MEDICINE FOR ALL

To develop criteria that identify patients likely to benefit from regenerative therapies, it is important to identify functional indices associated with improved outcomes. Analysis from some trials support the importances of cell and patient characteristics in predicting clinical outcomes. In FOCUS-HF (First Bone Marrow Mononuclear Cell United States Study in Heart Failure) assessing effects of intramyocardial autologous bone marrow mononuclear cells in patients with no option chronic heart failure, younger patients (≤60 years)  had significantly higher numbers of mesenchimal progenitor cells  versus those >60 years. Younger patients also had significant improvement in maximal oxygen consumption (VO2 max) versus age-matched reference subjects while older patients did not, identifying age as an important modifier of therapeutic effect.

One solution is to use allogeneic cells from a therapeutically potent donor, but even optimal cells may not provide benefit if the recipient’s regenerative capacity is poor. It was suggested that although the focus in stem cells trials is typically on the administered  cells, there is little on the patient and tissue targeted for regeneration. Indeed, there is evidence that the variable cell potency observed across patients in clinical trials reflects not just the quality of delivered cells but also the underlying regenerative capacity of the treated patient. With the growing understanding that stem cell therapy functions to a large extent via paracrine  mechanisms, it seems clear that the recipient’s regenerative capacity is likely a critical determinant of therapeutic effect.

The majority of cardiac stem cell trials to date used autologous bone marrow stem cells. Yet, functional properties of bone marrow cells vary across patients, and comorbidities negatively affect cell characteristic. Chronic heart failure also negatively affect bone marrow cells function, with lower rates of colony formation units and response to erythropoetin stimulation versus age-matched controls. Although patients may receive the same number (ie. dose) of autologous bone marrow cells, the therapeutic potency of those  cells can vary widely from patient to patient, and this likely accounts, in part, for the observed variation in effect.

Stem cells therapy holds promise for chronic heart failure management as animal studies document that these cells modify local inflammatory conditions, release factors that stimulate angiogenesis and intrinsic tissue repair, modify adverse ventricular remodeling, and restore function. Clinical trials results, however, are more variable with some showing beneficial effects and other without. Preclinical studies are conducted in otherwise healthy animals, but clinical studies enroll chronic heart failure patients with multiple comorbidities (aging, diabetes mellitus,  hypertension, inflammation, etc) that negatively affect regenerative capacity. Significant variability in regenerative response is linked with variations in cell characteristics (eg. migratory and adhession capacity, clonogenicity, surface marker expression, and paracrine factor release). Using a personalized medicine approach (ie, tailoring treatment to patient characteristics to optimize benefit), the study propose to optimize cardiac cell therapy efficacy by prospectively selecting patients most likely to benefit using a cell potency assay to assess inheritent regenerative capacity.

medical illustration of the function of stem cells in the human body

How can I find out about clinical trials that use stem cells?

Ask your medical doctor for advice on what is available in your area for your disease or condition. Different clinical trials are offered at different institutions. Remember that the clinical trials have very strict entry critea to safeguard the safety of participants and to make sure that researchers will be able to answer their research question.

medical illustration of the function of stem cells in the human body

Should I get a second opinion?

You are encouraged to ask a lot of questions about the treatment being offered and to seek second opinions from independent qualified doctors. Your doctor should be supportive and help in the process of obtaining a second opinion. Medical records, research protocols, treatment protocols (where not well-established), and informed consent documents should be supplied to the person giving a second opinion.

medical illustration of the function of stem cells in the human body

What else should I ask?

Cost:

• What are the costs of the treatment? What does this include? What other costs will I incur?
• What would be the costs of emergency treatment if something goes wrong? Who would provide this and who would pay for this? Before traveling or agreeing to treatment, find out what costs your travel insurance, health insurance provider or national health program will cover, in what circumtances and in what countries.