Navigation Links
Reprogramming patients' cells offers powerful new tool for studying, treating blood diseases
Date:7/30/2013

First produced only in the past decade, human induced pluripotent stem cells (iPSCs) are capable of developing into many or even all human cell types. In new research, scientists reprogrammed skin cells from patients with rare blood disorders into iPSCs, highlighting the great promise of these cells in advancing understanding of those challenging diseasesand eventually in treating them.

"The technology for generating these cells has been moving very quickly," said hematologist Mitchell J. Weiss, M.D., Ph.D., corresponding author of two recent studies led by The Children's Hospital of Philadelphia (CHOP). "These investigations can allow us to better understand at a molecular level how blood cells go wrong in individual patientsand to test and generate innovative treatments for the patients' diseases."

Weiss, with Monica Bessler, M.D., Philip Mason, Ph.D., and Deborah L. French, Ph.D., all of CHOP, led a study on iPSCs and Diamond Blackfan anemia (DBA) published online June 6 in Blood. Another study by Weiss, French and colleagues in the same journal on April 25 focused on iPSCs in juvenile myelomonocytic leukemia (JMML).

In DBA, a mutation prevents a patient's bone marrow from producing normal quantities of red blood cells, resulting in severe, sometimes life-threatening anemia. This basic fact makes it difficult for researchers to discern the underlying mechanism of the disease: "It's very difficult to figure out what's wrong, because the bone marrow is nearly empty of these cells," said Bessler, the director of CHOP's Pediatric and Adult Comprehensive Bone Marrow Failure Center.

The study team removed fibroblasts (skin cells) from DBA patients, and in cell cultures, using proteins called transcription factors, reprogrammed the cells into iPSCs. As those iPSCs were stimulated to form blood tissues, like the patient's original mutated cells, they were deficient in producing red blood cells.

However, when the researchers corrected the genetic defect that causes DBA, the iPSCs developed into red blood cells in normal quantities. "This showed that in principle, it's possible to repair a patient's defective cells," said Weiss.

Weiss cautioned that this proof-of-principle finding is an early step, with many further studies to be done to verify if this approach will be safe and effective in clinical use.

However, he added, the patient-derived iPSCs are highly useful as a model cell system for investigating blood disorders. For instance, DBA is often puzzling, because two family members may have the same mutation, but only one may be affected by the disease. Because each set of iPSCs is specific to the individual from whom they are derived, researchers can compare the sets to identify molecular differences, such as a modifier gene active in one person but not the other.

Furthermore, the cells offer a renewable, long-lasting model system for testing drug candidates or gene modifications that may offer new treatments, personalized to individual patients.

The second study in Blood provides a concrete example of using iPSCs for drug testing, specifically for the often-aggressive childhood leukemia, JMML. First the study team generated iPSCs from two children with JMML, and then manipulated the iPSCs in cell cultures to produce myeloid cells that multiplied uncontrollably, much as the original JMML cells do.

They then tested the cells with two drugs, each able to inhibit a separate protein known to be highly active in JMML. One drug, an inhibitor of the MEK kinase, reduced the proliferation of cancerous cells in culture. "This provides a rationale for a potential targeted therapy for this specific subtype of JMML," said Weiss.

A stem cell core facility at CHOP, directed by study co-author Deborah French under the auspices of the hospital's Center for Cellular and Molecular Therapeutics, generated the iPSCs lines used in these studies. The facility's goal is to develop and maintain standardized iPSCs lines specific to a variety of rare inherited diseasesnot only DBA and JMML, but also dyskeratosis congenita, congenital dyserythropoietic anemia, thrombocytopenia absent radii (TAR), Glanzmann's thrombasthenia and Hermansky- Pudlak syndrome.

A longer-term goal, added Weiss, is for the iPSC lines to provide the raw materials for eventual cell therapies that could be applied to specific genetic disorders. "The more we learn about the molecular details of how these diseases develop, the closer we get to designing precisely targeted tools to benefit patients."


'/>"/>

Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

Related medicine news :

1. Reprogramming cells to fight diabetes
2. A relationship between cancer genes and the reprogramming gene SOX2 discovered
3. Doctors urged to talk to patients about parking cellphones
4. Inhalable gene therapy may help pulmonary arterial hypertension patients
5. Requiring some patients to get mental health treatment saves money
6. Looking at outcomes important to patients may improve results of cataract surgery
7. Diet Doc Medical Weight Loss Plans Now Encourages Natural Weight Loss With Fruits and Vegetables that Help Patients Lose Weight Fast and Live Longer
8. Itani Dental Explains How to Choose a Dentist for Special Needs Patients
9. Active Family Chiropractic of Gaithersburg, MD Introduces Nutra Disc, a New Dietary Supplement Designed to Support Patients’ Spinal Disc and Connective Tissue Health
10. Diet Doc Medical Weight Loss Plans Now Help Patients Eliminate Junk Food From Their Weight Loss Diets with Fat Burning Snack Ideas
11. PositiveSingles.com and The Henne Group Partner to Conduct a Study on HIV Patients in LA and DC in Hopes to Support the Creation of a Campaign in the Fight Against HIV
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... 2016 , ... "FCPX editors can now reveal their media with growing colorful ... Christina Austin - CEO of Pixel Film Studios. , ProSlice Color brings the ... can now reveal the media of their split screens with growing colorful panels. , ...
(Date:6/26/2016)... ... ... Quality metrics are proliferating in cancer care, and are derived from many ... the beholder, according to experts who offered insights and commentary in the current issue ... the full issue, click here . , For the American Society of Clinical ...
(Date:6/26/2016)... ... June 26, 2016 , ... Many women are confused ... endometriosis. These women need a treatment plan to not only alleviate symptoms and ... help for preservation of fertility and ultimately achieving a pregnancy. The specialists at ...
(Date:6/25/2016)... ... 25, 2016 , ... First Choice Emergency Room , the largest network ... the Medical Director of its new Mesquite-Samuell Farm facility. , “We are pleased ... location,” said Dr. James M. Muzzarelli, Executive Medical Director of First Choice Emergency Room. ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... A recent ... that most people are unfamiliar with. The article goes on to state that individuals ... also many of these less common operations such as calf and cheek reduction. The ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016 ... CAPR ), a biotechnology company focused on ... today announced that patient enrollment in its ongoing ... Duchenne) has exceeded 50% of its 24-patient target. ... in the third quarter of 2016, and to ...
(Date:6/23/2016)... , June 23, 2016 , ... on Thursday, July 7, 2016 , , , , LOCATION: ... , , , , EXPERT PANELISTS:  , , , ... Senior Industry Analyst, Christi Bird; Senior Industry Analyst, Divyaa Ravishankar and ... The global pharmaceutical industry is witnessing an exceptional era. ...
(Date:6/23/2016)... LONDON , June 23, 2016 ... environments  Oticon , industry leaders in ... the launch of Oticon Opn ™, the world,s ... world of possibilities for IoT devices.      ... Opn, Oticon introduces a number of ,world firsts,: ...
Breaking Medicine Technology: