System to generate vascular progenitor cells within naturally constructed (or formed) biomatrices from urine cells.
- Nearly limitless supply of source cells.
- Non-invasive method for harvesting source cells.
- Efficient endothelial cell generation with fewer steps and faster generation time than current standard for differentiating stem cells.
- Ability to generate both endothelial cells and smooth muscle cells from same patient cell source.
- Ability to simultaneously generate biomatrices, which include both endothelial cells and smooth muscle cells.
- Composite construct including both endothelial cells and smooth muscle cells within spontaneously formed biomatrices can be utilized as a patch for therapy.
Ischemic cardiovascular diseases, which includes coronary artery disease and peripheral artery disease, are the most frequent cause of morbidity and mortality in the USA. The main cause of these clinical entities is the loss of blood vessels. Endothelial cells (ECs), as a key element of vasculature, are indispensable for repairing injured or ischemic tissues. Over the years, many approaches have been developed to generate ECs for use in cell therapy. Despite early enthusiasm, adult stem or progenitor cells were found to have minimal endothelial differentiation potential. Embryonic stem cells and induced pluripotent stem cells (iPSCs) emerged as promising alternatives; however, problems such as tumorigenic potential or inefficient cell production have limited their clinical application. Additionally, existing methods for harvesting the source cells for reprogramming are painful and invasive. There is a need to develop non-invasive harvesting systems and more efficient reprogramming methods to generate engineered vasculature. Cell transplantation alone has limitations for cell therapy due to their low cell retention and survival in vivo. Thus, biomaterials are needed to deliver cells to enhance the cell therapy.
Emory researchers have developed an efficient reprogramming system to produce endothelial cells (ECs) and smooth muscle cells (SMCs) using urine stem cells, using a two steps protocol. First, the cells are collected non-invasively from the patient’s own urine followed by reprogramming of these cells using a vascular transcription factor. These reprogrammed tissues containing 30-50% of ECs and a similar percentage of SMCs. Finally, the tissue-like structures are implanted into mouse hindlimb ischemia models, where researchers confirmed the cells within this tissue can be retained for periods longer than 3 months, while all the extracellular matrices are dissolved. This system may serve as a platform for faster and more efficient generation of different types of cells with a tissue-mimicking environment. In this construct, the cells are already embedded in the biomatrices during the reprogramming process. This platform could be used for cell therapy, drug discovery, disease modeling and personalized medicine.
This cellular reprogramming method has been successfully tested in vivo for treatment of ischemic conditions.