Cellular Patch That can be Prepared in the Operating Room Helps Hearts Heal After Ischemic Injury

by Amanda Chase, PhD
October 16, 2025

Heart attacks leave behind injured heart muscle that the body cannot fully repair on its own, leaving the damaged area weak, poorly supplied with blood, and prone to scarring. Healing damaged heart muscle remains a critical need to improve patient health. A team at Stanford University sought to address this problem directly at the site of injury by creating a living “CC patch” that can be laid over the damaged region to help it heal. Led by co-first authors and Stanford Cardiovascular Institute members Eric Pfrender, Sungwoo Kim, and John Farag, with senior authors Yunzhi Peter Yang and Yasuhiro Shudo, the researchers designed a patch that brings both the right cells and the right support structure to the heart’s surface when needed. Their innovative findings were recently published in Stem Cell Translational Medicine.

To build the patch, the team mixed two types of human blood vessel-forming cells (endothelial progenitor cells, which line blood vessels, and smooth muscle cells, which strengthen and stabilize them) into a medical-grade collagen solution. Within minutes, the solution forms a soft gel. The researchers then gently compress to squeeze out water. This “plastic compression” creates a thin, flexible, and surprisingly strong collagen sheet packed with living cells. The whole process takes less than an hour, producing a patch that surgeons can lift, bend, and place directly onto the injured area without it falling apart.

Overview of cellular collagen “CC” patch. The team created a strong collagen sheet packed with living cells that can be placed on the injured area. They evaluated the recovery of those with the CC patch compared to those without a CC patch and found functional gains from the patch.

In preclinical studies of heart attack, animal models treated with the cellular CC patch showed clearer signs of recovery than those given a collagen patch without cells or no patch at all. Most importantly, the hearts that received the living patch pumped blood more effectively over the following weeks, a sign that the damaged muscle was functioning better rather than continuing to decline. These functional gains were also accompanied by healthier remodeling of the injured tissue, consistent with the patch helping the heart heal rather than scar.

A key question was whether the transplanted human cells would truly engage with the host heart.

The team tracked the cells after surgery and found that they did not just sit on the surface. Many moved into the nearby heart muscle, especially along the border of the injured region where help is needed most. There, the human endothelial progenitor cells appeared around small blood vessels, and smooth muscle cells contributed to vessel support, evidence of direct participation in rebuilding the local microcirculation. The cells also persisted for weeks, long enough to influence the repair process. Alongside this “direct” incorporation, the cells likely released helpful signals that encouraged the heart’s own cells to form new vessels and resist further injury.

To further understand these effects, the researchers analyzed gene activity patterns, a technique called transcriptomics, in heart tissue exposed to the cellular patch versus controls. This molecular readout pointed to a coordinated shift toward healing: genes linked to new blood vessel growth and tissue protection were more active, while programs associated with excessive scarring and harmful inflammation were toned down. This suggested that the living patch both added cells and rewired the local biology in a way that supports recovery.

Current standard treatments do not directly address the fragile, under-perfused tissue left behind after a heart attack; this living patch offers a practical new way to fill that need. This rapidly made, easy-to-handle collagen sheet carrying carefully chosen human vascular cells can be placed on the heart soon after a heart attack. Those cells take hold at the edge of the injury, help build and stabilize new blood vessels, and send signals that nudge the surrounding tissue toward repair. This important work has the potential to help patients recover strength after ischemic injury.

Other Stanford Cardiovascular Institute researchers contributing to the study include Shin Yajima, Yujiro Kawai, Koji Kawago, Umayr Syed, Gentaro Ikeda, Tsuyoshi Ueyama, Hiroyuki Takashima, Alex Dalal, Yuanjia Zhu, Kenzo Ichimura, Yu Liu, Seyedsina Moeinzadeh, Jayme Koltsov, Joseph Wu, Joseph Woo, and Phillip Yang.