HIV Positive Men Show No Signs of HIV after Bone Marrow Transplant and Discontinuation of Anti-Retroviral Therapy

Source: Brigham and Women's Hospital

Date: July 3, 2013

Summary:

Boston, MA - Two Brigham and Women's Hospital patients with longstanding HIV infections who underwent bone marrow transplants have stopped anti-retroviral therapy and have no detectable HIV in their blood cells.  One patient stopped anti-retroviral therapy 15 weeks ago, the other stopped 7 weeks ago.  These new findings will be presented on July 3, 2013 at the International AIDS Society Conference (IAS 2013) in Kuala Lumpur, Malaysia by Timothy Henrich, MD and Daniel Kuritzkes, MD, physician-researchers in the Division of Infectious Diseases at Brigham and Women's Hospital.

Stem Cell Researchers Use Gene Therapy to Restore Immune Systems in 'Bubble Boy' Disease

Source: University of California, Los Angeles (UCLA), Health Sciences
Date: September 11, 2012

Summary:

UCLA stem cell researchers have found that a gene therapy regimen can safely restore immune systems to children with so-called "Bubble Boy" disease, a life threatening condition that if left untreated can be fatal within one to two years.

In the 11-year study, researchers were able to test two therapy regimens for 10 children with ADA-deficient severe combined immunodeficiency (SCID). During the study, they refined their approach to include a light dose of chemotherapy to help remove many of the blood stem cells in the bone marrow that are not creating an enzyme called adenosine deaminase (ADA), which is critical for the production and survival of healthy white blood cells, said study senior Dr. Donald Kohn, a professor of pediatrics and of microbiology, immunology, and molecular genetics in Life Sciences and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA.

The refined gene therapy and chemotherapy regimen proved superior to the other method tested in the study, restoring immune function to three of the six children who received it, Kohn said. Going forward, an even further refined regimen using a different type of virus delivery system will be studied in the next phase of the study, which already has enrolled eight of the 10 patients needed.

The study appears Aug. 30 in the advance online issue of the peer-reviewed journal Blood.

New Genetic Mechanism for Controlling Blood Cell Development and Blood Vessel Integrity Found

Source: University of Wisconsin-Madison
Date: September 10, 2012

Summary:

The protein GATA2 is known as a "master regulator" of blood cell development. When a mutation occurs in the gene that makes GATA2, serious blood diseases such as acute myeloid leukemia can result. Zooming in on the GATA2 gene, University of Wisconsin-Madison researchers and their collaborators at the National Institutes of Health (NIH) have discovered unexpectedly that a small DNA sequence drives this powerful master regulator. The sequence plays an essential role in controlling GATA2 production and generating self-renewing blood stem cells responsible for the earliest steps in the development of blood cells of all kinds — red cells to transport oxygen and white cells to fight infection.

The researchers also found that the DNA sequence, which they call the +9.5 GATA2 switch site, ensures that blood vessels function properly to prevent hemorrhaging. Until now, GATA2 had not been implicated in blood vessel integrity. The study appears in The Journal of Clinical Investigation (online Sept. 10, 2012).

Scientists Discover 'Missing Link' Between Stem Cells and the Immune System

Source: University of California, Los Angeles (UCLA), Health Sciences
Date: September 2, 2012

Summary:

UCLA researchers have discovered a type of cell that is the "missing link" between bone marrow stem cells and all the cells of the human immune system, a finding that will lead to a greater understanding of how a healthy immune system is produced and how disease can lead to poor immune function. The studies were done using human bone marrow, which contains all the stem cells that produce blood during postnatal life.

Understanding the process of normal blood formation in human adults is a crucial step in shedding light on what goes wrong during the process that results in leukemias, or cancers of the blood. The study appears Sept. 2 in the early online edition of Nature Immunology.

Scientists Discover Key Pathway For Development of Insulin-producing Cells

Source: Stanford University School of Medicine
Date: July 16, 2012

Summary:

Researchers at the Stanford University School of Medicine have identified a molecular signaling pathway that drives the growth and maturation of young human beta cells — the insulin-producing cell type in the pancreas that malfunctions in diabetes — in mice and humans. The pathway, called the Cn/NFAT pathway, has been shown to be important in the growth and development of many cell types, including immune cells and neurons. But this is the first time it’s been shown to be involved in the development of human beta cells. The research is published July 17 in Developmental Cell.

Researchers Block Pathway to Cancer Cell Replication NOTCH1 Signaling Promotes T-Cell Acute Lymphoblastic Leukemia-Initiating Cell Regeneration

Source: University of California - San Diego
Date: July 2, 2012

Summary:

Research suggests that patients with leukemia sometimes relapse because standard chemotherapy fails to kill the self-renewing leukemia initiating cells, often referred to as cancer stem cells. In such cancers, the cells lie dormant for a time, only to later begin cloning, resulting in a return and metastasis of the disease.

One such type of cancer is called pediatric T cell acute lymphoblastic leukemia, or T-ALL, often found in children, who have few treatment options beyond chemotherapy. A team of researchers at the University of California, San Diego School of Medicine studied these cells in mouse models that had been transplanted with human leukemia cells. They discovered that the leukemia initiating cells which clone, or replicate, themselves most robustly activate the NOTCH1 pathway, usually in the context of a mutation.

Earlier studies showed that as many as half of patients with T-ALL have mutations in the NOTCH1 pathway – an evolutionarily conserved developmental pathway used during differentiation of many cell and tissue types. The new study shows that when NOTCH1 activation was inhibited in animal models using a monoclonal antibody, the leukemia initiating cells did not survive. In addition, the antibody treatment significantly reduced a subset of these cancer stem cells (identified by the presence of specific markers, CD2 and CD7, on the cell surface).

The study results suggest that such therapy would also be effective in other types of cancer stem cells, such as those that cause breast cancer, that also rely on NOTCH1 for self-renewal.

Mechanism That Maintains Stem Cells Readiness Identified

Source: University of Texas Southwestern Medical Center
Date: May 31, 2012

Summary:

An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow, researchers at University of Texas Southwestern Medical Center report today in the journal Nature.

The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies, Dr. Zhang said, showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a car’s brakes.

In the case of stem cells, inhibition keeps them in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they don’t use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells’ other major activity, Dr. Zhang said. He stressed that the inhibition doesn’t cause them to create new stem cells but does preserve their potential to do so.

In future research, the scientists hope to find subtle differences between stem cells and leukemia cells that will identify treatments to block the receptors’ action only in leukemia.

New York Stem Cell Foundation Scientist Grows Bone From Human Embryonic Stem Cells

Source: New York Stem Cell Foundation
Date: May 14, 2012

Summary:
 
NEW YORK, NY -- Dr. Darja Marolt, an Investigator at The New York Stem Cell Foundation (NYSCF) Laboratory, is lead author on a study showing that human embryonic stem cells can be used to grow bone tissue grafts for use in research and potential therapeutic application. Dr. Marolt conducted this research as a post-doctoral NYSCF – Druckenmiller Fellow at Columbia University in the laboratory of Dr. Gordana Vunjak- Novakovic.

The study, published in the early online edition of Proceedings of the National Academy of Sciences during the week of May 14th, is the first example of using bone cell progenitors derived from human embryonic stem cells to grow compact bone tissue in quantities large enough to repair centimeter-sized defects. When implanted in mice and studied over time, the implanted bone tissue supported blood vessel ingrowth, and continued development of normal bone structure, without demonstrating any incidence of tumor growth.

Genetically Modified T Cell Therapy Shown to be Safe, Lasting in Decade-Long Penn Medicine Study of HIV Patients

Source: University of Pennsylvania School of Medicine
Date: May 2, 2012

Summary:

HIV patients treated with genetically modified T cells remain healthy up to 11 years after initial therapy, researchers from the Perelman School of Medicine at the University of Pennsylvania report in the new issue of Science Translational Medicine. The results provide a framework for the use of this type of gene therapy as a powerful weapon in the treatment of HIV, cancer, and a wide variety of other diseases.

STUDY USING STEM CELL THERAPY SHOWS PROMISE IN FIGHT AGAINST HIV

Source: University of California - Davis Health System
Date: May 1, 2012

Summary:

(SACRAMENTO, Calif. — UC Davis Health System researchers are a step closer to launching human clinical trials involving the use of an innovative stem cell therapy to fight the virus that causes AIDS. In a paper published in the May issue of the Journal of Virology, the UC Davis HIV team demonstrated both the safety and efficacy of transplanting anti-HIV stem cells into mice that represent models of infected patients. The technique, which involves replacing the immune system with stem cells engineered with a triple combination of HIV-resistant genes, proved capable of replicating a normally functioning human immune system by protecting and expanding HIV-resistant immune cells. The cells thrived and self-renewed even when challenged with an HIV viral load.

How Stem Cell Therapy Can Keep the Immune System Under Control

Source: University of Southern California
Date: April 26, 2012

Summary:

A new study, appearing in Cell Stem Cell and led by researchers at the University of Southern California, outlines the specifics of how autoimmune disorders can be controlled by infusions of mesenchymal stem cells (MSC). Highly versatile MSC originate from the mesoderm, or middle layer of tissue, in a developing embryo. MSC can be isolated from several kinds of human tissue, including bone marrow and the umbilical cord.

Engineered Stem Cells Seek out and Kill HIV in Living Mice

Source: University of California, Los Angeles (UCLA), Health Sciences
Date: April 12, 2012

Summary:

Expanding on previous research providing proof-of-principal that human stem cells can be genetically engineered into HIV-fighting cells, a team of UCLA researchers have now demonstrated that these cells can actually attack HIV-infected cells in a living organism.

The study, published April 12 in the journal PLoS Pathogens, demonstrates for the first time that engineering stem cells to form immune cells that target HIV is effective in suppressing the virus in living tissues in an animal model, said lead investigator Scott G. Kitchen, an assistant professor of medicine in the division of hematology and oncology at the David Geffen School of Medicine at UCLA and a member of the UCLA AIDS Institute.

Determining a Stem Cell's Fate: Biologists Scour Mouse Genome for Genes and Markers That Lead to T Cells

Source: California Institute of Technology
Date: April 12, 2012

Summary:

In studies that mark a major step forward in the understanding of stem cells' fates, a team of researchers from the California Institute of Technology (Caltech) has traced the stepwise developmental process that ensures certain stem cells will become T cells -- cells of the immune system that help destroy invading pathogens. The group's findings appear in the April 13 issue of the journal Cell.

The researchers studied multipotent hematopoietic precursor cells -- stem-cell-like cells that express a wide variety of genes and have the capability to differentiate into a number of different blood-cell types, including those of the immune system. Taking into consideration the entire mouse genome, the researchers pinpointed all the genes that play a role in transforming such precursor cells into committed T cells and identified when in the developmental process they each turn on. At the same time, the researchers tracked genes that could guide the precursor cells to various alternative pathways. The results showed not only when but also how the T-cell-development process turned off the genes promoting alternative fates.

New Method Yields Insulin-Producing Pancreatic Cell Clusters

Source: Mary Ann Liebert, Inc., Publishers
Date: 04 April 2012

Summary:

Three-dimensional clusters of pancreatic beta-cells that live much longer and secrete more insulin than single cells grown in the laboratory are valuable new tools for studying pancreatic diseases such as diabetes and for testing novel therapies. This cutting-edge advance is described in an article in Tissue Engineering, Part C, Methods.

Cancer Stem Cell Vaccine in Development Shows Antitumor Effect

Source: American Association for Cancer Research
Date: April 2, 2012

Summary:

PHILADELPHIA — Scientists may have discovered a new paradigm for immunotherapy against cancer by priming antibodies and T cells with cancer stem cells, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.

In the study, the researchers extracted cancer stem cells from two immunocompetent mouse models and used them to prepare the vaccine. They discovered that the enriched cancer stem cells were immunogenic and much for effective more effective as an antigen source compared with the unselected tumor cells normally used in previous immunotherapy trials. The researchers also found that cytotoxic T lymphocytes harvested from cancer stem cell-vaccinated hosts were capable of killing cancer stem cells in vitro.

Single antibody shrinks variety of human tumors transplanted into mice, study shows

Source: Stanford University School of Medicine
Date: March 26, 2012

Summary:

Human tumors transplanted into laboratory mice disappeared or shrank when scientists treated the animals with a single antibody, according to a new study from the Stanford University School of Medicine. The antibody works by masking a protein flag on cancer cells that protects them from macrophages and other cells in the immune system. The scientists achieved the findings with human breast, ovarian, colon, bladder, brain, liver and prostate cancer samples.

It is the first antibody treatment shown to be broadly effective against a variety of human solid tumors, and the dramatic response — including some overt cures in the laboratory animals — has the investigators eager to begin phase-1 and –2 human clinical trials within the next two years. The antibody treatment also significantly inhibited the ability of the tumors to metastasize throughout the animals’ bodies. The research was published online March 26 in the Proceedings of the National Academy of Sciences.

New transplant method may let kidney recipients live life free of anti-rejection medication

Source: University of Louisville / Northwestern Medicine
Date: March 7, 2012

Summary:

New ongoing research published March 7 in the journal Science Translational Medicine suggests organ transplant recipients may not require anti-rejection medication in the future thanks to the power of stem cells, which may prove to be able to be manipulated in mismatched kidney donor and recipient pairs to allow for successful transplantation without immunosuppressive drugs. Northwestern Medicine® and University of Louisville researchers are partnering on a clinical trial to study the use of donor stem cell infusions that have been specially engineered to “trick” the recipients’ immune system into thinking the donated organ is part of the patient’s natural self, thus gradually eliminating or reducing the need for anti-rejection medication.

Reuters published a news story on this finding today.

Stem Cell Therapy Reverses Diabetes: Stem Cells from Cord Blood Used to Re-Educate Diabetic's Own T Cells

Source: BioMed Central
Date: January 9, 2012

Summary:

Type 1 diabetes is caused by the body's own immune system attacking its pancreatic islet beta cells and requires daily injections of insulin to regulate the patient's blood glucose levels. A new method described in BioMed Central's open access journal BMC Medicine uses stem cells from cord blood to re-educate a diabetic's own T cells and consequently restart pancreatic function reducing the need for insulin.

HIV Drug Reduces Graft-versus-Host Disease in Stem Cell Transplant Patients, Penn Study Shows

Source: University of Pennsylvania School of Medicine
Date: December 13, 2011

Summary:

(SAN DIEGO) -- An HIV drug that redirects immune cell traffic appears to significantly reduce the dangerous complication graft-versus-host disease (GvHD) in blood cancer patients following allogeneic stem cell transplantation (ASCT), according to new research from the Perelman School of Medicine at the University of Pennsylvania that will be presented today at the 53rd American Society of Hematology Annual Meeting. Standard GvHD treatments suppress the immune system, reducing – but not eliminating – the risk of developing the common problem. In the current trial, treatment with the HIV drug maraviroc dramatically reduced the incidence of GvHD in organs where it is most dangerous -- without compromising the immune system and leaving patients more vulnerable to severe infections.

Scientists Engineer Blood Stem Cells to Fight Melanoma

Source: University of California - Los Angeles
Date: November 28, 2011

Summary:

Researchers from UCLA's cancer and stem cell centers have demonstrated for the first time that blood stem cells can be engineered to create cancer-killing T-cells that seek out and attack a human melanoma. The researchers believe this approach could be useful in 40 percent of Caucasians with this malignancy.

Done in mouse models, the study serves as first proof-of-principle that blood stem cells, which make every cell type found in blood, can be genetically altered in a living organism to create an army of melanoma-fighting T-cells, said Jerome Zack, study senior author and a scientist with UCLA's Jonsson Comprehensive Cancer Center and the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. The study appears Nov. 28, 2011 in the early online edition of the peer-reviewed journal Proceedings of the National Academy of Sciences.