Mesenchymal stromal cells therapy alone does not lead to the complete restoration of the skin parameters in diabetic foot patients within a 3-year follow-up period

Abstract

Introduction: Mesenchymal stromal cells (MSCs) administration is an effective option for the treatment of diabetic foot ulcers (DFUs). However, to date, studies assessing long-term outcomes and evaluating skin parameters after cell-based therapy are lacking. We presented the clinical outcomes of 3 patients, treated for DFUs with the bone marrow MSCs 3 years earlier. Methods: Ultrasound examination was used to compare collagen density and epidermal thickness in areas of healed ulcers in comparison with non-affected skin used as a control. Ultrasound and dermatoscopy were used to exclude neoplasm formation, to assess scar contracture and wound recurrence. Results: In all patients, no ulcer recurrence was detected, which was lower than the expected 60% rate of re-ulceration in diabetic patients in a 3-year period (OD [odds ratio] = 0.095, P = 0.12). No neoplasm formation, no contracture of hypertrophic scar, and adjacent tissue were registered. Collagen ultrasound density was decreased by 57% (P = 0.053) and epidermal thickness was increased by 72% (P = 0.01) in the area of healed ulcers in all patients. Conclusion: MSCs therapy alone did not result in the complete restoration of the skin parameters within a 3-year period. MSCs may represent important adjuvant to the therapy, however, other novel approaches are required to achieve better results.

Adverse events, side effects and complications in mesenchymal stromal cell-based therapies

“…Thus, loss of vision was a negative reaction to adipose-derived MSC therapy in three patients with age-related macular degeneration ( 63 ). In another study, MSCs therapy alone does not lead to the full-thickness restoration of ulcerated skin after topical administration ( 64 ). The effectiveness of adipose- and bone marrow-derived MSC in the treatment of lateral amyotrophic sclerosis is also controversial.…”

Tissue Sheet Engineered Using Human Umbilical Cord-Derived Mesenchymal Stem Cells Improves Diabetic Wound Healing

“…Furthermore, the long-term outcomes and the effectiveness of MSC-based cell therapies still need to be improved. Maksimova’s and Zhang’s studies showed that topical administration of MSCs is a safe and promising option, but it took effect mainly in the initial wound closure at an early stage [ 39 , 40 ]. Here, we provide a new method to enhance the effectiveness of MSCs and maybe improve the long-term outcomes in the future.…”

Intraoperative Creation of Tissue-Engineered Grafts with Minimally Manipulated Cells: New Concept of Bone Tissue Engineering In Situ

“…At the same time, some studies show that there are no strong correlations between the amount of administered cells and the therapeutic effect [ 140 ]. In fact, recently, in vitro cultured cells exerted promising therapeutic results when administered at low doses of less than 40 × 10 3 cells per 1 cm 2 of a skin wound surface [ 141 ]. Interestingly, in a rat critical-sized bone defect, seeding of β-TCP with minimally manipulated BM-MNCs increased the volume of a newly formed bone, however, seeding of 5 × 10 6 cells led to more pronounced bone formation compared to 1 × 10 7 cells, and the highest mineral bone density was observed in β-TCP seeded with 1 × 10 6 cells [ 140 ].…”