Preprint: a meta-analysis of 68 mouse studies linked vascular cells to improved blood flow; integration of these cells into vessel walls showed no association with the effect
Preprint: a meta-analysis of 68 mouse studies linked vascular cells to improved blood flow; integration of these cells into vessel walls showed no association with the effect
A preprint published on September 9 pooled 68 preclinical studies of vascular cells derived from pluripotent stem cells. In the primary analysis of 51 studies with 114 comparisons, tissue blood flow after cell therapy was on average 1.96 times higher than in control groups.
Limb ischemia occurs when blood reaches tissues poorly and they lack oxygen. In the laboratory, pluripotent stem cells can be turned into various specialized cell types; in these experiments they were used to generate vascular cells, including endothelial cells that line the inner surface of blood vessels. Researchers injected these cells into mice with impaired limb blood supply to help the vascular network recover.
In such experiments, two distinct things need to be assessed: whether tissue blood flow increased, and whether the transplanted cells became part of the vessel wall through which blood flows. The review authors analyzed these outcomes separately. The collected studies varied in animal model and measurement method, so the pooled estimate describes the field as a whole rather than any single standardized experiment.
Transplanted cell integration into the vessel wall was tracked in 35 of the 68 studies. Seven studies demonstrated blood flowing through vessels that contained donor cells. The analysis found no association between the degree of such integration and improvement in blood flow.
The review authors recommend that future preclinical experiments measure blood flow in a blinded fashion, distinguish between host mouse and donor cells, and verify flow through vessels containing transplanted cells. Such a design connects outcome measurement with verification of the mechanism behind it.
In August, KadisBio reported that, together with Severance Hospital, it administered endothelial cells grown from induced pluripotent cells (blood cells reprogrammed in the laboratory) to the first patient with peripheral artery disease. This early-stage study is primarily assessing safety; investigators also plan to monitor blood flow, pain, wound healing, and amputation risk.