Shuzhong Guo

Human facial allotransplantation: a 2-year follow-up study.

BACKGROUND Progress in composite tissue allotransplantation could provide a new treatment for patients with severe facial disfigurements. We did a partial facial allotransplantation in 2006, and report here the 2 year follow-up of the patient. METHODS The recipient, a 30-year-old man from China, had his face severely injured by a bear in October, 2004. Allograft composite tissue transplantation was done in April, 2006, after careful systemic preparation. The surgery included anastomosis of the right mandibular artery and anterior facial vein, whole repair of total nose, upper lip, parotid gland, front wall of the maxillary sinus, part of the infraorbital wall, and zygomatic bone. Facial nerve anastomosis was done during the surgery. Quadruple immunomodulatory therapy was used, containing tacrolimus, mycophenolate mofetil, corticosteroids, and humanised IL-2 receptor monoclonal antibody. Follow-up included T lymphocyte subgroups in peripheral blood, pathological and immunohistochemical examinations, functional progress, and psychological support. FINDINGS Composite tissue flap survived well. There were three acute rejection episodes at 3, 5, and 17 months after transplantation, but these were controlled by adjustment of the tacrolimus dose or the application of methylprednisolone pulse therapy. Hepatic and renal functions were normal, and there was no infection. The patient developed hyperglycaemia on day 3 after transplantation, which was controlled by medication. INTERPRETATION Facial transplantation could be successful in the short term, but the procedure was not without complications. However, promising results could mean that this procedure might be an option for long-term restoration of severe facial disfigurement.

Mesenchymal Stem Cells Enhance the Induction of Mixed Chimerism and Tolerance to Rat Hind-Limb Allografts after Bone Marrow Transplantation

BACKGROUND Mixed hematopoietic chimerism via bone marrow transplantation has been shown to induce donor specific tolerance to solid organ allografts, but graft versus host disease (GVHD) remains to be a risk. Composite tissue allografts may need a higher percentage of donor chimerism compared with less immunogenic solid organ allografts. In this study, we investigated the potential of mesenchymal stem cells (MSCs) in the induction of stable and high level chimerism and subsequent donor-specific tolerance to composite tissue allograft without the incidence of graft versus host disease (GVHD). METHODS Fully mismatched, 4- to 8-wk-old Brown Norway (RT1(n)) and Lewis (RT1(1)) rats were used as cell or hind-limb donors and recipients, respectively. Recipients received a conditioning regimen consisting of antilymphocyte serum, standard immunosuppressive therapy (rapamycin: 0.2 mg/kg/d; days 0 approximately 130) and 3 Gy total body irradiation, followed by an intraportal co-infusion of allogeneic MSCs and bone marrow cells (day 0); then performing hind-limb allotransplants (30 d after BMT); 100 d after hind-limb transplantations, immunosuppressive therapy was stopped and to observe the survival time of the hind-limb allografts. RESULTS When co-infusion of allogeneic MSCs was administered, 14/15 recipients developed stable and high level chimerism. Subsequently, in the donor specific group, the survival time of hind-limb allografts without RAPA were remarkably prolonged compared with other groups. The results of the histopathological evaluation of skin biopsy and mixed lymphocyte cultures confirmed this operational donor specific tolerance. Without MSCs, only 2/7 of the recipients developed stable chimerism, but GVHD occurred in both of them, and the level of the chimerism was much lower. On the other hand, GVHD was not observed in any of the recipients infused with MSCs (0/15). CONCLUSION This study indicates a potential use of MSCs for induction of stable and high level mixed hematopoietic chimerism and subsequent donor specific tolerance in clinical composite tissue allotransplantation.

Trichostatin A inhibits collagen synthesis and induces apoptosis in keloid fibroblasts

Keloid, a fibro-proliferative benign tumor of skin, is characterized by an enriched milieu of growth factors and an abundant accumulation of extracellular matrix (ECM). Transforming growth factor (TGF)-β1 is well known as the crucial fibrogenic cytokine promoting ECM production and tissue fibrosis in keloid forming. Epigenetic modifications have been shown to play a role in the pathogenesis of cancer as well as autoimmune and inflammatory disorders. Recent publication reports epigenetic modifications in keloid fibroblasts that include an altered pattern of DNA methylation and histone acetylation. Therefore, the field of epigenetics may provide a new therapeutic idea for keloid treatment strategies. Currently, there is some evidence from experimental studies that histone deacetylase (HDAC) inhibitor Trichostatin A (TSA) causes abrogation of TGF-β1 induced collagen synthesis in skin fibroblasts. Furthermore, TSA could suppress proliferation and induce apoptosis in a broad spectrum of tumor cells both in vitro and in vivo. These findings suggest that TSA could also cause abrogation of TGF-β1 induced collagen synthesis and induce apoptosis of proliferating keloid fibroblasts.

Troglitazone suppresses transforming growth factor-β1-induced collagen type I expression in keloid fibroblasts

Background  Peroxisome proliferator‐activated receptor (PPAR)‐γ agonists are increasingly used in patients with diabetes and some studies have suggested a beneficial effect on organ fibrosis. However their effects on dermal fibrosis in keloids are unknown.

An anatomical study with clinical application of one branch of the supraclavicular artery.

The supraclavicular flap is an important method for the reconstruction of the neck. In this study, the authors attempted to clarify the mechanism of blood flow into the supraclavicular flap based on the thoracic branch of the supraclavicular artery. Additionally, the authors discuss the clinical application of such anatomy. Thirty fresh cadavers and 13 preserved cadavers were dissected to observe the anatomic features of the pectorally extended supraclavicular flap. Additionally, 46 clinical cases were treated with such a flap. We identified two branches of the supraclavicular artery. A deltoid branch that extended to the acromial region and a thoracic branch that traveled to the anterior thoracic region. Using these data, all such flaps operated by us have to date, survived with satisfactory results. The pectorally extended supraclavicular flap could be used to repair defects on the ipsilateral or contralateral face, neck, and anterior thorax. Clin. Anat. 22:215–220, 2009.

Observations on the survival and neovascularization of fat grafts interchanged between C57BL/6-gfp and C57BL/6 mice.

Background: Autologous fat transplantation has become a prevalent option for soft-tissue augmentation throughout the body. However, there is still much controversy over whether the fat grafts have survived or have been replaced in the recipient sites and over how the vessels grow. Methods: After C57BL/6-gfp mice and C57BL/6 mice were paired randomly, the inguinal fat was excised and cut into pieces with scissors, and the adipose granules, approximately 0.2 ml (0.195 g), were transplanted subcutaneously with syringes to the dorsa of the paired mice. Samples were obtained at different time intervals: 3 days, 7 days, 2 weeks, 4 weeks, 2 months, 3 months, and 4 months after transplantation. Each fat sample was weighed to evaluate the graft volume. Histology, origin, and densities of neovascularization were examined by immunohistochemical staining. Results: At 4 months, there was no significant difference in either graft survival or histologic evaluation. Histologic evaluation manifested the normal physiologic process of inflammation, neovascularization, remodeling, and maturity at different time intervals. At the endpoint, the immunohistochemical staining of CD34 showed that the difference in capillary density of the fat graft—31.3 ± 3.9 capillaries/mm2 on the dorsa of the C57BL/6-gfp mice and 29.6 ± 3.2 capillaries/mm2 on the dorsa of the C57BL/6 mice—was not statistically significant. The &agr;-smooth muscle actin staining indicated that there were neovascularized vessels in both C57BL/6-gfp and C57BL/6 fat grafts. Conclusions: Fat grafts can survive and neovascularized vessels can grow from the recipient sites. Fat transplantation is feasible and will be applied more widely if fat graft survival is improved.

The association of functional polymorphisms in the aryl hydrocarbon receptor (AHR) gene with the risk of vitiligo in Han Chinese populations.

Background  Vitiligo is an acquired depigmentation disorder resulting from selective destruction of melanocytes. The aryl hydrocarbon receptor (AHR) is vital to the regulation of melanogenesis and melanocyte proliferation and differentiation through modulating the expressions of melanogenesis‐related genes. AHR mutations may negatively affect AHR proteins and its target genes. Therefore, we hypothesized that AHR polymorphisms might be involved in vitiligo by impacting the transcriptional activities of related genes as mentioned above.

Possibilities and potential roles of estrogen in the pathogenesis of proliferation hemangiomas formation

Hemangiomas, often categorized as angiogenic diseases, are the most common tumors of infancy, the life span of which is generally divided into proliferating phase, involuting phase, and involuted phase. Despite their high prevalence, the mechanism leading to proliferation hemangiomas formation is poorly understood and the best approach to their management remains controversial. None of the current therapeutic modalities is ideal, partly because the pathogenesis of hemangioma and the mechanism of its proliferation are far from clear. Many clues reveal that estrogen has an important role in developing the vascular system, experimental and clinical evidences accumulated in recent years also suggest the potential for estrogen to influence neovascularization. Based on those, we hypothesize that estrogen play a potential role in the development of hemangiomas, mainly by regulating some key angiogenic factors, including MMP-9, EPCs, VEGF, NO, etc. Accepting the hypothesis to be correct, a therapy that identify estrogen as a potential target for the design of new, more specific treatments can be used to prevent the proliferation hemangiomas formation. The hypothesis may lead a new direction in the study of mechanisms for proliferation hemangiomas formation, and further study of the precise mechanisms for estrogen-induced hemangiomas will produce effective antiestrogens and estrogen receptor antagonists as new medication for the very difficult problem.

Repair of faciocervical scars by expanded deltopectoral flap.

Objective:To explore the approach to repair faciocervical scars. Methods:Eighty-six patients with large faciocervical scars were repaired using the expanded deltopectoral flaps. After expansion, the flaps were transpositioned to repair faciocervical scars. Three weeks later the pedicles were separated and their skin tubes were flattened for the repair of the remaining faciocervical scars. Results:Of the 86 cases, 80 achieved effective results with all the flaps surviving. Six cases showed achromatosis after healing because of the compromised blood supply. Conclusion:The application of expanded deltopectoral flaps is proved to be an effective way of repairing faciocervical scars. The flaps are as thin as those subdermal vascular network flaps’, so when transferred to the facial region, the flaps will not swell and can well match with their peripheral tissues.

Enhancement of fat graft survival by bone marrow-derived mesenchymal stem cell therapy.

Background: Adipose-derived stem cells can improve fat graft survival, but there is no literature reporting whether bone marrow–derived mesenchymal stem cells enhance fat graft survival. The authors explored the feasibility of enhancing fat graft survival using bone marrow–derived mesenchymal stem cells. Methods: Third-passage expanded rabbit bone marrow–derived mesenchymal stem cells were characterized by adipocyte and osteocyte differentiation and by CD29 and CD31 expression. Three were three groups of nude mice in this experiment: group A, mesenchymal stem cells; group B, expanded mesenchymal stem cells; group C, Dulbeccos medium as a blank control. The transplanted mixture contained 0.3 ml of adipose granule and 0.2 ml of cell components of 5 × 106 cells. Four months later, grafts were harvested, weighed, and analyzed. Results: Expanded cells were successfully isolated and identified by fibroblast-like adherent shape and osteogenic and adipogenic differentiation. The results were 24.6 ± 3.4 percent for CD29 and 1.8 ± 0.4 percent for CD31 in group A, and 45.0 ± 4.9 percent for CD29 and 1.6 ± 0.3 percent for CD31 in group B. Fat graft survival rates were 0.2052 ± 0.0015 g, 0.1761 ± 0.0014 g, and 0.1350 ± 0.0020 g in groups A, B, and C, respectively (p < 0.05). Fat grafts in group A exhibited the best survival and morphologic integrity, uniform lipid droplets, and rich blood vessels; those in group B exhibited modest survival, less integrity, less uniform lipid droplets, and connective tissue septa; and those in group C exhibited some large bubbles, varied sizes of lipid droplets, and significant fibrous septa (p < 0.05). The vascular densities for groups A, B, and C were 30.4 ± 1.5, 27.2 ± 1.3, and 23.3 ± 1.9 capillaries/mm2, respectively (p < 0.05). Conclusions: Bone marrow–derived mesenchymal stem cells and expanded bone marrow–derived mesenchymal stem cells are capable of improving fat graft survival; bone marrow–derived mesenchymal stem cells are more potent than expanded bone marrow–derived mesenchymal stem cells for doing so.