TY - JOUR

T1 - Novel topical allogeneic bone-marrow-derived mesenchymal stem cell treatment of hard-to-heal diabetic foot ulcers

T2 - a proof of concept study

AU - Askø Andersen, Jonas

AU - Rasmussen, Anne

AU - Frimodt-Møller, Marie

AU - Engberg, Susanne

AU - Steeneveld, Esther

AU - Kirketerp-Møller, Klaus

AU - O’Brien, Timothy

AU - Rossing, Peter

N1 - Publisher Copyright: © 2022, The Author(s).

PY - 2022

Y1 - 2022

N2 - Aim: The aim of this study was to investigate safety of treating diabetic foot ulcers with a topically administered mesenchymal stem cell product. Method: Individuals with diabetes, peripheral neuropathy, toe blood pressure > 39 mmHg and non-infected foot ulcers with duration of four to fifty-two weeks were screened. Participants were treated with a one-time application of a topically applied allogeneic cellular product containing CD362 enriched mesenchymal stem cells suspended in a collagen solution. Participants were subsequently followed for seven months to gather information on adverse event and serious adverse events. Results/discussion: A total of sixteen individuals were screened, of whom two were included. The included participants incurred a total of seven adverse events and one serious adverse event. Increased exudation from the treated diabetic foot ulcer was observed for both participants and a connection to investigational medicinal product was suspected. The increased exudation was resolved within one week after application of investigational medicinal product, without any further complications. The serious adverse event consisted of a hospital admission due to neurological symptoms, which were assumed to be caused by hypoglycemia, with no suspected correlation to the investigational medicinal product. None of the other observed adverse events were suspected to be associated with the investigational medicinal product. Conclusion: This study presents data from two individuals with a diabetic foot ulcer treated with a novel topical mesenchymal stem cell product. An adverse event observed for both participants was suspected to be associated to the investigational medicinal product, i.e., increased exudation, which was resolved within one week, did not lead to further complications and can easily be remedied by choosing bandages with higher absorption capacity or increasing frequency of bandage changes. This study lays the groundwork for further large scale randomized clinical studies. Trial registration: EudraCT number 2015-005580-16. Registered 12/06-2018.

AB - Aim: The aim of this study was to investigate safety of treating diabetic foot ulcers with a topically administered mesenchymal stem cell product. Method: Individuals with diabetes, peripheral neuropathy, toe blood pressure > 39 mmHg and non-infected foot ulcers with duration of four to fifty-two weeks were screened. Participants were treated with a one-time application of a topically applied allogeneic cellular product containing CD362 enriched mesenchymal stem cells suspended in a collagen solution. Participants were subsequently followed for seven months to gather information on adverse event and serious adverse events. Results/discussion: A total of sixteen individuals were screened, of whom two were included. The included participants incurred a total of seven adverse events and one serious adverse event. Increased exudation from the treated diabetic foot ulcer was observed for both participants and a connection to investigational medicinal product was suspected. The increased exudation was resolved within one week after application of investigational medicinal product, without any further complications. The serious adverse event consisted of a hospital admission due to neurological symptoms, which were assumed to be caused by hypoglycemia, with no suspected correlation to the investigational medicinal product. None of the other observed adverse events were suspected to be associated with the investigational medicinal product. Conclusion: This study presents data from two individuals with a diabetic foot ulcer treated with a novel topical mesenchymal stem cell product. An adverse event observed for both participants was suspected to be associated to the investigational medicinal product, i.e., increased exudation, which was resolved within one week, did not lead to further complications and can easily be remedied by choosing bandages with higher absorption capacity or increasing frequency of bandage changes. This study lays the groundwork for further large scale randomized clinical studies. Trial registration: EudraCT number 2015-005580-16. Registered 12/06-2018.

KW - Clinical trial phase I

KW - Diabetic foot

KW - Mesenchymal stem cells

KW - Safety

U2 - 10.1186/s13287-022-02951-8

DO - 10.1186/s13287-022-02951-8

M3 - Journal article

C2 - 35765085

AN - SCOPUS:85133031594

VL - 13

JO - Stem Cell Research & Therapy

JF - Stem Cell Research & Therapy

SN - 1757-6512

IS - 1

M1 - 280

ER -