Autologous Bone Marrow-Derived Stem Cells for Chronic Wounds of the Lower Extremity: A Retrospective Study
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Stanley and Osler13 showed that a human venous leg ulcer with more than 15% of senescent cells would be more difficult to heal.
Application of stem cells in the bone marrow aspirate (BMA) locally to the wound bed has shown promising results for treating lower extremity ulcers. These stem cells are easily derived from the patient’s bone marrow, eliminating the risk of transmission of infectious disease transmission with allogeneic products. The aspirates contain two types of stem cells: hematopoietic and mesenchymal. The hematopoietic stem cells differentiate into red and white blood cells, platelets, and macrophages. The mesenchymal stem cells are multipotent and differentiate into multiple cell types involved in tissue repair when placed in the appropriate microenvironment.14
Bone marrow aspirates consist of inflammatory cell progenitors, which have been shown to participate in wound healing, mesenchymal stem cells, which appear to be phynotypically altered and/or senescent in chronic wounds, and multipotent stem cells.15–19 The progenitor cells show great potential in healing chronic wounds due to their unique immunologic properties and regenerative potential. However, questions still remain regarding the clinical mechanism of cell migration and proliferation, and of extracellular matrix deposition and remodeling after application of BMA-derived stem cells. The most significant problem with BMA use to date is the inability to quantify the number of viable stem cells once the BMA is extracted and immediately put on the wound. Cellular infiltration and regeneration in chronic wounds is poorly defined. Cellular senescence and the presence of biofilm in the wound bed are also important considerations, as they create barriers to healing in the chronic wound. When not adequately addressed, the latter factors are known to impede wound closure and may also prevent effective stem cell activity.
Current treatments and traditional approaches to wound closure, including thorough debridement, have had limited success and do not appear to have significantly decreased amputation rates in patients with underlying deficiency of required cellular activity. While debridement is successful in removing inhibitors and barriers to effective wound closure, including senescent cells, nonviable tissue, and bacteria harbored therein, it does not address the inability of cells in select populations to replicate.
This retrospective review was designed to help determine the potential efficacy and use of BMA-derived stem cells in chronic wounds of the lower extremity of multiple etiologies that had failed all other forms of treatment. The goal of the review was to determine if autologous bone marrow stem cell aspirate had the potential to assist non-healing lower extremity ulcers, which had been unresponsive to traditional methods by expediting wound closure and preventing further need for surgical intervention. The limitations, which are well recognized by the authors, are the relatively small population reviewed and etiology, as well as lack of randomization. However, the purpose of this review is similar to a Phase I trial in determining support for a concept versus demonstrating clinical efficacy. It is not the intent of the paper to discredit potential BMA use.
Materials and Methods
Patient selection. Patients were selected from the University of California San Diego (UCSD) Medical Center, Department of Surgery, Division of Trauma, by the senior authors without regard to race, gender, ethnicity, or economic status.