SLR - November 2020 - Deep N. Shah

Autologous Nanofat Transplantation Accelerates Foot Wound Healing in Diabetic Rats

Reference: Chen L, Wang ZC, Ma JJ, et al. Autologous Nanofat Transplantation Accelerates Foot Wound Healing in Diabetic Rats. Regen Med. 2019;14(3):231-241. doi:10.2217/rme-2018-0169

Scientific Literature Review

Reviewed By: Deep N. Shah, DPM
Residency Program: Crozer Keystone Health System – Chester, PA

Podiatric Relevance: By 2040, approximately 642 million people between age of 20 and 79 are expected to suffer from Diabetes Mellitus. Diabetic foot syndrome is one of the most common complications in diabetic patients. The combination of nerve, microvasculature lesions, infections and pedal deformity often contributes to limb ischemia, and amputations. Increase in popularity, with growing number of animal experiments, abundant donor sites availability, and minimal complications have proved the effectiveness of stem cells in the treatment of ischemic diseases. Nanofat consisting of Adipose-derived stem cells (ADSCs), cytokines, growth factors and extracellular matrix (ECM) are capable of effectively promoting wound epithelization and the formation of microvascular frameworks by differentiating into vascular endothelial cells, and secreting various cytokines. As a result, authors speculated that nanofat may have positive effect on diabetic foot wounds. 

Methods: Emulsified and filtered nanofat was transplanted into 5 millimeters full thickness cutaneous left foot wound of 6 diabetic rats (EG). Phosphate-buffered saline (PBS) injection in the right served as control group (CG). Authors measured wound size, the extent of epithelization, micro vessel density, and the expression levels of cytokines at six different times point (day 2,4,7,9,11,14) post operatively. 

Results: The bodyweight, fasting blood glucose of experimented (EG) rats was significantly higher than that of control (CG) rats after four weeks on different diets. Flow cytometry analysis of four rat nanofat samples revealed that ADSCs (marked with CD45-/CD31-/CD90+) accounted for 17.07 ± 2.22 percent of all viable cells in nanofat. Healing of diabetic foot wounds was more rapid in the nanofat-treated group, which had a wound area of 25.7 ± 2 percent of the original area on day seven and 8.4±1.1 percent on day nine, than in the PBS-treated feet, which had areas of 40.5 ± 1.9 percent  and 35.5 ± 2.2 percent of the original areas at the same time points. However, wounds treated with nanofat healed completely by day 14 (0.0 percent), whereas wounds treated with PBS remained unhealed (2.6 ± 1.5 percent). Additionally, H&E staining confirmed the inadequate re-epithelialization of wounds in the PBS-treated feet compared with the nearly complete re-epithelialization in the nanofat-treated feet at day 14. Also, higher expression levels of cytokines, and growth factors (MCP-1 and VEGF) were noted in the nanofat-treated group. 

Conclusions: Diabetes Mellitus (DM) is a worldwide health threat. Complex pathogenesis of diabetes often damages nerves, vessels, immune system often creating pedal ulcerations. Dynamic and synchronized process involving inflammation, proliferation, differentiation, angiogenesis, re-epithelization, and remodeling are often require healing complex wounds by any means necessary. Although, limited research has been published regarding implantation of nanofat to treat chronic diabetic wounds, autologous nanofat consisting of ECM, ADSC, cytokines, and growth factors (I.e., VEGF) have shown significant differences in wound healing at days seven and nine testing. In vivo experiments to explore the role of regeneration and repair function of nanofat in wound healing. The results showed that nanofat can promote wound healing in diabetic rats, which provides an animal experimental basis for further clinical research on the role of nanofat in diabetic foot ulcers healing.  

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