelocel-T Therapy
Ixmyelocel-T is a patient-specific, expanded multicellular therapy created using Aastrom’s unique cell-processing system. The therapy offers a number of features that are important for the success of treating patients suffering from complex, chronic diseases such as dilated cardiomyopathy (DCM), which is a widespread form of heart failure, and critical limb ischemia (CLI), the most severe form of peripheral arterial disease.
One of the most beneficial features of ixmyelocel-T is that it is autologous, meaning that it is specific to the individual patient. Starting with the patient’s own cells, which are already accepted by the patient’s immune system, enables the new healing-specific cells to integrate more seamlessly into existing tissues. As a result, the risk of rejection and the need for immunosuppressive therapy are virtually eliminated.
Cell expansion is another key advantage of ixmyelocel-T. With a patient bone marrow sample of just 50 milliliters (ml), critical stem cell types (mesenchymal cells, monocytes, and alternatively activated macrophages) can be expanded up to 300 times their original number present in the starting bone marrow sample. The larger cell quantities of multiple cell types aid in the process of tissue remodeling, immune response, and blood vessel formation to support cell function.
In addition to efficacy and safety evidence from U.S. clinical trials, ixmyelocel-T also offers the patient convenience because it is minimally invasive. Bone marrow can be extracted during an outpatient procedure lasting only about 15 minutes. The ixmyelocel-T therapy can be administered to the patient a few weeks later during a single outpatient procedure that can be completed in approximately 20 minutes.
Ixmyelocel-T Clinical Trials
Clinical trials of ixmyelocel-T have focused on therapies for DCM and CLI, which are two prevalent diseases associated with significant mortality and very limited treatment options.
Dilated cardiomyopathy is a progressive disease of the heart muscle in which the heart becomes enlarged. Heart enlargement causes poor function that often leads to progressive heart failure as the heart loses its ability to sufficiently contract and pump blood efficiently around the body. DCM is a leading cause of heart failure and heart transplantation. Some medication and medical devices can be used to help control DCM symptoms, but there is no cure for the disease.
Aastrom has been working to develop ixmyelocel-T as a potential cell-based therapy option for patients with DCM. As of 2014, the company’s clinical trials have focused on assessing the efficacy and safety of ixmyelocel-T administered by catheter and transendocardial injection and on evaluating the safety and tolerability of surgically delivered ixmyelocel-T compared to the traditional standard of care for patients with DCM.
Aastrom also has undertaken clinical trials for ixmyelocel-T as a treatment approach for critical limb ischemia, a severe form of peripheral arterial disease caused by chronic inflammatory processes in the arteries that hinder blood flow and reduce circulation to the legs, feet, and hands. Without sufficient blood supplies, the extremities become extremely painful, ulcers begin to form, and—without surgical revascularization procedures—tissue eventually begins to die. Sometimes amputation is the only way to stop the spread of tissue necrosis (tissue death), infection (from non-healing ulcers), or excruciating pain caused by CLI.
The company’s clinical trials for CLI have sought to assess the efficacy and safety of ixmyelocel-T treatment versus placebo in CLI patients generally and in regard to amputation-free survival at 12 months post-injection.
Cell Therapy Portfolio Expansion
On April 21, 2014, Aastrom Biosciences announced a definitive agreement to acquire Sanofi’s Cell Therapy and Regenerative Medicine business for $6.5 million. The acquisition gives Aastrom global commercial rights to manufacture and market three existing patient-specific cell therapy products: Carticel®, an implant marketed in the United States for the treatment of joint cartilage defects; MACI®, a third-generation joint implant therapy marketed in the European Union; and Epicel®, a permanent skin replacement available globally for the treatment of full-thickness burns covering 30 percent or more of total body surface area. Under the deal, Aastrom acquires global manufacturing and production centers in both the United States and Denmark.
Shari Parsons Miller
Independent Scholar
See Also: Clinical Trials, U.S.: Heart Disease; Clinical Trials, U.S.: Peripheral Vascular Disease; Heart Disease; Mesenchymal Stem Cells; Stem Cell Companies: Overview.
Further Readings
Johns Hopkins Medicine. “Stem Cell Therapy Safely Repairs Damaged Heart Muscle in Chronic Heart Failure Patients, Study Shows.” http://www.hopkinsmedicine.org/news/media/releases/stem_cell_therapy_safely_repairs_damaged_heart_muscle_in_chronic_heart_failure_patients_study_shows (Accessed May 2014).
Langwith, Jacqueline. “Stem Cells.” Detroit, MI: Gale Group, 2011.
Stein, Richard A. “ReGen Med: Straight Out of Mythology.” Genetic Engineering and Biotechnology News, v.3/12 (2013).
Adipose: Cell Types Composing the Tissue
Adipose: Cell Types Composing the Tissue
3
6
Adipose: Cell Types Composing the Tissue
Adipose tissue
