Lou Messina Awarded NIH Funding to Study Immune Cell Aging as a Root Cause of Impaired Wound Healing
Date Posted: Tuesday, February 03, 2026
Louis Messina, MD, has received a new NIH R01 award to study why wound healing declines with age and how it may be possible to restore the body’s ability to heal.
Chronic, slow-healing wounds are a major and growing health problem, particularly among older adults and people with type 2 diabetes. As the population ages, these wounds contribute to infections, hospitalizations, and, in some cases, amputations. Dr. Messina’s research seeks to address this problem at its biological root.
A Strong Foundation in Diabetes and Wound Healing
This new work will build directly on decades of NIH-funded research investigating how diabetes and aging impair tissue repair. In earlier studies, the Messina lab demonstrated that people with type 2 diabetes face up to a 25-fold higher risk of limb loss, largely due to impaired wound healing.
In a study they published in Nature Communications (2018), Dr. Messina and colleagues found that the problem begins not in the wound itself, but deep within the hematopoietic stem cells (HSCs) in the bone marrow. These stem cells give rise to immune cells such as macrophages, which play a critical role in coordinating wound repair.
That research showed that in diabetes, excess oxidative stress within HSCs epigenetically reprograms immune cell gene expression. As a result, fewer healing macrophages reach the wound, and those that do are skewed toward a pro-inflammatory state that slows repair rather than promoting it. Transplanting diabetic stem cells into healthy animals was enough to reproduce the impaired wound-healing phenotype, proving that the defect originates in the stem cells themselves.
Earlier work from Dr. Messina’s lab also examined mesenchymal stem cells (MSCs), another promising cell type for regenerative therapies. That study, published in Stem Cell Reviews and Reports (2013) determined that diabetes impairs MSC function, reducing their ability to form new blood vessels and promoting fat cell formation instead. Importantly, his research identified oxidative stress as the key driver of this dysfunction, suggesting that restoring stem cell health could improve healing outcomes.
Turning Attention to Aging—the Strongest Risk Factor
While diabetes is a major contributor to poor wound healing, aging is the strongest risk factor. The new project extends Dr. Messina’s stem-cell framework to aging, asking whether similar mechanisms drive immune dysfunction in older individuals, even in the absence of diabetes.
The study will focus on macrophages and their communication with skin cells such as fibroblasts and keratinocytes, which together determine how effectively a wound closes and regains strength. They will test whether reducing oxidative stress or correcting epigenetic changes in aged stem cells can restore youthful immune function and improve healing.
A Path Toward New Therapies
Restoring the immune system’s ability to heal may help prevent complications before they start. By identifying the molecular switches that drive immune cell aging, Dr. Messina’s work opens the door to therapeutic approaches that could provide clinical advances that improve the lives of people living with diabetes and age-related complications.