Micropallet Arrays to Screen and Select Stem Cells

Funding Type: 
SEED Grant
Grant Number: 
RS1-00333
ICOC Funds Committed: 
$0
Disease Focus: 
Amyotrophic Lateral Sclerosis
Neurological Disorders
Spinal Cord Injury
Neurological Disorders
Stem Cell Use: 
Embryonic Stem Cell
Public Abstract: 
The goal of this CIRM seed grant is to extend the potential of a new technology for stem cell studies by bringing to bear state-of-the-art microengineering techniques to the challenges of stem cell screening and selection. The completed system will provide a practical and flexible device with far-ranging applications. The capability to sort cells after experimental manipulation will fuel basic research by providing a means to establish new cell lines for stem cell study. The capabilities of the new instrumentation will enable greater precision and flexibility in the exposure of cells to growth factors to maintain cells in a sem-cell-like state of to differentiate cells into desired tissue types for regenerative medicine. Experiments are envisioned to more accurately recreate developmental events or the functions of stem cell in the living organism. Precise control of the cellular environment along with isolation of precursor cells for the treatment of a particular disorder would have a dramatic impact for medical applications.
Statement of Benefit to California: 
The research to be funded by this CIRM Seed Grant has to potential to directly benefit the citizens of California. The funds will be used to develop a new instrument that stem cell researchers will utilize to test and select unique stem cells for either further study or to grow and apply to medical therapies. The technology has practical and widely applicable uses, so that many researchers in the academic and industrial laboratories of the state will receive benefit through increased efficiency of their studies and the ability to perform new types of experiments to better understand the biology of stem cells and how to use them for regenerative medicine. The research will also stimulate economic development through creation of intellectual property which will be owned by citizens of the California through the state university where the research will take place. This research and that of other investigators funded by these grants will enhance the state’s competitiveness in biotechnology research and development, thus furthering California’s lead in this important area of economic growth.
Progress Report: 
  • A main goal of research in our laboratory is to identify strategies to promote neural repair in spinal cord injury and related neurological conditions. On the one hand, we have been using mouse models of spinal cord injury to study a long-standing puzzle in the field, namely, why axons, the fibers that connect nerve cells, do not regenerate after injury to the brain and the spinal cord. On the other hand, relevant to this CIRM SEED grant, we have started to explore the developmental and therapeutic potential of human embryonic stem cells (hESCs) for neural repair. We do this by first developing a method to genetically manipulate a HUES line of hESCs. The advent of hESCs has offered enormous potential for regenerative medicine and for basic understanding of human biology. To attain the full potential of hESCs as a tool both for therapeutic development and for basic research, we need to greatly enhance and expand our ability to genetically manipulate hESCs. A major goal for our SEED grant-sponsored research is to establish methods to genetically manipulate the HUES series of hESC lines, which are gaining wide utility in the research community due to the advantages on their growth characteristics over previously developed hESC lines. The first gene that we targeted in HUES cells, Fezf2, is critical for the development of the corticospinal tract, which plays important roles in fine motor control in humans and hence represents an important target for recovery and repair after spinal cord injury. By introducing a fluorescent reporter to the Fezf2 locus, we are now able to monitor the differentiation of hESCs into Fezf2-expressing neuronal lineages. This work has been published. A second goal is to start to explore the developmental and therapeutic potential of these cells and cells that derived from these cells in the brain and spinal cord. We are currently utilizing the cell line genetically engineered above to develop an efficient method to differentiate HUES cells into subcerebral neurons. Results so far have been encouraging. Efforts are also underway to overexpress Fezf2 as a complementary approach to drive the differentiation of HUES cells into specific neuronal types. Together, these studies will lay down the foundation for therapeutic development with HUES cells and their more differentiated derivatives for neurological disorders including spinal cord injury where neural regeneration can be beneficial. The CIRM SEED grant has allowed us to pursue a new, exciting path of research that we would have not pursued had we not been awarded the grant. Furthermore, the CIRM funded research has opened a new window of opportunity for us to explore genetic engineering of hESCs to model human neurological conditions in future.

© 2013 California Institute for Regenerative Medicine