Health,Stem Cells, and Technology

Sunday, May 27, 2012

SRM Mediated Recovery In Multiple Sclerosis

A molecule released from human mesenchymal stem cells that promotes growth appears to induce restoration of nerves and their function in rodent models of multiple sclerosis (MS), according to Dr. Robert H. Miller, Ph.D. and team at Case Western Reserve University School of Medicine. 


Mesenchymal stem cells (MSCs), a type of adult stem cell, have emerged as a potential therapy for a range of neural conditions. In animal models of multiple sclerosis, an autoimmune disease that targets parts of the brain tissue called oligodendrocytes and myelin, treatment with human MSCs results in functional improvement through two main pathways: 1. modulation of the immune response, and 2. myelin repair. The study demonstrated that SRM, sometime also referred to as conditioned medium, from human MSCs (MSC-CM) reduces functional deficits in mouse MOG35–55-induced experimental autoimmune encephalomyelitis (EAE) and promotes the development of oligodendrocytes and neurons. Functional assays identified hepatocyte growth factor (HGF) and its primary receptor cMet as critical in MSC-stimulated recovery in EAE, neural cell development, and remyelination. Active MSC-CM contained HGF, and exogenously supplied HGF promoted recovery in EAE, whereas cMet and antibodies to HGF blocked the functional recovery mediated by HGF and MSC-CM. Systemic treatment with HGF markedly accelerated remyelination in lysolecithin-induced rat dorsal spinal cord lesions and in slice cultures. These data strongly implicate HGF as one of the key mediators in MSC-stimulated functional recovery in animal models of multiple sclerosis. The data show that HGF is necessary for recovery, but do not show that HGF is sufficient for recovery; i.e. other SRM factors may be necessary for the recovery.





Ref: Nature Neuroscience
 
15,
 
862–870
 
(2012)

Friday, May 11, 2012

Extended Survival of Cancer Patients After Chemoprotective Stem Cell Therapy

Gene transfer of the P140K mutant of O6-methylguanine-DNA-methyltransferase (MGMT(P140K)) into autologous hematopoietic stem cells (HSC) removed from cancer patients provides a mechanism for drug resistance and the selective expansion of the blood cells.


Chemotherapy with alkylating agents used for treating malignant disease results in the decreased ability to produce blood cells (myelosuppression) that can significantly limit dose escalation of the chemotherapy and therefore often limit the clinical efficacy of the procedure. Previous studies (Milson and Williams, 2007, DNA Repair) have shown that gene therapy techniques using mutant methylguanine methyltransferase (P140K) gene–modified hematopoietic stem and progenitor cells may circumvent this problem by abrogating the toxic effects of chemotherapy on hematopoietic cells. The study by Dr. Hans-Peter Kiem and his colleagues at the University of Washington used this approach in the clinic with a small number of glioblastoma patients. The data show an efficient polyclonal engraftment of autologous P140K-modified hematopoietic stem and progenitor cells in three patients with glioblastoma. Increases in P140K-modified cells after transplant indicate selection of gene-modified hematopoietic repopulating cells. Longitudinal retroviral integration site (RIS) analysis identified more than 12,000 unique RISs in the three glioblastoma patients, with multiple clones present in the peripheral blood of each patient throughout multiple chemotherapy cycles. To assess safety, they monitored RIS distribution over the course of chemotherapy treatments. Two patients exhibited emergence of prominent clones harboring RISs associated with the intronic coding region of PRDM16 (PR domain–containing 16) or the 3′ untranslated region of HMGA2 (high-mobility group A2) genes with no adverse clinical outcomes. All three patients surpassed the median survival for glioblastoma patients with poor prognosis, with one patient alive and progression-free more than 2 years after diagnosis. Thus, transplanted P140K-expressing hematopoietic stem and progenitor cells are chemoprotective, potentially maximizing the drug dose that can be administered.


J. E. Adair, B. C. Beard, G. D. Trobridge, T. Neff, J. K. Rockhill, D. L. Silbergeld, M. M. Mrugala, H.-P. Kiem, Extended Survival of Glioblastoma Patients After Chemoprotective HSC Gene Therapy. Sci. Transl. Med. 4133ra57 (2012)

Sunday, May 6, 2012

Forget Regret To Enhance Healthy Aging


Healthy aging is associated with reduced response to missed opportunities, that is, emotionally healthy aging is associated with an ability to let go of regrets and not dwell on missed opportunities, according to a study published online April 19 in Science.


Dr. Stefanie Brassen, Ph.D., professor at the University Medical Center Hamburg-Eppendorf in Germany, and her colleagues assessed behavioral and neuronal responses in 21 healthy young adults (mean age, 25.4 years), 20 depressed older adults (mean age, 65.6 years), and 20 healthy older adults (mean age, 65.8 years) while they played an emotionally challenging game. In the game, participants opened a series of boxes containing money or a lost opportunity. If they chose to stop and collect their gains, the box containing the loss was revealed, telling them how far they could have safely continued (missed opportunity).

The researchers found that the healthy young adults and depressed older adults, but not the healthy older adults, took more risks in subsequent rounds of the game when they realized that they could have collected more money. As assessed by functional magnetic resonance imaging, brain activity in the ventral striatum, involved in feeling regret, and in the anterior cingulate cortex, associated with regulating emotion, was similar in young adults and depressed older adults, but differed in healthy older adults. In addition, only younger adults and depressed older adults had increases in skin conductance and heart rate on discovering missed opportunities.

Using a multimodal approach Dr. Prof. Brassen's data show that emotionally healthy aging is associated with a reduced responsiveness to regretful events. Disengaging from regretful experiences at a point late in life where the opportunities to undo regrettable behavior are limited, provide a protective strategy to maintain emotional well-being and thus add a resilience factor to emotional health.

Original Paper:

Title Don’t Look Back in Anger! Responsiveness to Missed Chances in Successful and Nonsuccessful Aging. Science, May, 2012.


Saturday, May 5, 2012

NIH Collaborates With Drug Companies To Reposition Failed Drug Candidates


The National Institutes of Health (NIH) today announced a collaborative program that will match researchers with a selection of pharmaceutical industry compounds to help scientists explore new treatments for patients. NIH's new National Center for Advancing Translational Sciences (NCATS) has partnered initially with Pfizer, AstraZeneca, and Eli Lilly who have agreed to make dozens of their compounds available for this initiative's pilot phase.

In recent years, researchers have succeeded in identifying the causes of more than 4,500 diseases. But translating that knowledge into new therapies has proven difficult, and effective treatments exist for only about 250 of these conditions. NCATS was established last year to help address this gap. The Center supports rigorous scientific research designed to reengineer therapeutic candidates of the development pipeline to move basic research findings into new treatments for patients.

Some compounds do not prove effective for the specific use for which they were developed, however, if additional research is conducted, the compound may succeed for a different therapeutic use. A successful example of a compound that did not prove effective for its initial use but succeeded for a different use is azidothymidine (AZT), which failed to show efficacy against cancer, but was later found to be the first medicine effective against HIV, the virus that causes AIDS.