Science in Society Archive

Important Books & Reports

Banishing Glyphosate

Banishing Glyphosate - Dr. Eva Sirinathsinghji, Dr. Mae-Wan Ho and others

Glyphosate/Roundup, falsely claimed by Monsanto to be safe and harmless, has become the world’s most widely and pervasively used herbicide; it has brought rising tides of birth defects, cancers, fatal kidney disease, sterility, and dozens of other illnesses - more

Ban GMOs Now

Ban GMOs Now - Dr. Mae-Wan Ho and Dr. Eva Sirinathsinghji

Health & environmental hazards especially in the light of the new genetics - more

Living Rainbow H2O

Living Rainbow H2O - Dr. Mae-Wan Ho

A unique synthesis of the latest findings in the quantum physics and chemistry of water that tells you why water is the “means, medium, and message of life” - more

The Rainbow and the Worm - the Physics of Organisms

The Rainbow and the Worm - the Physics of Organisms - Dr. Mae-Wan Ho

“Probably the Most Important Book for the Coming Scientific Revolution” - more

Patient’s Own Stem Cells Mend Heart

Adult stem cells proving themselves in the clinic. Dr. Mae-Wan Ho reports

From lab to clinic

Over the past three years, adult stem cell research has been moving from the lab to the clinic with a string of promising outcomes in treating conditions such as chronic arthritis, severe systemic lupus erythematosus, Crohn’s disease, cancer, and repairing damaged heart after heart attack (see "Hushing up adult stem cells", SiS 13/14; "Human cloning & the stem cell debate", SiS 16).

Follow-up research in several laboratories have now confirmed that stem cells in the bone marrow or circulating in the bloodstream are indeed both safe and effective in heart repair, helping to recover the heart’s ability to contract properly to deliver oxygen and nutrients to the rest of the body.

Non-surgical treatment with patient’s own cells

After a heart attack, the muscle cells at the periphery of the damaged area tend to overgrow in order to make up for the dead or damaged cells. But this initiates a further loss of muscle cells, causing the damaged area to expand and to be replaced by useless scar tissue, eventually ending in heart failure. Many drugs are aimed at preventing this process of ‘cardiac remodelling’ after a heart attack, so as to stop the heart muscle cells from overgrowth and dying.

Researchers at Heinrich-Heine-University of Dusseldorf in Germany, who reported the first success in repairing a patient’s damaged heart three years ago, have since treated ten more patients, all male, by transplanting the patients’ own bone marrow cells (BMCs) [1]. The BMCs, collected the day before, purified and expanded in culture overnight, were introduced into the blocked (infarct) artery that precipitated the heart attack during balloon dilatation of the artery that’s part of the standard treatment. Another 10 male patients, who refused the cell therapy, were treated with the standard therapy only.

After 3 months follow-up, the damaged region was found to have decreased significantly in the group receiving BMC therapy, from 30+13 to 12+7%, and significantly smaller than the standard therapy group. Similarly, the damaged wall movement velocity increased significantly only in the cell therapy group, from 2.0+1.1 to 4.0+2.6cm/s. There were also significant improvements in the cell therapy group that reflected the heart’s ability to contract properly and deliver blood to the body.

The regeneration of healthy muscle tissue in the damaged area was accompanied by the formation of new blood vessels. An important contribution to the success of the treatment, the researchers pointed out, was the use of a non-surgical procedure thus avoiding risks associated with surgical operations. The introduction of cells through the infarct artery also ensured that cells would be transported to areas requiring tissue regeneration.

Stem cells from blood just as effective

In a further study, the same researchers compared the effect of BMCs with progenitor cells purified directly from the blood [2]. In this protocol, 20 patients were randomly assigned to receive either of the treatments twenty-four hours after heart attack.

Patients receiving BMCs had their bone marrow aspirated on the morning of the day of cell transplant, and the cells were used directly after purification without expansion in culture. Those receiving blood progenitor cells had 250ml of blood collected immediately after random assignment. Mononuclear cells were purified and cultured for 3 days before being re-infused into the infarct artery.

Both treatment groups improved significantly in the measured parameters of heart function after 4 months; there were no difference between the two groups in the extent of improvement.

In contrast, the control group (of 11) who did not receive cell therapy showed no significant improvement in any of the same parameter at 4 months.

A randomised trial

Another research team at Hannover Medical School in Germany carried out a randomised trial on the BMC therapy [3]. Here, 60 patients were randomly assigned in equal numbers to either a control group that received optimum post-infarct medical treatment, or BMC (direct, no expansion in vitro) transplant at about 5 days after similar coronary intervention. The endpoint measurement was the change in global left ventricle ejection fraction (LVEF) from baseline to 6 months’ follow-up, as determined by cardiac MRI (magnetic resonance imaging).

Global LVEF at baseline, determined at about three and a half days after post-infarct medical treatment was 51.3 +9.3% in controls and 50.0 +10.0% in the BMC group. After 6 months, however, mean global LVEF had increased only 0.7% in controls compared to 6.7% in the cell group.

The researchers concluded: "The effects of cell transfer were over and above benefits associated with established strategies to promote functional recovery after acute myocardial infarction", which included both physical and pharmacological interventions.

Mechanisms debated

Other researchers have cast doubt on whether the ability of bone marrow cells to mend damaged heart depends on the stem cells found in the bone marrow developing into heart muscle cells or capillaries (fine blood vessels) or both [4]; but that does not detract from the positive results obtained in the trials.

Researchers at Columbia University, New York, recently isolated from adult human bone marrow, endothelial progenitor cells or angioblasts that migrate to ischemic (blood-flow deprived) myocardium (muscle wall of the heart), where they induce new blood vessel formation and prevent myocardial remodelling.

They have now shown in experiments on rats [5] that increasing the number of human angioblasts to the infarct area induced a dose-dependent new blood vessel formation with development of progressively larger-sized capillaries. This results in sustained improvement in cardiac function by protecting against cell death, and inducing proliferation and regeneration of the rat heart muscle cells.

The researchers suggest that in the cardiac remodelling process after heart attack, those heart muscle cells that overgrow to compensate for the dead cells eventually die because the capillary network cannot provide the increase in blood flow necessary for the cells to survive.

Thus, agents (possibly chemical) that increase bone marrow angioblasts homing in on the heart muscle to form new blood vessels could effectively induce endogenous heart-muscle cells to enter the cell cycle and help the heart regenerate and recover.

Article first published 13/01/05



References

  1. Strauer Bodo E, Brehm M, Zeus T, Köstering M, Hernandez A, Sorg RV, Kögler G and Wernet P. Repair of infracted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002, 106, 1913-8.
  2. Assmus B, Schächinger V, Teupe C, et al. Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 2002, 106, 3009-17.
  3. Wollert KaiC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 2004, 364, 141-8.
  4. Wagers AJ and Weissman IL. Plasticity of adult stem cells. Cell 2004, 116, 636-48.
  5. Schuster MD, Kocher AA, Seki T, Martens TP, Xiang G, Homma S, and Itescu S. Myocardial neovascularization by bone marrow angioblasts results in cardiomyocyte regeneration. Am J Physiol Heart Circ Physiol 2004, 287, H525-H532

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