|Attending the recent Quan-tum program meeting were (front, from l) Drs. Mary Dickinson and Karen Hirschi of Baylor College of Medicine; Dr. Anthony Atala of Wake Forest University; NIBIB director Dr. Roderic Pettigrew; Dr. Raoul Kopelman of the University of Michigan; Dr. Mehmet Toner of Massachu-setts General Hospital. At rear are (from l) Drs. Shuvo Roy and William Fissell of Cleveland Clinic; Dr. Daniel Orringer of the University of Michigan; NIBIB Extramural Science Program director Dr. William Heetderks; NIBIB Quantum Grant project officer Dr. Albert Lee.
The National Institute of Biomedical Imaging
and Bioengineering recently held its first “Quantum” grantee meeting. The goal of the high-impact, high-risk Quantum Program is to make a profound advance in health care by solving
or substantially improving targeted major health care problems within approximately 10 years. NIBIB director Dr. Roderic Pettigrew likens
these research projects to “medical moon shots.” The meeting brought together the grantees
and NIH staff to share initial successes and future plans.
Circulating Tumor Cells Captured: Preventing Metastases
Microelectromechanical systems (MEMS) technology
is the basis for fabrication of a microchip that may greatly improve the early detection of cancer cells circulating in the blood and help determine the effectiveness of targeted therapy. Microfabricated posts within the point-of-care device are coated with antibodies that specifically
bind to proteins on the surface of circulating
tumor cells (CTCs). Remarkably, most of the targeted cancer cells stick to the posts while billions of other cells in the blood pass by. These cells are so rare (they are found at levels of one cancer cell in a billion normal cells) that locating one is like “finding a needle in a moving
haystack,” notes Dr. Mehmet Toner of Massachusetts
General Hospital. Early detection of CTCs may allow prevention of metastatic disease,
which is the cause of death in 90 percent of cancer patients.
Stem Cell Therapy: Prospects for Stroke and Diabetes
A treatment that restores lost function to the almost 700,000 victims of stroke is the broad conceptual goal of Dr. Karen Hirschi’s team at Baylor College of Medicine. Her group aims to recreate the brain regions involved in the generation
of new neurons—neurogenesis niches—
and transplant them into brain areas affected by stroke. Using sophisticated imaging
techniques and complex analysis software, her research team has laid the groundwork for this effort by mapping cell-cell and cell-matrix interactions in neurogenesis niches, defining the neurovascular architecture and characterizing
the blood flow dynamics that stimulate and support neural stem cell function. A three-dimensional blueprint of such a niche is under development.
Dr. Anthony Atala of Wake Forest University is working on using stem cells collected from amniotic fluid to treat diabetes by regenerating
pancreatic beta cells. Amniotic fluid stem (AFS) cells are self-renewable and have the ability to differentiate
into numerous tissues.
“Unlike human embryonic stem cells, AFS cells do not form tumors and retain a normal genetic phenotype,”
says Atala. Undifferentiated AFS cells transformed with the Pdx1 gene—critical for pancreatic cell development—can generate pancreatic
islets and produce insulin. When injected into diabetic mice, these cells can restore glucose regulation. The next step is to demonstrate that this can be done in primates as well.
Nanoparticles to Define and Eliminate Brain Tumors
Despite progress in treating many cancers, treatment
of malignant brain tumors remains a daunting challenge. Surgical removal of malignant
brain tumors is often incomplete due to the inability to visually distinguish between healthy and cancerous tissue and the undetected tumor projections into healthy tissue. To address these problems, Dr. Raoul Kopelman of the University
of Michigan is developing multifunctional nanoparticles that carry components capable of selectively targeting and visibly marking tumor cells, allowing for improved surgical resection. A therapeutic agent on the nanoparticle will be used to kill residual tumor cells using laser-activated
photodynamic therapy. This technology will address a critical roadblock that has long hindered
the successful treatment of brain cancer.
Dialysis May Give Way to Artificial Kidneys
Hemodialysis and renal transplants are the treatments
of choice for people with kidney failure. However, Dr. Shuvo Roy of the Cleveland Clinic is developing the next best thing—an implantable device that replaces kidney function. The artificial
kidney has two key components: a hemofilter that filters toxins from the blood, and a bioreactor
with living kidney tubule cells that pumps filtered water and necessary salts back into the blood. The filtration membrane of the device is being developed using MEMS technology. Precise control of size, density and distribution of pores on the membrane enables blood filtration within the body.