Heart Muscle Regeneration

The adult heart lacks reserve cells and cannot regenerate. Thus, individuals who suffer a large acute myocardial infarction (heart attack) in which part of the myocardium (heart muscle) dies often descend into congestive heart failure that leads eventually to premature death.

Bioheart has three primary platforms for heart muscle regeneration and a multitude of combinations with other cells, proteins and agents such a growth factors and nitric oxide synthase. These three primary platforms are;

  1. Autologous skeletal muscle (satellite cells).

    The advantage of this technique is lack of immune response and convenience since the implanted cells are derived from the patient's thigh muscle. There are no ethical issues associated with this method.

    Research Partners: Doris Taylor, Ph.D., M.D., Duke University Medical Center, Syde Taheri, M.D. Millard Fillmore Hospital and University of Buffalo. Bioheart has an agreement to acquire exclusive rights to all heart muscle regeneration technologies developed by these laboratories and has entered into a forward research collaboration to bring these technologies to clinical practice.

    1. Results from the first ever experiments proving ability to improve myocardial performance in animal models were published by Doris Taylor of Duke University in Nature Medicine, Vol. 4, No. 8, August 1998. Dr. Taylor has continued her work adding growth factors and has found the combination of growth factors with myoblasts had 5:1 improvement over each injection on it's own. She is currently filing patent applications covering her related inventions.

    2. The injected cells connect end to end by intercalated discs (gap junctions) to show a phenotype more like cardiac myocytes at the periphery edge of scar tissue. Gap junctions have not been identified in the center area of treated scar tissue in animal experiments to date. All animal experiments have shown that treated areas beat in synchrony with surrounding heart muscle. The mechanism of synchronization is not fully understood at this time.

    3. Experiments indicated that immature skeletal myoblasts can be influenced by their surrounding microenvironment.

    4. In addition to improving myocardial performance and contractility in vivo, myoblast transplantation seemed to improve the diastolic pressure-strain relationship.

    5. Dr. Syde Taheri conducted a series of animal studies in 1998 confirming Dr. Taylor's results. Dr. Taheri has received two related patents and has a number pending.

    6. A number of other laboratories including Dr. Chiu's in Montreal have repeated Dr. Taylor's results with less sensitive measurement techniques for myocardial performance.

  2. Autologous bone marrow derived stromal cells as source of mesenchymal stem cells .

    The advantage of this technique is that stromal cells seem to have primitive stem cell like qualities for differentiation and are easily harvested with a simple bone marrow biopsy in the hip of the patient. Techniques for harvesting bone marrow are well established and routine practice in all hospitals. This method also features lack of immune response. There are no ethical issues associated with this method.

    Research Partners: Dr. Ray Chiu's laboratory at McGill University of Montreal. Dr. Chiu is also Editor-in-Chief of the Journal of Cardiac and Vascular Regeneration: Angiogenesis and Myogenesis, from Basic to Therapeutic. Bioheart has an agreement to acquire exclusive rights to all heart muscle regeneration and angiogenesis technologies developed by this laboratory and has entered into a forward research collaboration to bring this method to clinical application.

    1. The bone marrow stroma micro-environment is a complex network of cells and extracellular matrix.

    2. Bone marrow stroma cells have a definite role in the "mesengenic process" for self repair as described by Al Caplan in Clinics Plast Surg 1994;21:429-435.

    3. This promotes a method of regeneration from residual cycling stem cells.

    4. It is clear that bone marrow also contains cells that meet criteria for stem cells of non-hematopoietic tissue, and they are currently referred to as mesenchymal stem cells, because of their ability to differentiate into cells. These cells are found in the supporting structures found in bone marrows.

    5. Makino et al. demonstrated in J Clin Invest 1999;103:697-705 that cardiomyocytes can be generated from marrow stromal cells in vitro.

    6. Dr. Ray Chiu's group at McGill University was the first to demonstrate differentiation from stromal cells to cardiomyocytes in vivo. Dr. Chiu's lab has numerous related patents pending.

  3. Embyronic stem cells derived from culturing with patient's own genetic material.

    This technique is expected to produce the most vibrant and proliferative transplantation cells. Certain studies have demonstrated the survival of embryonic or fetal transplanted cells while adult autologous cells have not been successfully grafted to host muscle. By utilizing the method of introducing a patient's own genetic material into a donated egg with chromosomes removed, it is expected that immune response to the transplanted cells will be minimized.

    Research Partners: Stem Cell Labs, Inc., Palo Alto, California, a newly formed commercial laboratory. Bioheart is currently in discussions with various scientists worldwide to develop a university based research initiative in this area. Bioheart is negotiating with certain inventors to obtain related patents at the time of this publication.

    1. Genetic material of patient is injected into donated egg with chromosome removed. These altered eggs are grown for a week in a laboratory, where they develop into early stage embryos or cultured blastocysts. Outer covering is removed and inner cell mass is cultured with additive chemical which disaggregates cells into clumps. Colonies of embryonic stem cells are grown. A differentiation factor is added to form cardiomyocytes (heart muscle cells) which are encoded with the patient's own DNA to avoid rejection after transplantation into that patient's damaged heart.

    2. Klug et al transfected into embryonic stem cells and proved the isolation of embryonic stem cells.



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Bioheart, Inc.
Cardiovascular Healthcare
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