Therapeutic Potential in Wound Healing of Allogeneic Use of Equine Umbilical Cord Mesenchymal Stem Cells.

Wound healing after skin injury is a complex process, particularly in equines where leg wounds are prevalent and their repair is complicated due to the anatomical characteristics. Conventional treatments are not effective enough. The umbilical cord offers an unlimited source of adult mesenchymal stem cells (ucMSCs) from Wharton's jelly tissue. The present study aims to demonstrate the safety and therapeutic potential of the allogeneic use of equine ucMSCs (e-ucMSCs) in the healing of severe equine leg wounds. The methods employed were the isolation, culture and expansion of e-ucMSCs. Flow cytometry and a PCR assay were used for cell characterization. This study included an immunomodulation assay, a murine pre-clinical trial and the first phase of an equine clinical trial. Our results showed that e-ucMSCs express a functional HLA-G homolog, EQMHCB2. In the immunomodulation assay, the e-ucMSCs inhibited the proliferation of activated equine peripheral blood mononuclear cells (e-PBMCs). In the murine pre-clinical trial, e-ucMSCs reduced healing time by 50%. In the equine clinical trial, the injection of e-ucMSCs into severe leg lesions improved the closure time and quality of the tissues involved, regenerating them without fibrous tissue scar formation. In conclusion, the results of this study suggest that e-ucMSCs can be used allogeneically for wound healing by creating a tolerogenic environment.

Wound Healing by Allogeneic Transplantation of Specific Subpopulation From Human Umbilical Cord Mesenchymal Stem Cells.

In normal physiological conditions, restoration of a functional epidermal barrier is highly efficient; nevertheless, when it fails, one of the main consequences is a chronic ulcerative skin defect, one of the most frequently recognized complications of diabetes. Most of these chronic venous ulcers do not heal with conventional treatment, leading to the appearance of infections and complications in the patient. Treatments based on the use of autologous mesenchymal stem cells (MSC) have been successful; however, its implementation entails complications. The umbilical cord offers an unlimited source of adult MSC (ucMSC) from the Wharton's jelly tissue with the same relevant features for clinical applicability and avoiding difficulties. It has recently been characterized by one specific subpopulation derived from ucMSC, the differentiated mesenchymal cells (DMCs). This subpopulation expresses the human leukocyte antigen-G (HLA-G) molecule, a strong immunosuppressive checkpoint, and vascular endothelial growth factor (VEGF), the most potent angiogenic factor. Considering the importance of developing a more effective therapy for wound treatment, especially ulcerative skin lesions, we analyzed DMC safety, efficacy, and therapeutic potential. By immunohistochemistry, umbilical cords HLA-G and VEGF positive were selected. Flow cytometry revealed that 90% of the DMC subpopulation are HLA-G+, CD44+, CD73+, CD29+, CD105+, CD90+, and HLA-DR-. Reverse transcription-polymerase chain reaction revealed the expression of HLA-G in all of DMC subpopulations. Upon co-culture with the DMC, peripheral blood mononuclear cell proliferation was inhibited by 50%. In a xenograft transplantation assay, DMC improved wound healing with no signs of rejection of the transplanted cells in immunocompetent mice. This study confirms that HLA-G allows allogeneic cell transplantation, and VEGF is fundamental for the restoration of the failure in blood supply. DMC population has positive effects on wound healing by promoting local angiogenesis in skin lesions. DMC could play a very important role in regenerative medicine and could be a novel allogeneic cell-therapeutic tool for wound healing.

Anomalous intraosseous venous drainage: Bone perforators?

Objectives Anomalous intraosseous venous drainage is a rare and almost unknown entity; only 14 cases have been reported in the literature and 4 mentioned in textbooks. We report the characteristics of 35 further cases observed in 32 patients. Method After the presentation of two cases at the congress of the French Society of Phlebology in Paris (2013), 12 colleagues joined to present a large series of so-called bone perforators observed in their practice, all identified with at least a duplex investigation. Results Thirty-two patients suffering from varicose veins and/or skin changes (C2-C6) associated with a bone perforator of the tibia (with bilateral anomalies in three) are reported: 19 females and 13 males, average age 56.9. The majority of the affected legs were symptomatic (30/35). Bone perforator was an isolated finding in 27/35 legs. In three cases, the investigations revealed that the venous reflux in the bone originated from an incompetent posterior tibial vein. Conclusions We suggest the name of "bone perforators" for an anomalous tibial intraosseous venous drainage, feeding varicose veins, and in more advanced stages lipodermatosclerosis and leg ulcers. Most of them were successfully treated with surgery or sclerotherapy.

Tumor endovascular de Masson / Masson's intravascular tumor

Se analiza el caso de una paciente de sexo femenino, portadora de un tumor endovascular de Masson. Presentaba como antecedente un traumatismo de pelvis y el motivo de la consulta era várices y tumor en la región crural. Se hace hincapié en lo poco de ésta patología y en su origen en una vena, en tumores vasculares preexistentes o traumatismos. Se realizó su resección y el traumatismo de las várices. La evolución fue favorable, encontrándose libre de síntomas luego de 3 años de postoperatorio

Tumor endovascular de Masson / Massons intravascular tumor

Se analiza el caso de una paciente de sexo femenino, portadora de un tumor endovascular de Masson. Presentaba como antecedente un traumatismo de pelvis y el motivo de la consulta era várices y tumor en la región crural. Se hace hincapié en lo poco de ésta patología y en su origen en una vena, en tumores vasculares preexistentes o traumatismos. Se realizó su resección y el traumatismo de las várices. La evolución fue favorable, encontrándose libre de síntomas luego de 3 años de postoperatorio (AU)