Mechanisms Behind Impaired Wound Closure in Elderly Burn Patients

Author(s):
Abdikarim Abdullahi; Marc Jeschke; Robert Yao; Nancy Yu; Saeid Amini-Nik

Background:

Advancements in burn care, such as early excision and grafting, and adequate nutrition to curtail post-burn hypermetabolism, have markedly decreased themortality of paediatric and adult burn patients over the last three to four decades. Despite these major advances, burn patients over the age of 65 years still have unacceptability higher mortality rates, with the Lethal Dose 50 (LD50) in this population remaining unchanged in the last three decades. Impaired skin wound healing has been implicated in mediating poor outcomes in elderly burn patients, as it both facilitates persistent hypermetabolism and increased risk of infection. However, the underlying mechanisms responsible for impaired wound closure in this sup-population remains unclear.

Hypothesis:

We hypothesize that delayed wound healing in the elderly after a burn injury, is likely due to alterations in the characteristics of progenitor cells in the skin of these patients.

Methods:

To unravel the mechanisms of deficient wound closure after a burn injury, we compared skin-healing characteristics of Young (8weeks old) and Aged mice  (>52 weeks) subjected to 30% full thickness burn that was monitored up to two weeks post burn injury.Additionally, we assessed both the migratory capacity and stem cell progenitor pools in skin derived from elderly and adult burn patients admitted to the Ross Tilley Burn Center.

Results:

Here, we show that skin from aged post-burn mice are deficient in mesenchymal progenitor cells marker (Sca-1) and show impaired migration to the wound bed. Similarly, skin from elderly burn patients show impairments in wound healing due to profound changes in their stem cell niche such as blunted responsiveness to tissue injury (deficient migration of mesenchymal stem cells (MSCs) and a decline in mesenchymal progenitor cells (Stro-1 positive) in their skin.  Taken together, our clinical and rodent findings suggest that impaired wound closure in the elderly after a burn injury is mediated by reduced stem cell pool and deficient migration of MSCs to the wound bed.

Conclusions:

Our data provide insights into the mechanisms behind impaired wound closure in elderly patients after a burn injury, and in this context, suggest therapies that exert a dual function – namely increasing MSC proliferation and migration to improve healing.