1. Fig 1: Microscopic Spindle shaped MSCs Fig 2: Method of MSCs Injection
Autologous Mesenchymal Stem Cells In Treatment of Recalcitrant Neuropathic Diabetic Foot Ulcer: Randomized Controlled Trial
P07
Ahmed Albehairy, Hassan Abdelghaffar,*,Hala Abdelhafez, Ahmed Emam.**, Mahmoud Elhoussiny **, Manal Tarshoby
Department of Internal Medicine,*Department of Clinical Pathology, **Biochemist at Mansoura Experimental Research Centre(MERC).
Faculty of Medicine, Mansoura University
Introduction
Results
Nearly 10–15% of ulcers will remain resistant to treatment (recalcitrant ulcer) and 5–24% of them will finally lead to limb amputation within a period of 6–18 months after the first evaluation. (1)
Diabetic wounds are associated with chronic inflammatory environment and persistent increase in pro-inflammatory cytokines. It was proven that this blunts the acute, focused cytokine response required for the normal phases of healing of diabetic wound (2)
Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. (3)
Stem cell therapy emerged as a new solution added to the modalities of treatment aiming to reverse the underlying diabetic foot ulcer pathophysiology (4).
Safety and efficacy of bone marrow derived mesenchymal stem cells (BM-MSCs) were confirmed for enhancing DFU healing in diabetic patients with diabetic critical limb ischemia compared with bone marrow derived mononuclear cells (5)
Ulcer sizes were described in median (range). In the group of MSCs ulcer size decreased by median 49.9%(9.09%,86.6%) after 6 weeks and reached 68.24% (3.03%-100%) after 12 weeks while the conventionally. treated group ulcer sizes reduction were 7.67% (-30%-35%) after 6 weeks and reached 5.27% ( %- 25%) after 12 weeks .(P value < ). Complete healing was achieved in one case in MSCs group (Fg.3) and another case after 16 weeks (Fig.4). There were no systemic complications or local reactions to the stem cell therapy
(Fig 3).
(Fig 4).
2weeks
4weeks
6 weeks
Day 0
Aim of the work
12 weeks
8 weeks
To study the effect of locally injected autologous bone marrow mesenchymal stem cells (BM MSCs) on ulcer healing in patients with resistant neuropathic diabetic foot ulcers
4 weeks
Day 0
2 weeks
Subjects and methods
Twenty patients with resistant neuropathic diabetic foot ulcers were randomly assigned to conventional treatment and proper offloading modalities alone or with added MSCs injection. Aspiration of 40 cc of patients’ own bone marrow under good aseptic technique was done. MSCs were characterized by adherence and trans-differentiation (Fig 1).. Cultured cells were subjected to microbiological and karyotyping testing, then injected in the edges of the wound at eight points in day 0 and day (Fig 2). Total injected cell number ranged from one million to 2 million cells. Cases were followed for 12 weeks for the change in ulcer size and the presence of any local reactions.
Fig 1: Microscopic Spindle shaped MSCs
Fig 2: Method of MSCs Injection
16 weeks
12 weeks
8 weeks
6 weeks
Conclusion
Local injection of autologous bone marrow derived mesenchymal stem cell is promising in healing of recalcitrant neuropathic diabetic foot ulcers. The procedure is safe and well tolerated by the patients. Optimum number of injected cells and frequency of injection is still to be determined
References
Katsilambros N, Dounis E, Makrilakis et al. (2010).Atlas of the diabetic foot. 2. Oxford: Wiley-Blackwell; ISBN:
Pradhan, L., C. Nabzdyk, et al. (2009). "Inflammation and neuropeptides: the connection in diabetic wound healing." Expert Rev Mol Med 11: e2.
Frykberg ,R. and Banks, J. (2015) . “Challenges in the Treatment of Chronic Wounds”. Adv Wound Care ; 4(9): 560–582.
Wu, Y., Wang, J., Scott, P.G., and Tredget, E.E. (2007). Bone marrow-derived stem cells in wound healing: a review. Wound Repair Regen; 15(Suppl. 1):S18–26
Key words : foot ulcers , chronic wounds, mesenchymal stem cells