There are only a few reports that describe the hepatocytic differentiation potential of human adipose tissue-derived mesenchymal stem cells (hADMSCs) and no reports that describe the in vivo functions of hepatocyte-like cells differentiated from somatic stem cells including hADMSCs. In this study, we established a new method for generation of functional hepatocyte-like cell clusters using floating culture method and induced functional hepatocyte-like cell clusters, which functioned effectively not only in vitro but also in vivo. The generated hepatocyte-like cell clusters were characterized by gene expression analysis, functional assays, and transplantation into non-obese diabetic severe combined immunodeficiency (NOD-SCID) mouse with chronic liver injury. The generated hepatocyte-like cell clusters expressed various genes normally found on mature hepatocytes. The cell clusters exhibited functional characteristics of hepatocytes: they expressed albumin, secreted urea, had cytochrome P450 activity, could take up low-density lipoprotein, and stored glycogen. Transplantation of these cell clusters into NOD-SCID mouse with chronic liver injury resulted in a significant improvement of serum albumin and total bilirubin levels. In summary, we established a new protocol for efficient induction of hADMSCs into functional hepatocyte-like cell clusters.
Whether or not multiple venous anastomoses reduce the risk of free-flap failure is a subject of controversy. We report here, for the first time, on the importance of selecting 2 separate venous systems of the flap for dual anastomoses. The efficacy of multiple anastomoses was verified through a retrospective review of 310 cases of the free radial forearm flap transfer. Dual anastomoses of separate venous systems (the superficial and the deep) showed a lower incidence of venous insufficiency than single anastomosis did (0.7% versus 7.5%; P < 0.05). On the other hand, dual anastomoses of a sole venous system showed no significant difference in the incidence of venous insufficiency compared with single anastomosis (11.5% versus 7.5%; P = 0.48). Our results suggest that dual venous anastomoses of separate venous systems is conducive to reduced risk of flap failure and affords protection against venous catastrophe through a self-compensating mechanism that obviates thrombosis of either anastomosis.
The combination surgery in Group C and simple posterior layer advancement of the LER in Group B provided complete surgical success. The present study suggests the importance of preoperative evaluation of horizontal laxity, allowing surgeons to perform the least amount of surgery to achieve success.
LN metastasis is regulated not only by the characteristics of cancer cells but also by microenvironmental factors of lymphatics and neutrophils, especially at the invasive front.
Adipose tissue is an attractive source for somatic stem cell therapy. Currently, human adipose tissue-derived stromal cells/mesenchymal stem cells (hADSCs/MSCs) are cultured with fetal bovine serum (FBS). Recently, however, not only human embryonic stem cell lines cultured on mouse feeder cells but also bone marrow-derived human MSCs cultured with FBS were reported to express N-glycolylneuraminic acid (Neu5Gc) xenoantigen. Human serum contains high titers of natural preformed antibodies against Neu5Gc. We studied the presence of Neu5Gc on hADSCs/MSCs cultured with FBS and human immune response mediated by Neu5Gc. Our data indicated that hADSCs/MSCs cultured with FBS expressed Neu5Gc and that human natural preformed antibodies could bind to hADSCs/MSCs. However, hADSCs/MSCs express complement regulatory proteins such as CD46, CD55, and CD59 and are largely resistant to complement-mediated cytotoxicity. hADSCs/MSCs cultured with FBS could be injured by antibody-dependent cell-mediated cytotoxicity mechanism. Further, human monocyte-derived macrophages could phagocytose hADSCs/MSCs cultured with FBS and this phagocytic activity was increased in the presence of human serum. Culturing hADSCs/MSCs with heat-inactivated human serum for a week could markedly reduce Neu5Gc on hADSCs/MSCs and prevent immune responses mediated by Neu5Gc, such as binding of human natural preformed antibodies, antibody-dependent cell-mediated cytotoxicity, and phagocytosis. Adipogenic and osteogenic differentiation potentials of hADSCs/MSCs cultured with heat-inactivated human serum were not less than that of those cultured with FBS. For stem cell therapies based on hADSCs/MSCs, hADSCs/MSCs that presented Neu5Gc on their cell surfaces after exposure to FBS should be cleaned up to be rescued from xenogeneic rejection.
Primary acquired NLDO patients exhibited the funnel type more frequently or there was a shorter distance from the entrance to the part with the shortest diameter than non-NLDO patients, which may enhance the risk of primary acquired NLDO.
The anatomy of the lateral canthus is analogous to that of the medial canthus, but with a less defined structure. Although the lateral canthal tendon occupies the major part of the lateral canthal anatomy, the lateral rectus capsulopalpebral fascia and other structures also play a significant role. Appropriate comprehension and consideration of the lateral canthal anatomy enable safe and effective performance in the lateral canthal surgeries. In this review, we present the lateral canthal anatomy along with updated topics. We discuss the lateral canthal tendon, lateral orbital thickening, lateral palpebral raphe, lateral canthal muscle, lateral rectus capsulopalpebral fascia, lateral check ligament, lateral retinaculum, and orbitomalar ligament.
Familial hypercholesterolemia (FH) is an autosomal codominant disease characterized by high concentrations of proatherogenic lipoproteins and premature atherosclerosis secondary to low-density lipoprotein (LDL) receptor deficiency. We examined a novel cell therapy strategy for the treatment of FH in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous FH. We delivered human adipose tissue-derived multilineage progenitor cells (hADMPCs) via portal vein and followed by immunosuppressive regimen to avoid xenogenic rejection. Transplantation of hADMPCs resulted in significant reductions in total cholesterol, and the reductions were observed within 4 weeks and maintained for 12 weeks. (125)I-LDL turnover study showed that the rate of LDL clearance was significantly higher in the WHHL rabbits with transplanted hADMPCs than those without transplanted. After transplantation hADMPCs were localized in the portal triad, subsequently integrated into the hepatic parenchyma. The integrated cells expressed human albumin, human alpha-1-antitrypsin, human Factor IX, human LDL receptors, and human bile salt export pump, indicating that the transplanted hADMPCs resided, survived, and showed hepatocytic differentiation in vivo and lowered serum cholesterol in the WHHL rabbits. These results suggested that hADMPC transplantation could correct the metabolic defects and be a novel therapy for inherited liver diseases.
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