DEVELOPMENT OF CELLULAR CARDIOMYOPLASTY METHODS

Heart failure is becoming a major public health problem, and considering the increased longevity rates of the world population, it is expected to be the prevailing cardiac disease of the century. When this disease becomes refractory to pharmacological therapy, available surgical treatment, that appears the most radical, is the replacement of the entire failing organ, as in cardiac transplantation. However the technique has some limitations inherent to the procedure, such as organ shortage and graft vasculopathy. In this setting, over these past years, cellular transplantation has emerged as an attractive alternative therapy for severe heart failure.

Electropulse supports research efforts to find new methods of stem cell use as a plastic material for cardiac disease treatment and to create a stem cell bank for damaged heart tissue reconstruction.

The objective of cellular cardiomyoplasty method development is the estimation of the capability of stem cells of different genesis to be a cardioplastic material.

The first stage of the development was a study of stem cells obtained from newborn rat hearts in the capacity of a plastic material for coronary heart disease (CHD) treatment.

Owing to the absence of culture technologies typically used for growing of stem cell mass required for a reparation, we made a decision to work with a "natural" material - rich in stem cells, newborn rat hearts.

At this stage the tasks were:

• Building of the optimal model for stem cells testing; and identification of reparation markers.
• Development of methods to obtain stem cells from newborn rat hearts.
• Determination of the optimal time and the effective dose for a stem cell injection.
• Development of stem cell cryopreservation techniques.

The second stage was a study of stem cells obtained from adipose tissue in the capacity of a plastic material for CHD treatment.

The most promising source of autologous stem cells in adult organisms is adipose tissue. It can be easily obtained under a local anesthetic (liposorption) with minimal discomfort for patients unlike in case of bone marrow. Besides adipose tissue has higher number of stem cells than hemopoietic tissue and can provide enough of the plastic material.

However this technique requires a tissue culture laboratory and special reagents and mediums.

At the second stage the tasks were:

• Development of methods to obtain and grow stem cells from adipose tissue.
• Determination of the optimal time and the effective dose for a stem cell injection.
• Development of stem cell cryopreservation techniques.

The third stage was designing of a device for stem cell delivery into a damaged myocardium and its experimental application.

The fourth stage was application of the cardioplasty method to clinical praxis including the following actions.

• Study of stem cell use as a plastic material for cardiac disease treatment.
• Document preparation for an application for patent for the "cell cryopreservation medium".
• Conduction of experiments for the development of CHD modeling methods in rats. The modeling was performed by left ventricle coronary artery ligation for testing of stem cell ability for myocardium reconstruction.
• Development of new technology for the obtaining of the cell fraction with high percentage of blast cells (stem cells pertain to blast cell category). This technology comprises 18 steps of purification and separation. Cell vitality amounted 95%, number of blast elements - 85%, cellularity - 4,3х10⁶/ml.
• Part of material was cryopreserved.

A clinical trial is now underway to determine the effective dose for a stem cell injection in rats with CHD for myocardium reparation.