TCSCP Our Research
Several diseases, such as ischemic heart disease, cerebellar stroke, neurodegenerative diseases, and cancer (solid tumors) share the common denominator hypoxia. In addition to hypoxia, these diseases share a common stress-factor referred to as proteotoxic stress (often due to misfolded proteins). Despite advances made over the past decades, morbidity and death rates still remain very high with these complex diseases. To find new therapies for these diseases, the TCSCP is currently investigating various avenues:
1. Disruptive-assay technology
We have developed a proprietary disruptive assay that can detect various molecular phenotypes guiding cellular decision-making. We are developing and using this assay in high throughput screening of 1000s of molecules to detect and develop drugs for targeting the aforementioned diseases. We are able to exploit cell-decision making via machine learning approaches to guide high throughput screening to detecting the desired drugs. With this possibility, there are amazing and very promising clinical implications for a variety of medical conditions with unmet medical needs.
Our goal for this project is to detect numerous drug that will be developed for clinical utility.
2. Cardiac-specific stem cell-hydrogel system to treat peripheral arterial disease and myocardial infarction (heart attack)
One major problem in ischemia-related diseases such as infarction or peripheral arterial disease is a lack of blood vessels and consequently oxygen, which results in progressive cell death, and consequently patient death or limb amputation. Therefore, as a therapy, it is desirable to create new blood vessels for providing oxygen to damaged regions of such ischemia-related diseases.
In partnership with the University of California, Berkeley, we have developed biodegradable “hydrogels” that help retain stem cells for prolonged time. When combined with cardiac-specific stem cells derived from the patient, the hydrogel converts these cells into new blood vessels. When creating new blood vessels, it is essential that they integrate with the patient’s blood-circulation system. We have shown in animal models that the new blood vessels generated from our cardiac stem cell-hydrogel system can indeed integrate into the host blood circulation system after implantation.
Our aim is to translate these findings into starting clinical trials for treating patients with poor circulatory conditions.
3. Novel bioengineering approaches to create multi-layer collagen sheets for cell transplantation to treat ischemic diseases
We are taking novel approaches in creating multi-layer collagen sheets to use alone or together with stem cells for treating myocardial infarct site and peripheral arterial disease. Various cells such as adult and fetal cardiac and/or neonatal dermal fibroblasts are used to create the sheets. We are exploiting specific cellular-microenvironment sensing mechanisms to entrap specific exosomes and cytokines for creating these therapeutic collagen sheets.
Our aim is to translate these findings into treating patients with ischemia related diseases, where wound healing is crucial.
4. Secreted stem cell factors as novel therapeutic biologics
Data from our cardiac stem cell therapy research has indicated that the beneficial effects we observe after implanting stem cells in a diseased heart are due to secreted stem cell factors. These secreted factors are both neuro- and cardio protective in vitro.
In addition to in vitro data, we have shown clinically in vivo significant rescue of diseased myocardial (heart) cells, with subsequent clinically relevant improvement of heart function by using one of these secreted factors as a therapeutic.
We have started to modify the secreted factors for increasing efficacy during therapy. Additionally, we are delineating the pathways modulated by these cytokines, and applying our findings in high throughput drug screening to detect additional new drugs.
Our goal is to develop the secreted stem cell factors as novel therapeutics to treat ischemia related diseases.
5. 3-D bioprinting of living tissues and organs
With recent advances in technology and biomedical sciences – particularly in molecular biology, bioengineering, and stem cell biology – we have reached a revolutionary and challenging period in 3-D bioprinting, which will change the way we approach medicine in the future.
3-D bioprinting uses 3-D printing technology to create living tissue and organs. A key advantage of 3-D bioprinting is the ability to rapidly produce complex tissue designs from a computer-aided-design file. This makes it possible to use patient images obtained from medical imaging technologies to design identical copies of a patient’s tissues or organs in a three-dimensional space.
We have developed our first printer prototype and are aiming to use a patient’s cardiac stem cells, together with the biodegradable hydrogel, to first create cell patches and eventually print new blood vessels.
Our ultimate goal is to be able to print any organs for transplantation purposes.
6. Exploiting Hypoxia and Anoxia signaling pathways in treating ischemia-related disease
One hallmark of ischemia related diseases is the presence of hypoxia and anoxia. We have discovered novel cellular phenotypes in ischemia and are exploiting the pathways associated with these specific phenotypes for novel therapeutic avenues and strategies, including modulation of stem cell fate for therapeutic efficacy.