A topical cell therapy approach for diabetic chronic ulcers: Effects of mesenchymal stromal cells associated with platelet‐rich plasma

Abstract

Background Diabetic cutaneous ulcers are subjected to several physiological and biochemical defects, which contribute to wound chronicity and therapeutic failure. Platelet‐rich plasma (PRP) has been used for stimulating tissue regeneration, and mesenchymal stromal cells (MSCs) have demonstrated therapeutic properties in all phases of skin regeneration in cell therapy studies. Aims The objective of this study was to evaluate the therapeutic effects related to the use of a biomembrane composed of autologous MSCs and PRP on chronic wounds of diabetic patients (pre‐post pilot study). Patients/Methods Six diabetic patients with chronic wounds for more than 6 months were subjected to adipose tissue collection for isolation of MSCs, blood collection for PRP preparation, and topical administration of a biomembrane of MSCs and PRP on each chronic wound. The statistical difference regarding the evolution of ulcers was calculated by means of paired t test. Results There was granulation tissue formation starting from 7 days after topical application. Total re‐epithelialization occurred in 5 of the 9 lesions treated, and the mean wound healing rate (WHR) was 74.55% (±32.55%) after 90 days. No cicatricial hypertrophy or retraction was observed. Conclusion Mesenchymal stromal cells topical therapy associated with PRP is well‐tolerated and able to provide a reduction in ulcer area of diabetic chronic wounds.

Current Advanced Therapies Based on Human Mesenchymal Stem Cells for Skin Diseases

“…From 2015, eight studies have evaluated the use of hMSCs as a component of TESSs for the treatment of diabetic foot ulcers ( Table 2). Until now, only three of them have published results of safety and effectiveness (Hashemi et al, 2019;Moon et al, 2019;Stessuk et al, 2020). Seven studies evaluated the use of allogeneic hMSCs isolated from adipose tissue (6) or Wharton's Jelly (1) and one study reported the use of autologous hAT-MSCs.…”

“…In all cases, strategy was based on manufacturing sheets of different biomaterials combined with the different hMSCs sources to evaluate their engraftment into diabetic foot ulcers. Those studies with published results applied different hMSCs: allogeneic hWJ-MSCs (Hashemi et al, 2019), allogeneic hAT-MSCs (Moon et al, 2019) and autologous hAT-MSCs (Stessuk et al, 2020). Hashemi et al (2019) evaluated the engraftment of an acellular amniotic membrane seeded with hWJ-MSCs in 5 patients.…”

Effects and mechanism of platelet-rich plasma on military drill injury: a review

“…1 ), so it is widely used in treatment. Investigators found that the local application of mesenchymal stem cells associated with PRP in diabetic chronic ulcers is a well-tolerated therapy and could reduce ulcer size [ 30 ]. Multiple injections of PRP could improve joint function, reduce local pain and synovial inflammation in osteoarthritis patients [ 31 , 32 ].…”

The effect of transcutaneous application of gaseous CO2 on diabetic chronic wound healing—A double‐blind randomized clinical trial

“…Advanced therapeutic options include reducing biofilm and infections, 4 development of different scaffolds for delivering growth factors, nanoparticles, antibiotics, and the use of mesenchymal stromal cells. [5][6][7] Skin substitutes are developed to shorten healing time. Their value is not only in protecting the wound from the risk of infection, but also in delivering added growth factors to enhance healing.…”

“…The results of standard healing methods are often unsatisfactory, therefore, additional and advanced therapeutic options are increasingly being investigated. Advanced therapeutic options include reducing biofilm and infections, 4 development of different scaffolds for delivering growth factors, nanoparticles, antibiotics, and the use of mesenchymal stromal cells 5‐7 . Skin substitutes are developed to shorten healing time.…”