Using Sleeping Stem Cells to Treat Aggressive Leukemias


British scientists have discovered that aggressive forms of leukemia (blood cancers) do not displace normal stem cells from the bone marrow, but instead, put them to sleep. If the normal stem cells are asleep, it implies that they can be awakened. This offers a new treatment strategy for acute myeloid leukemia or AML.

This work comes from researchers at Queen Mary, University of London with the support of Cancer Research UK’s London Research Institute.

In the United Kingdom, approximately 2,500 people are diagnosed with AML each year. The disease strikes young and old patients and the majority of patients die from AML.

In healthy patients, the bone marrow contains hematopoietic stem cells (HSCs) that divide to form either a common myeloid precursor (CMP) or a common lymphoid precursor (CLP) that differentiate into various kinds of white blood cells or red blood cells or lymphocytes. Individuals afflicted with AML, however, have bone marrow invaded by leukemic myeloid blood cells. Since red blood cells are derived from the myeloid lineage, AML causes red blood cell deficiencies (anemia), and the patient becomes tired, and is at risk for excessive bleeding. AML patients are also more vulnerable to infection those white blood cells that fight infections are not properly formed.

HSC differentiation2

David Taussig from the Barts Center Institute at Queen Mary, University of London said that the widely accepted explanation for these symptoms is that the cancerous stem cells displace or destroy the normal HSCs.

However, Taussig and his colleagues have found in bone marrow samples from mice and humans with AML contain plenty of normal HSCs. Thus, AML is not destroying or displacing the HSCs. Instead, the cancerous stem cells appear to be turning them off so that they cannot form HSCs. If Taussig and his coworkers and collaborators had determine how these leukemic myeloid blood cells are shutting off the normal HSCs, they might be able to design treatments to turn them back on.

Such a treatment strategy would increase the survival of AML patients. Only 40% of younger patients are cured of AML, and the cure rate for older patients in much lower. Current treatments that include chemotherapy and bone marrow transplants are not terribly successful with older patients.

Taussig’s group examined the levels of HSCs in the bone marrow of mice that had been transplanted with human leukemic myeloid cells from AML patients. They discovered that the numbers of HSCs stayed the same, but these same HSCs failed to transition through the developmental stages that result in the formation of new blood cells. When Taussig and his group examined bone marrow from 16 human AML patients, they discovered a very similar result.

Even though AML treatment has come a long way in the last ten years, there is still an urgent need for more effective treatments to improve long-term survival. This present study greatly advances our understanding of what’s going on in the bone marrow of AML patients. The future challenge is to turn this knowledge into treatments.

Under normal circumstances, stress on the body will boost HSC activity. For example, when the patient hemorrhages, the HSCs kick into action to produce more red blood cells that were lost during the bleed. However, the cancer cells in the bone marrow are somehow over-riding this compensatory mechanism and the next phase of this research will determine exactly how they do it.

BrainStorm Announces that There Are No Dangerous Side Effects Observed in NurOwn Trial


A developer of innovative stem cell technologies, BrainStorm Cell Therapeutics Inc. has developed a stem cell treatment called NurOwn for central nervous system-based disorders. NurOwn™ is a product derived from human bone marrow mesenchymal stem cells. After these cells are collected from a patient by means of a bone marrow aspiration (which not nearly as invasive as a bone marrow biopsy), they are differentiated into nerve-like cells that can release the neurotransmitter dopamine and a nervous system-specific growth factor called glial-derived neurotrophic factor (GDNF). Dopamine cell damage and death is the hallmark of Parkinson’s Disease (PD), and GDNF-producing cells can protect healthy dopamine-producing cells and repair degenerated cells. This halts the progression of PD and other neurodegenerative diseases. BrainStorm’s NurOwn™ therapy for PD replaces degenerated dopamine-producing nerve cells and strengthens them with GDNF.

BrainStorm has just announced patient data from its ALS combined phase I & II human clinical trial. ALS patients who were treated with NurOwn, a stem cell-based product that BrainStorm had developed, did not show any significant side effects to the NurOwn treatment. Therefore, so far, NurOwn seems to be safe.

The leader of this clinical trial at Hadassah Medical Center, Prof. Dimitrios Karussis, stated, “There have been no significant side effects in the initial patients we have treated with BrainStorm’s NurOwn technology. In addition, even though we are conducting a safety trial, the early clinical follow-up of the patients treated with the stem cells shows indications of beneficial clinical effects, such as an improvement in breathing and swallowing ability as well as in muscular power. I am very excited about the safety results, as well as these indications of efficacy, we are seeing. This may represent the biggest hope in this field of degenerative diseases, like ALS.”

The Hadassah Medical Center ethics committee reviewed the safety data from the first four patients who were implanted with NurOwnTM, and concluded that the clinical trial should proceed with implanting the next group of ALS patients.

BrainStorm’s President, Chaim Lebovits, remarked: “We are happy to report that the first patients treated with our NurOwn technology did not present any significant side effects. This supports and strengthens our belief and trust in our technology. Based on the interim safety report, the hospital ethical and safety committee granted the company approval to proceed with treating the next patients. We are pleased with the progress we are making and look forward to continuing to demonstrate the safety of NurOwn in the future.”

This study is headed by Prof. Karussis, MD, PhD, head of Hadassah’s Multiple Sclerosis Center and a member of the International Steering Committees for Bone Marrow and Mesenchymal Stem Cells Transplantation in Multiple Sclerosis (MS), and a scientific team from BrainStorm headed by Prof. Eldad Melamed. This clinical trial is being conducted at Hadassah Medical Center in Israel in collaboration with BrainStorm and utilizes BrainStorm’s NurOwn technology for growing and modifying autologous adult human stem cells to treat ALS, which is often referred to as Lou Gehrig’s Disease. The initial phase of the study is designed to establish the safety of NurOwn, but will also be expanded later to assess efficacy of the treatment.