Howard Leonhardt to Present 25 Years of Experience Muscle Stem Cell Transplantation @ Los Angeles Cardiology Conference
What we have learned and where do we go from here?
The Beverly Hills Hotel
- Embyronic stem cells do not work in myocardial scar tissue. They form fibroblasts or more scar. They die out.
- Cardiomyocytes die out when injected in myocardial scar tissue (they require too much oxygen and nutrients) and cannot be multiplied to therapeutic dosages. They are electrically unstable in scar tissue.
- Adipose, blood, bone marrow, placenta and embryonic stem cells cannot grow new muscle in scar tissue.
- Cardiac stem cells only work to form new muscle on the rim edge of a scar, not in the center.
- Only myoblasts or immature myoblasts have demonstrated an ability to form new contractile muscle in deep scar tissue in advanced heart failure patients.
- Over 4,000 animal studies have been completed for muscle stem cell repair of damaged heart tissue since Dr. Race Kao’s and Dr. George Magovern’s original work in 1988 which was published in The PHYSIOLOGIST in 1989, with the nearly universal majority yielding positive results for myoblast transplantation.
- More than 400 patients have been enrolled in clinical trials for myoblast transplantation since June of 2000.
- Direct needle catheter injection into scar tissue is far superior to coronary infusion or other methods.
- Targeted cell delivery is not needed. The cells naturally spread all over scar tissue if they are injected anywhere near the scar tissue and migrate to the injured tissue areas.
- In clinical trials, 84% of myoblast-treated heart-failure patients have improved; only 16% worsened.
- 69% of non-treated control or placebo patients in clinical trials have worsened.
- 33% of myoblast-treated patients with only one injection session exhibited substantial improvement in cardiac function and/or quality of life or exercise capacity improving up to two full heart failure classes.
- Myoblast-treated patients in Phase II/III controlled studies (randomized, double blinded, placebo controlled) improved 95.7 meters over placebo patients (-4 meters decline) in exercise capacity in clinical trials. No other stem cell type, drug or device has ever beat 53 meters improvement in a controlled trial; cardiac resynchronization therapy (CRT) pacers achieved an improvement of 20 meters, cardiac stem cells increased exercise capacity by 53 meters, allogeneic bone marrow cells 10 meters, while CHF drugs were associated with a 4-meter decline.
- It is expected based on data available to date that repeat myoblast transplantation will reduce by half hospitalizations from heart failure. Heart-failure hospitalizations and associated care are the single leading drain on Medicare in the USA. The leading cause of hospitalization in the USA for people over 60.
- Myoblast-transplanted patients have a lower incidence of arrhythmias six months and one year after treatment than non-treated patients. Premature ventricular contraction (PVC) data demonstrates 0.05% for myoblast-treated patients and close to 3% for non-treated patients.
- 33% of myoblast-treated patients improve two heart failure classes.
- 33% of myoblast-treated patients have greater than 15% improvement in left ventricular ejection fraction (LVEF) via dobutamine stress echo studies.
- Pressure-volume (PV) loop studies have demonstrated myoblast-treated patients have substantial positive reverse re-modeling.
- Close to $300 million has been spent to date on myoblast transplantation for heart failure research since 1988. Bioheart, Inc. has invested over $100 million to advancing this development.
- Pre-treating scar with microRNAs, stromal cell-derived factor-1 (SDF-1) and nutrient hydrogel before cell transplantation can improve results.
- Genetically modifying cells to over-express SDF-1 can double improvement results and the consistency of results. Myoblasts alone lead to 27% improvement, while SDF-1 myoblasts result in 54% improvement. 66% of test subjects received substantial new muscle formation with SDF-1 myoblasts compared to 33% with ordinary myoblasts.
- New muscle formed with myoblasts is stretch-activated.
- Injecting cardiac stem cells or induced pluripotent stem (iPS) cells at the rim edge of scar and myoblasts in the center of scar in combination may be worth studying.
- Electrical stimulation before, during and after stem-cell transplantation can dramatically improve results.
- Nutrient hydrogel can help improve myoblast cell engraftment in scar tissue.
- Repeat injection sessions can dramatically improve results – Bioheart sponsored study F. Prosper et. al. was published in the European Heart Journal – another similar confirming pre-clinical study was published in Japan.
- Stem cell pumps are being developed to deliver cells and growth factors over time.
- Wireless energy devices for directing stem cell therapies non-invasively are being developed.
- For more information on the 13th Annual Controversies and Advances in the Treatment of Cardiovascular Disease visit – http://promedicacme.com/meeting/Controversies-and-Advances-in-the-96.html To learn more about advances in regenerative medicine, visit http://www.bioheartinc.com, www.calxstars.com ;and http://www.leonhardtventures.com.
Bioheart is focused on completing its Phase II/III MIRROR study for MyoCell in treating advanced heart failure. The product candidate has been in clinical trials since May 2001. The company believes, after 10 years of clinical trials that followed pre-clinical studies dating to 1988, that it may be on the final leg toward qualifying to apply for a biologics license-approval FDA panel review. Approximately 130 more patients are needed in the randomized, double-blinded, placebo-controlled MARVEL Phase II/III Part II study. MyoCell is a clinical muscle-derived stem cell therapy designed to populate regions of scar tissue within a patient’s heart with new living cells for the intended purpose of improving cardiac function and quality of life in chronic heart failure patients.