Progenitor cell therapy for sacral pressure sore: a pilot study with a novel human chronic wound model

Abstract

Introduction: Chronic wounds are a major health-care issue, but research is limited by the complexity and heterogeneity in terms of wound etiology as well as patient-related factors. A suitable animal model that replicates the situation in humans is not available. Therefore, the aim of the present work is to present a standardized human wound model and the data of a pilot study of topically applied progenitor cells in a sacral pressure sore.

Methods: Three patients underwent cell harvest from the iliac crest at the time of the initial debridement. Forty-eight hours after bone marrow harvest and debridement, the CD34+ selected cell suspension was injected into the wound. With the aid of a laser scanner, three-dimensional analyses of wound morphometry were performed until the defect was reconstructed with a local flap 3 weeks after debridement.

Results: Decreases in volume to 60%±6% of baseline on the sham side and to 52%±3% of baseline on the cell side were measured. Histologic work-up revealed no signs of metaplastic, dysplastic, or neoplastic proliferation/differentiation after progenitor cell treatment. CD34+ cells were detected in the biopsies of day 0.

Conclusions: The pressure sore wound model allows investigation of the initial 3 weeks after cell-based therapy. Objective outcome analysis in terms of wound volume and histology can be performed without, or with, minimal additional morbidity, and the anatomy of the sacral area allows a control and study side in the same patient. Therefore, this model can serve as a standard for wound-healing studies.

Trial registration: ClinicalTrials.gov NCT00535548.

Figures

Figure 1

Mapping of the pressure sore 48 hours after debridement with the planned injections sites for the stem cells on the left side. (a) The stem cell solution is used on one side of the pressure sore, and a sham solution is used on the other side (at a distance of 1 cm in radius around injection sites). The midline can easily be identified by orientation of anatomical landmarks (rima ani, spine, or the anus). For the sake of clarity, the injection points on the control side are not included in the picture. (b) Injection of the progenitor cells.

Figure 2

Biopsy at day one confirming the presence of CD34+ progenitor cells marked in brown (immunohistochemical reaction with intrahepatic leukocyte-4 (IHL-4). Magnification 20×.

Figure 3

Decrease in the volume of the wound on the control side (dotted line) and the stem cell side (continuous line) normalized to the values of day 5 (mean ± standard deviation). D, day.

Figure 4

Laser scanning images of the same pressure sore. Image-processed scans of a treated pressure sore (a) after treatment and at (b) 5 days, (c) 12 days, and (d) 19 days.