CD4 CD25 FOXP3 regulatory T cells (Tregs) are involved in graft-specific tolerance after solid organ transplantation. However, adoptive transfer of polyspecific Tregs alone is insufficient to prevent graft rejection even in rodent models, indicating that graft-specific Tregs are required. We developed a highly specific chimeric antigen receptor that recognizes the HLA molecule A*02 (referred to as A2-CAR). Transduction into natural regulatory T cells (nTregs) changes the specificity of the nTregs without alteration of their regulatory phenotype and epigenetic stability. Activation of nTregs via the A2-CAR induced proliferation and enhanced the suppressor function of modified nTregs. Compared with nTregs, A2-CAR Tregs exhibited superior control of strong allospecific immune responses in vitro and in humanized mouse models. A2-CAR Tregs completely prevented rejection of allogeneic target cells and tissues in immune reconstituted humanized mice in the absence of any immunosuppression. Therefore, these modified cells have great potential for incorporation into clinical trials of Treg-supported weaning after allogeneic transplantation.
We conclude that spider silk is a viable guiding material for Schwann cell migration and proliferation as well as for axonal re-growth in a long-distance model for peripheral nerve regeneration.
Defects of peripheral nerves still represent a challenge for surgical nerve reconstruction. Recent studies concentrated on replacement by artificial nerve conduits from different synthetic or biological materials. In our study, we describe for the first time the use of spider silk fibres as a new material in nerve tissue engineering. Schwann cells (SC) were cultivated on spider silk fibres. Cells adhered quickly on the fibres compared to polydioxanone monofilaments (PDS). SC survival and proliferation was normal in Live/Dead assays. The silk fibres were ensheathed completely with cells. We developed composite nerve grafts of acellularized veins, spider silk fibres and SC diluted in matrigel. These artificial nerve grafts could be cultivated
in vitro
for one week. Histological analysis showed that the cells were vital and formed distinct columns along the silk fibres. In conclusion, our results show that artificial nerve grafts can be constructed successfully from spider silk, acellularized veins and SC mixed with matrigel.
The pathogenetic link between soft tissue trauma and the formation of posttraumatic lipomas is still controversially discussed. There are 2 potential explanations to correlate soft tissue trauma and adipose tissue tumor growth. The first is the formation of so-called posttraumatic pseudolipomas by prolapsing adipose tissue through fascia resulting from direct impact. A second possibility points toward lipoma formation as a result of preadipocyte differentiation and proliferation mediated by cytokine release following soft tissue trauma and hematoma formation.
Temporary arteriovenous loops provide adequate recipient vessels and flow to supply microvascular free flap tissue transfer in areas lacking recipient vessels and in which no other reconstructive options exists. No statistical differences in complications and overall outcome were found between immediate or secondary free tissue transfer. Meticulous monitoring of microvascular perfusion, however, is mandatory in both approaches and early intervention is necessary to ensure successful tissue transfer.
The aim of this study was to evaluate the relevant conditions for safe free flap transfers. The authors retrospectively studied the data from 150 patients who received free flaps at a single institution. Many parameters were analyzed to reveal if there was a correlation with respect to surgical or medical complications. Regarding safety of free tissue transfer, we found a worse prognosis in flaps where a revision of the microanastomosis had to be performed. Platelet count and leukocyte count had an impact on the prognosis. Patients older than 60 years did not have an increased rate of surgical complications. Apart from active osteomyelitis, the presence of comorbid conditions did not significantly impair the outcome of flap transfer, although smoking and diabetes correlated with minor surgical complications like wound breakdown or hematoma, respectively. Besides one case of lethal heart failure of an octogenarian patient, no severe medical complications occurred in this series of patients. Microvascular free tissue transfer is not significantly impaired by age and most comorbidities. Osteomyelitis as well as elevated leukocytes and lowered platelets may increase the complication rate and worsen the surgical prognosis. Smoking and diabetes might prolong the hospital course of the patients.
Background:Plastic and reconstructive surgeons are commonly faced with chronic ulcerations and consecutive wound infections of the feet as complications in patients with diabetes and/or peripheral arterial occlusive disease (PAOD). Microcirculatory changes seem to play an important role. However, the evaluation of functional changes in the soft tissue microcirculation at the plantar foot using combined Laser-Doppler and Photospectrometry System has not yet been performed in patients with DM or PAOD.Methods:A prospective, controlled cohort study was designed consisting of a total of 107 subjects allocated to 1 of 3 groups—group A: healthy subjects (57% males, 63.3 y); group B: patients with diabetes mellitus (DM) (53% males, 59.4 y); and group C: patients with PAOD (81% males, 66.1 y). Microcirculatory data were assessed using a combined Laser-Doppler and Photospectrometry System.Results:Global cutaneous oxygen saturation microcirculation at the plantar foot of healthy individuals was 8.4% higher than in patients with DM and 8.1% higher than in patients with PAOD (both P = 0.033). Patients with diabetes did not show significant differences in global cutaneous blood flow when compared with either healthy subjects or patients suffering from PAOD.Conclusions:Functional microcirculation at the plantar foot differs between healthy subjects and patients suffering from diabetes or PAOD of the same age. Patients with either diabetes or PAOD demonstrate deteriorated cutaneous oxygen saturation with equivalent blood perfusion at the plantar foot. More clinical studies have to be conducted to evaluate therapeutical methods that might ameliorate cutaneous oxygen saturation within diabetic foot disease and PAOD.
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