Novel Topical Allogeneic Bone-Marrow Derived Mesenchymal Stem Cell treatment of Hard to Heal Diabetic Foot Ulcers

This was a single center open label phase IIb study on the safety of a novel single application topical stem-cell treatment for diabetic foot ulcers.
It is a well described fact that diabetic foot ulcers are a large challenge for both persons with diabetes and the society in general and even though we have made strides in treating diabetic foot ulcers there is still a large unmeet need for new treatments.
One of the new treatment options that have shown promise is stem-cells. There are several tissues that can supply stem-cells, i.e. fat, umbilical cord and blood. However, the tissue that has shown the most promise is bone-marrow, where several studies have shown promise.
In this study we recruited individuals with diabetes and a diabetic foot ulcer for treatment with the investigated medical treatment. A total of 16 individuals were identified, but only two meet all inclusion and exclusion criteria and accepted enrollment in the study.
The investigated product was an allogenic cellular therapy product containing mesenchymal stem cells suspended in a hypothermasol formulation. The stem-cells was donated by and harvested from healthy adult non-related leucocyte antigen unmatched donors. Before application stem-cell product was mixed with a 6.5% collagen solution.
Enrolled participants were subsequently observed in a run-in period to ensure that ulcer did not heal on standard treatment before application. A single application of the investigated product was performed in a specialized phase I unit. Participants were subsequently followed closely for 24 weeks where adverse events and ulcer details where observed.
Two participants completed the study according to protocol. Both were male, with type 2 diabetes with diabetes durations of 6 and twelve years respectively.
Participant one incurred four adverse events and one serious adverse event, while participant 2 incurred three adverse events and no serious adverse events. Of the 8 adverse events incurred in total, one was potentially linked to the treatment and was shared by both participants namely increased exudation from the ulcer in the first week after application. The increased exudation is a potential serious problem as it can lead to maceration of the ulcers. However, the increased exudation was resolved within one week, didn’t lead to any long og short term damage and did not reoccur. In addition, the increased exudation can be remedied by change in choice and/or changing frequency of bandages.
None of the treated ulcers healed during follow-up, but this study was neither designed or powered to examine ulcer healing
This study presents safety and tolerability of a novel stem-cell treatment option for the diabetic foot ulcer. Stem cell treatment of the diabetic foot ulcer is not available to the general public. Most stem-cell treatments require a large set-up for harvesting and preparing the product as it is harvested from the treated individual. If the cells chosen for treatment is bone-marrow the harvesting of the cells poses several challenges i.e. placing patients in a hypercoagulable state, performing an invasive procedure, and exposing patients to epidural procedure and sedation.
The investigated product promises to solve some of theses challenges, as it is harvested from healthy donors and send to treatment center in ready to apply form and is topically applied.
Large scale studies are still needed but this small study supports that this novel stem-cell product is a safe treatment option for diabetic foot ulcers.