Navigation Links
Method to deliver molecules within embryonic stem cells improves differentiation

Embryonic stem cell therapies have been proposed for regenerative medicine and tissue replacement after injury or disease. However, the inability of stem cells to efficiently develop into the desired specific cell type such as muscle, skin, blood vessels, bone or neurons now limits the potential clinical utility of this therapy.

New research shows that delivering molecules within aggregates of embryonic stem cells via biodegradable microspheres enhances the efficiency and purity of differentiation, which is the process the cells undergo to become more specialized. Details of the microsphere-mediated delivery method, which is funded by the National Science Foundation, were presented on April 9 at the 235th American Chemical Society national meeting.

Directing embryonic stem cells to efficiently differentiate into a specific cell type has been challenging to this point, said Todd McDevitt, an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. In my lab, were trying to better define and then control the environmental cues that regulate the fate and function of the stem cells.

Because physical interactions between stem cells is critical during normal embryonic development, most laboratory growth methods allow the cells to aggregate in three-dimensional clumps called embryoid bodies in order to differentiate. After individual cells aggregate together, hollow internal structures begin to develop and the aggregate becomes larger and more complex over time.

Many researchers add soluble factors to the culture dish medium to direct differentiation, but this does not accurately mimic the time and location of signaling events present in normal development, and may contribute to heterogeneous differentiation, said McDevitt. Our method focuses on incorporating the differentiation factors directly into the cell aggregates in order to have a more controlled mechanism of presentation.

The research team which also includes graduate students Richard Carpenedo and Andrs Bratt-Leal and undergraduate students Ross Marklein and Scott Seaman fabricated biodegradable polymer microspheres that could contain growth factors, proteins or other small molecules.

McDevitts team tested the impact of the poly(lactic-co-glycolic acid) (PLGA) microspheres on embryonic stem cell differentiation under different conditions by varying the microsphere-to-cell ratio and speed at which the aggregate cells were mixed with the microspheres. They also included a fluorescent dye in the microspheres so the degree of incorporation of the microspheres within the embryoid bodies could be assessed using fluorescent microscopy and spectroscopy.

The results revealed that the microspheres were incorporated into embryoid bodies under a variety of mixing conditions, but that slower rotary speeds and higher microsphere-to-cell ratios resulted in a greater degree of incorporation.

Next, the researchers compared differentiation of untreated cells, cells mixed with empty microspheres, cells mixed with retinoic acid-loaded microspheres, and cells treated with soluble retinoic acid. Retinoic acid was chosen initially because it is a potent inducer of embryonic stem cell differentiation.

After ten days, approximately 90 percent of the embryoid bodies mixed with retinoic acid-loaded microspheres began to display the hollow structure signifying differentiation, compared to 6 percent of the untreated bodies, 10 percent of the bodies coated with soluble retinoic acid, and 30 percent of the bodies mixed with empty microspheres. In addition, thirty percent of the embryoid bodies mixed with retinoic acid-loaded microspheres were completely hollow in the center, compared to nearly zero percent for the other groups.

These results suggest that if you can control the signaling by presenting molecules locally on the inside of the embryoid body from biodegradable microspheres, you can effectively change the course and synchrony of differentiation, said McDevitt.

To examine the cells in more detail, McDevitt teamed with Georgia Tech School of Biology chair John McDonald and research scientist Nathan Bowen to conduct microarray gene expression studies to determine cell phenotype.

The results revealed enhanced expression of fibroblast growth factor 5 (FGF-5) a marker for primitive ectoderm in the embryoid bodies mixed with retinoic acid-loaded microspheres compared to the other treatment groups after 10 days. The researchers also confirmed increased or inhibited expression of many additional markers.

The importance of these findings is that weve shown that biomaterial-based approaches to regulate stem cell microenvironments can significantly improve differentiation methods, said McDevitt. Our ultimate goal is to improve the efficiency of this differentiation process into specific cell types for cell replacement therapies.


Contact: Abby Vogel
Georgia Institute of Technology Research News

Related biology technology :

1. International Scientific Workshop Focuses on New Methods for Vaccine and Antibody Development
2. NIST team develops novel method for nanostructured polymer thin films
3. Nanofabrication method paves way for new optical devices
4. New method of selecting DNA for resequencing accelerates discovery of subtle DNA variations
5. NIST develops test method for key micromechanical property
6. Scientists discover new method of observing interactions in nanoscale systems
7. Newly Published EPA RCRA Method 6800 Supports AIT Technology
8. Attagenes Breakthrough Transcription Factor Profiling Technology to be Described in Nature Methods
9. Cellular construction methods emulated
10. Proteon Therapeutics Receives European Patent Covering New Method of Dilating Arteries and Veins
11. Anesiva Grants Specific-Use License of Its Needle-Free Drug Delivery Technology to Particle Therapeutics for Diabetes Drug
Post Your Comments:
Related Image:
Method to deliver molecules within embryonic stem cells improves differentiation
(Date:6/24/2016)... ... ... While the majority of commercial spectrophotometers and fluorometers use the z-dimension of 8.5 ... end machines that use the more unconventional z-dimension of 20mm. Z-dimension or ... the cuvette holder. , FireflySci has developed several Agilent flow cell product lines ...
(Date:6/23/2016)... ... June 23, 2016 , ... UAS ... the launch of their brand, UP4™ Probiotics, into Target stores nationwide. The company, ... proud to add Target to its list of well-respected retailers. This list includes ...
(Date:6/23/2016)... 2016 A person commits a crime, and the ... track the criminal down. An outbreak of foodborne ... Administration (FDA) uses DNA evidence to track down the bacteria ... far-fetched? It,s not. The FDA has increasingly used a complex, ... foodborne illnesses. Put as simply as possible, whole genome sequencing ...
(Date:6/23/2016)... MONICA, Calif. , June 23, 2016  The Prostate Cancer Foundation ... pioneer increasingly precise treatments and faster cures for prostate cancer. Members of the ... institutions across 15 countries. Read More About the Class ... ... ...
Breaking Biology Technology:
(Date:6/2/2016)... June 2, 2016 The Department of ... awarded the 44 million US Dollar project, for the ... Plates including Personalization, Enrolment, and IT Infrastructure , ... the production and implementation of Identity Management Solutions. Numerous renowned ... Decatur was selected for the most ...
(Date:6/1/2016)... , June 1, 2016 ... in Election Administration and Criminal Identification to Boost Global ... a recently released TechSci Research report, " Global Biometrics ... Region, Competition Forecast and Opportunities, 2011 - 2021", the ... billion by 2021, on account of growing security concerns ...
(Date:5/16/2016)... NEW YORK , May 16, 2016   ... authentication solutions, today announced the opening of an IoT ... to strengthen and expand the development of embedded ... provides an unprecedented level of convenience and security with ... to authenticate one,s identity aside from DNA. EyeLock,s platform ...
Breaking Biology News(10 mins):