Diabetic Foot, Immune Defect
Conditions
Brief summary
The goal of this observational study is to learn about the role of immune cells in patients with diabetes and chronic foot ulcers. Researchers will compare blood and tissue samples of patients with diabetes and a foot ulcer that is healing or healed compared to those diabetic patients where the foot ulcers is not healing (chronic ulcer).
Detailed description
Diabetic foot ulcer (DFU) requires frequent hospital visits, anti-biotic therapies, and surgical procedures. Not only this approach has debilitating consequences for patients and enormous costs for the health care system, but it is often not sufficient to prevent lower limb amputation. The immunological response in wound healing is mainly orchestrated by recruited monocytes and skin macrophages. The current hypothesis is that hyperglycaemia sustains an activated macrophages' phenotype that inhibits wound healing. However, well controlled diabetes is not associated with better healing, and not all the diabetic patients develop chronic foot ulcers. In this project, the investigators aim to characterize the immunological response of patients with DFU to discover new therapeutic targets for the treatment of chronic wounds. The investigator suggest that an altered metabolic local environment can re-program monocytes/macrophages towards dysfunctional phenotypes unable to accomplish the healing process. Here, by using a longitudinal study cohort combined with clinical information, transcriptomic and proteomic analysis at single cell level, researchers will characterize the landscape of monocytes/macrophage populations involved in healing, and non-healing, foot ulcers. Functional validation will be performed in human skin organoids. My group's unique access to patient material combined with cutting-edge methodologies provides an exceptional platform to identify genes and pathways involved in chronic DFU.
Interventions
OTHERmedical treatments
All patients will follow the medical treatments, as recommended by the multidisciplinary clinical team (for example revascularization or ulcer debriding) according to the best standard of care
Sponsors
Karolinska Institutet
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 98 Years
Healthy volunteers
No
Inclusion criteria
* diabetes with diabetic foot ulcer
Exclusion criteria
* impaired cognitive function * on-going immune suppressive treatment * diagnosed active cancer * cancer treatment * known chronic inflammatory disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the longitudinal signature of circulating monocytes in the healing process of diabetic patients | 4 years | An aliquot of peripheral blood mononuclear cells obtained from patients at the first visit will be used to perform single-cell RNA-sequencing. Transcriptomic results of patients with healing ulcers will be compared with those with non-healing ulcers in order to identify different circulating monocytes populations only present in non-healing diabetic patients. |
| Determine the functional contribution of macrophages to diabetic chronic foot ulcers | 4 years | A freshly taken punch biopsy take from patient at visit 1 will be dissociated to a cell suspension. Single cell RNA sequencing analysis will be performed on these cells in order to study different cell populations. Bioinformatic analysis of sequenced data will identify macrophage's population, map cell heterogeneity and identify specific cell signature of healing compared to non-healing ulcers. Moreover, by comparing the transcriptomic signature of the cell populations in the tissue with circulating monocytes population defined in aim 1, researchers will verify whether specific populations are already present in circulation or appearing once the cells are in the tissue, or derived skin-resident macrophages. |
Countries
Sweden
Contacts
Primary ContactEva Steninger
Outcome results
None listed