A. Cagri Uysal

Concise Review: Adipose‐Derived Stem Cells as a Novel Tool for Future Regenerative Medicine

The potential use of stem cell‐based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in the genetic manipulation of human ESCs, even though these cells are, theoretically, highly beneficial. Mesenchymal stem cells seem to be an ideal population of stem cells for practical regenerative medicine, because they are not subjected to the same restrictions. In particular, large number of adipose‐derived stem cells (ASCs) can be easily harvested from adipose tissue. Furthermore, recent basic research and preclinical studies have revealed that the use of ASCs in regenerative medicine is not limited to mesodermal tissue but extends to both ectodermal and endodermal tissues and organs, although ASCs originate from mesodermal lineages. Based on this background knowledge, the primary purpose of this concise review is to summarize and describe the underlying biology of ASCs and their proliferation and differentiation capacities, together with current preclinical and clinical data from a variety of medical fields regarding the use of ASCs in regenerative medicine. In addition, future directions for ASCs in terms of cell‐based therapies and regenerative medicine are discussed. STEM CELLS 2012;30:804–810

The Effect of Adipose-Derived Stem Cells on Ischemia-Reperfusion Injury: Immunohistochemical and Ultrastructural Evaluation

Background: Advances in the treatment of reperfusion injury have created an opportunity for plastic surgeons to apply these treatments to flaps and implanted tissues. The authors examined the direct and indirect effects of adipose-derived stem cells on ischemia-reperfusion injury on a skin flap model to determine the in vivo differentiation of adipose-derived stem cells to endothelial cells; the levels of vascular endothelial growth factor (VEGF), transforming growth factor-&bgr;, and fibroblast growth factor; and the ultrastructural changes apparent with scanning electron microscopy to clarify the initial events and the following cascades. Methods: Two identical cranial based random flaps with a dimension of 1 × 5 cm were elevated on the dorsums of 20 ICR mice. The left flap was designated as the control and the right flap was injected with adipose-derived stem cells. The flaps were then subjected to 6 hours of ischemia by clamping the pedicle, and then reperfusion. Results: The mean viable flap length in the control and experimental groups was 15.2 ± 3.4 mm and 24.4 ± 2.9 mm, respectively. The mean viable flap area in the control and experimental groups was 12.9 ± 4.1 mm2 and 21.8 ± 3.7 mm2, respectively. The in vivo differentiation of adipose-derived stem cells to endothelial cells was observed. The immunohistochemical stainings, VEGF, transforming growth factor-&bgr;, and fibroblast growth factor revealed increased levels in the experimental groups. Scanning electron microscopy indicated mild injury in the experimental group. Conclusions: The adipose-derived stem cells could prevent ischemia-reperfusion injury, mainly by regulating the growth factors. Although VEGF was the foremost inhibitor of injury, the overall cascade was enhanced by adipose-derived stem cells, with the help of the other growth factors.

An Alternative Dressing Material for the Split-thickness Skin Graft Donor Site: Oxidized Regenerated Cellulose

The split-thickness skin graft (STSG) donor sites have been treated with various and plenty of dressing techniques and materials. An ideal STSG donor site dressing should have antibacterial, hemostatic, and promoting epidermal healing properties. We have performed a prospective study to evaluate the effect of the oxidized regenerated cellulose on STSG donor site healing. Between January 2002 and January 2005, 40 patients who were operated in any kind of reconstructive operations with STSG donor sites were included in the study. One half of the wound was covered with oxidized regenerated cellulose and the other half of the same wound of the same patient was covered with fine mesh gauze treated with Furacin (nitrofurazone). The patients were grouped into 2 depending on the dressing technique: group I, semiclosed and group II, closed. The wounds were evaluated for healing time, infection, pain perception of the patient, and final esthetic results. The oxidized regenerated cellulose side of the group I was healed in a mean of 6.5 ± 0.51 days; in group II, 5.4 ± 0.50 days (range, 5–6 days). The fine mesh gauze treated with Furacin in group I was healed in a mean of 9.9 ± 0.97 days (range, 8–11 days); in group II, 8.4 ± 0.99 days (range, 7–10 days). There was a statistical significance between the oxidized regenerated cellulose side and the fine mesh gauze side (P < 0.001) in group I and group II separately. The difference between group I and group II was statistically significant in the oxidized regenerated cellulose side (P < 0.001), and the difference between group I and group II was statistically significant in the fine mesh gauze side (P < 0.005). The antibacterial, hemostatic, and absorbable property of the oxidized regenerated cellulose could ensure the utilization as an alternative STSG donor site dressing, especially because the positive influence over the wound healing was proven.

Differentiation of Adipose-Derived Stem Cells for Tendon Repair

The goal of primary tendon repair is to increase tensile strength at the time of mobilization. Tendon repair and regeneration using mesenchymal stem cells have been described in several studies; however, the use of adipose derived stem cells (ASCs) for tendon repair has only recently been considered. In order to establish a suitable experimental model for the primary tendon repair using ASCs, this chapter describes the detailed methods for: (1) isolating stem cells from adipose tissue, (2) generation of a primary tendon injury and repair model, (3) evaluating functional restoration by measuring tensile strength, and (4) investigating the mechanisms involved in ASC-mediated tendon healing by histological and immunohistochemical analyses. Topical administration of ASCs to the site of injury accelerates tendon repair, as exhibited by a significant increase in tensile strength, direct differentiation of ASCs toward tenocytes and endothelial cells, and increases in angiogenic growth factors. These findings suggest that ASCs may have a positive effect on primary tendon repair and may be useful for future cell-based therapy.

Prefabrication of tissue engineered bone grafts: an experimental study.

The purpose of this study was to determine whether angiogenesis could successfully be induced into bone tissue that was engineered by cultured adipose-derived stem cells with porous beta-tricalcium phosphate and whether its biologic properties could be maintained by flap prefabrication technique.Adipose-derived stem cells with porous beta-tricalcium phosphate were implanted into the superficial inferior epigastric artery flap of the Fisher rats. After prefabrication for 8 weeks, the prefabricated flaps were elevated and the pedicles were clamped for 4 hours. The samples were harvested after 2 weeks for analyses.Angiogenesis was significantly increased in the prefabricated groups (P < 0.05). There was no significant difference between the prefabricated and nonprefabricated groups in terms of the osteogenic capacity (P > 0.5).The promising results obtained with prefabrication in tissue engineered bone grafts encourage the clinical application of this technology. Thus, prefabrication may be a useful technique in any engineered bone tissue transfer.

Adipose-Derived Stem Cells as a Novel Tool for Future Regenerative Medicine

Stem cell-based therapies for the repair and regeneration of damaged tissues and organs offer a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells or induced pluripotent stem cells in clinical situations may be still limited due to cell behaviors, ethical considerations, and genetic manipulation, even though these cells are theoretically highly beneficial. Adipose-derived stem cells (ASCs) seem to be an ideal population of stem cells for practical regenerative medicine since they are plentiful, of autologous tissue origin and thus non-immunogenic, and are more available due to minimal ethical considerations. Furthermore, recent basic research and preclinical studies have revealed that the use of ASCs in regenerative medicine is not limited to mesodermal components, but extends to both ectodermal and endodermal tissues and organs, even though ASCs are mesodermal in origin. This chapter will describe the biology of ASCs and their proliferation and differentiation capacities, and will summarize the current preclinical and clinical data from a variety of medical fields on the use of ASCs in regenerative medicine.

Staged and late-period reconstruction of the crushed hand: prefabricated osseous flap.

The principle of controlled utilization of increased vascularity in the regions of artificially established ischemia constituted the basis of prefabrication of the vascular induction through staged transfers. We have used this principle, and a part of a metacarpal bone was prefabricated with an artery. The artery was inserted into the bone, and a defect was repaired with this prefabricated osseous flap; meanwhile, another defect was amended with a bone graft. The static bone scintigraphy of the hand at the 6-month postoperative stage indicated evident superiority of the vascularity of the prefabricated osseous flap at the ring finger when compared with the bone graft at the middle finger. The angiography demonstrated a high vascular pattern of the flap at its location at the proximal phalanx of the ring finger. The structures that remained healthy after the injury either on the amputated side or on the hand could be used in reconstruction. The tendinous and osseous structures could be used as free grafts, and the vascular structures could be transferred as vascular pedicles, allowing the creation of previously nonexistent flaps and composite tissues that were ideal for reconstruction. Any tissue possessing a vascular supply could be used as a vascular crane in any prefabrication process.

Squamous Cell Carcinoma of the Auricle Arising from Keloid after Radium Neddle Therapy

The squamous cell carcinoma (SCC) of the auricle was one of the common tumors of not only skin but also ear. SCC of the auricle was described to be the carcinoma of old age with some predisposing factors and keloid was known to be one of the predisposing factors for malignant tumors. Keloid and radium needle therapy were risk factors, latter the major, independently from each other and were reported to conclude in SCC depending on the duration for the keloid and the dose for the radium needle therapy. The increased age with the long duration of these predisposing factors should have to be kept in mind in every situation when these treatment modalities had been planned to. Surgical interventions should always be the first choice in the treatment of not only the carcinomas but also in keloids in selected cases.

Periodontal Tissue Regeneration with Adipose-Derived Stem Cells

The invention is a microcomponent sheet architecture wherein macroscale unit processes are performed by microscale components. The sheet architecture may be a single laminate with a plurality of separate microcomponent sections or the sheet architecture may be a plurality of laminates with one or more microcomponent sections on each laminate. Each microcomponent or plurality of like microcomponents perform at least one chemical process unit operation. A first laminate having a plurality of like first microcomponents is combined with at least a second laminate having a plurality of like second microcomponents thereby combining at least two unit operations to achieve a system operation.