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Given the non-healing nature of these wounds, other products or procedures were utilized after 6 weeks to augment the healing process when no improvement or deterioration was seen. At 6, 11, and 18 weeks after the application of BMA, two patients received living skin substitutes since the wounds appeared to have little to no intrinsic cell activity. Although there is strong evidence that mesenchymal stem cells can assist in wound healing, there are insufficient human studies with an adequate number of subjects to prove its validity and efficacy.
  The largest study to date using bone marrow-derived mesenchymal stem cells with or without autologous skin graft was published by Yoshikawa et al²⁵ in 2008. This study included 20 subjects with various nonhealing wounds. The authors reported complete healing in 18 patients and showed regeneration of native tissue by histologic examination. The study supported previous literature that bone marrow-derived stem cells are associated with dermal rebuilding, remodeling, increase in wound vascularity, and reduced fibrosis.²⁵
  Falanga et al²⁶ applied up to three applications of autologous culture-expanded mesenchymal stem cells with a fibrin glue system to acute wounds and chronic wounds. The acute wounds secondary to excision of non-melanoma skin cancers healed within 8 weeks. The chronic, year-long lower extremity wounds significantly decreased or healed in 16 to 20 weeks; however, this healing time does not appear to offer an advantage over healing times of other treatments published in the literature. This study showed a strong correlation between the number of mesenchymal stem cells per square centimeter surface area and reduction in ulcer size. The fibrin glue potentially keeps stem cells in the wound base and migrates out gradually as healing progresses.²⁶ Injection of fibrin glue with adipose tissue-derived mesenchymal stem cells into the fistula tract in 25 patients showed healing rate of 71% with recurrence rate of 17.6%.²⁷
  The present results suggest that fresh autologous bone marrow aspirate applied topically may help stimulate healing, but may not necessary lead to a significant visible decrease in wound closure within a given time frame compared to other treatment modalities that are currently approved and available on the US and global markets.

Conclusion

  The authors are acutely aware of the many limitations of this review. The purpose of this small retrospective study was to examine a technique for stem cell extraction and determine any proof of concept. We acknowledge that this was not possible, as the patients who had complete documentation and follow up were very limited. Furthermore, as the treated patients were not part of any on-going trial at the time of treatment, two different xenograft products were used. Ulcer etiologies and patient medical histories were also not demographically equal, which makes drawing any conclusions from the results difficult. Two different types of xenograft were used. The two products differ in characteristics, which could have had varying effects on outcomes, as non-cross linked products tend to rapidly degenerate and may be less effective in wounds with high levels of inflammatory enzymes. We do believe that the review provides the reader with information on a new technique that warrants further investigation in a larger randomized controlled trial with demographically equal patients with the same wound etiology. We hope to initiate such a study in the near future. Published data on xenografts alone have suggested that correctly applied, flexible cross-linked xenografts are ideal for problematic wounds, even without stem cells, to help close complex wounds.

References

1. Bern H, Sheehan P, Boulton AJ. Protocol for treatment of diabetic foot ulcer. Am J Surg. 2004;187:1S–10S.

2. Phillips TJ.