Bone marrow-derived fibroblasts in skin wound healing

Project: Research project

Project Details

Description

Bone marrow-derived fibroblasts in skin wound healing.
Nearly 25% of all diabetic patients, with foot ulcers, will inevitably progress to major limb amputation.
Diabetic wound healing deficiencies are associated with impaired tissue level neovascularization, impaired
keratinocyte function, reduced tensile strength, and higher infection rates. While these generalized poor
wound healing defects of patients with diabetes mellitus are well established, the specific tissue level
mechanisms responsible for these wound-healing deficiencies remain poorly understood. A complex cellular
cascade mediates normal cutaneous wound healing, where all skin cells cooperate to repair and rebuild the
dermis and epidermis. But in patients with chronic wounds, these signals for cell recruitment, proliferation,
and differentiation in the wound bed are disrupted. Overall, we aim to develop new strategies for treating
chronic leg wounds by primarily identifying specific molecules, that when expressed by cells within the
wound itself, will promote healing of chronic wounds as well as fully restore skin architecture and function.
Because fibroblasts are the critical cell type for early and late wound healing, we hypothesize that, during
normal wound healing, fibroblast precursor cells are recruited from both, the resident resting pool in the skin
and the bone marrow-derived stem cell populations, which then subsequently migrate into the wound bed
and differentiateinto mature fibroblasts. To distinguish between these two cellular populations we have
developed in vivo bone marrow transplantation models, using normal and diabetic mice, and novel in vitro
three-dimensional reconstructions of human dermis, vascularized dermis, and skin, in which fibroblasts can
interact with other key cell types involved in wound healing. In these in vivo wound-healing models and in
vitro reconstructionswe will determine the extent to which bone marrow-derived fibroblasts influence wound-
healing processes including contraction of collagen, stimulation of vessel formation, re-epithelialization and
keratinocyte growth and differentiation. With the use of viral vector delivery of agonists and inhibitors, we will
test the hypothesis that growth factors, specifically PDGF-B (platelet-derived growth factor) are critical for the
activation of bone marrow-derived fibroblasts to invade into collagen, proliferate, migrate to the wound,
survive, and differentiate into long-term cellular components of the healed skin wound.
StatusFinished
Effective start/end date3/15/062/28/11

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases: $129,787.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $269,344.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $155,601.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $265,333.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $126,875.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $290,450.00
  • National Institute of Diabetes and Digestive and Kidney Diseases: $266,651.00

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.