Mesoscopic Multimode Molecular Imaging for In Vivo tracking of stem cells
Recent developments in stem cell research suggest that the next revolution in medicine might come from cellular therapies. Transplantation of blood cells has already made a significant impact on the treatment of cancer, but until recently it was inconceivable that we will be able to reconstitute injured organs or regenerate functional tissues. However, it will be neither easy nor soon that we will be able to implement stem cell therapies as standard treatments of disease. One of the major limitations is our poor ability to study the behavior of cells within the body, their natural site of operation. Consequently, extensive experimental approaches are being developed to simulate the events that take place in real life, with quite limited success. It is difficult to imagine quality stem cell therapies without the ability to properly monitor these cells in the body, subsequent to introducing them into the patient.
For achieving their desired revolutionary treatments, we need to better study the mechanisms and spatiotemporal details of stem cell behavior, within a realistic setting. We know that the most primitive stem and progenitor cells are in a low functional state, and require interaction with their specific environment to initiate, direct and control their activity. We also know that the temporal succession of these processes is of outmost importance, as stem cells will react differently when submitted to different sequences of inductive signals. Collecting these data in vivo is much more difficult than otherwise, but given the complexities involved, it is by far the most relevant and efficient path to better understand the functioning of stem cells within the body, and find ways of optimizing it, for therapies as well as safety.
Optical imaging can provide the needed temporal and spatial resolution; however, no commercially available method, no matter how expensive or established, has the requisite performance in vivo. We therefore propose to develop, integrate and use new optical imaging technologies to characterize, in live animals, the behavior of stem cells, down to the molecular level. The needed focus on known molecular interactions, at optimal times requires our new, multimode combination of powerful imaging methods, deployed in concert: hyperspectral (derived from satellite reconnaissance), scattering, fluorescence and coherence, some of which we pioneered. We aim to establish our system as a platform for simultaneous, versatile functional acquisition of information under physiological conditions in real time, to test sequential molecular events in live stem cells, and propose to apply it to investigate important issues, including the interaction of stem cells with their environment, stem cell movement to a specific locus, based on injury or other aberrant physiology, cancer stem cells, and stem-cell based neuroregeneration.
The promise of harnessing stem cells for the treatment of human disease is very exciting, but a lot is required to turn it into reality. Great leaps in technology and in molecular-level understanding of biology are very helpful, but for impacting the way treatments are delivered, more conditions are necessary, strategic, logistic, financial, political. The achievement of true breakthroughs, especially in a massive, heavily regulated field like healthcare, depends on the favorable alignment of a number of circumstances; this is more likely to happen at a state, rather than federal level. To accelerate the pace towards therapies for patients with chronic and debilitating disease and injury, the citizens of California (CA) supported Proposition 71 and the establishment of the CIRM, thus recognizing the fundamental importance of stem cell research to the future of biotechnology and regenerative medicine.
The benefits of any research deemed of high-enough quality by CIRM for funding are likely to be scientific, medical, economic and human, as follows:
1. Fostering better, more goal-directed interdisciplinary science in CA
2. Enhancing CA competitiveness and image in the scientific and medical world
3. Accelerating the path to the cure of important, challenging diseases
1. Addressing - faster, better - problems that are more pronounced in CA (e.g. neurodegenerative diseases, linked to population ageing and overuse of pesticides)
2. Further securing CA’s leading position in biomedical research, biotechnology and potentially in healthcare delivery
3. Attracting relevant research and medical talent to CA
4. Reducing the cost of treating major diseases
III. Additionally, our specific in vivo imaging project, if funded, would contribute as follows:
1. Appling efficient, therapy-relevant investigation and validation methods to important cell lines outside the limits of federally-funded research
2. Developing technologies not likely funded by government, for obtaining data critical to the future of the field and to directing the research strategies of CIRM
3. Transferring to CA-based industry of important technologies that will further strengthen CA’s already leading role in the medical device industry, and creating quality jobs (with positive effects on our tax base)
4. Providing a key ingredient for stem cell therapy validation, standardization and optimization, needed for FDA approval of any therapies (as extensive preclinical testing will be required before these cells are approved for use in humans), and thus
5. Shortening the timelines for delivering cell-based therapies to patients
Our California-invented technology would allow watching some good cellular therapy scenarios unfold in vivo, at a level of spatiotemporal detail that allows subsequent improvements, but also some negative scenarios (immune rejection, teratomas) in their details, in order to learn how to prevent them.