Improving Stem Cell Therapies that Promote Blood Vessel Generation in Ischemic Tissue
Stem cell therapies are one of the approaches to treating progressive loss of blood flow to tissues, such as results from severe atherosclerosis, in which important blood vessels are narrowed or even blocked. Unfortunately first generation stem cell therapies are variable in outcome, cellular senescence in cell cultures prior to transplantation is poorly controlled, and the transplanted cells die quite quickly. Thus even though the benefits of treatment arise from signaling generated by transplanted cells, rather than cell integrating into tissues, there is much that can be improved. One of the ways in which researchers are producing that improvement is via the use of scaffold materials to extend the lifespan of transplanted cells and better steer their behavior, as illustrated here.
Critical limb ischemia is a condition in which the main blood vessels supplying blood to the legs are blocked, causing blood flow to gradually decrease as atherosclerosis progresses in the peripheral arteries. Current treatments include angioplasty procedures such as stent implantation and anti-thrombotic drugs, but there is a risk of blood vessel damage and recurrence of blood clots, which is why there is a strong interest in developing a treatment using stem cells.
Stem cell therapies have high tissue regeneration capabilities, but when stem cells are transplanted alone, hypoxia at the site of injury, immune responses, and other factors can reduce cell viability and prevent the desired therapeutic effect. Therefore, it is necessary to develop a material that delivers stem cells using biodegradable polymers or components of extracellular matrix as a support to increase cell viability.
Researchers processed collagen hydrogels to micro-scale to create porous, three-dimensional scaffolds that are easy to inject in the body and have a uniform cell distribution. Collagen, a component of the extracellular matrix, has excellent biocompatibility and cellular activity, which can induce cell self-assembly by promoting interactions between the microgel particles and collagen receptors on stem cells. In addition, the spacing between microgel particles increased the porosity of the three-dimensional constructs, improving delivery efficiency and cell survival.
The microgel-cell constructs developed by the researchers expressed more pro-angiogenic factors and exhibited higher angiogenic potential than cell-only constructs. When microgel-cell constructs were injected into the muscle tissue of mice with critical limb ischemia, blood perfusion rate increased by about 40% and limb salvage ratio increased by 60% compared to the cell-only constructs, confirming their effectiveness in increasing blood flow and preventing necrosis in the ischemic limb.