If you’ve ever seen the lesser-known Sam Raimi movie Darkman, you probably remember that the plot involved the main character, Dr. Westlake, trying to figure out a way to “print” liquid skin to help burn victims. Westlake never did figure out how to keep the synthetic skin from destabilizing past the 98 minute mark, but luckily, Wake Forest Instititute for Regenerative Medicine researchers seem to have mastered it, showing off their amazing skin printer that uses living cells instead of ink.
As the researcher note, “any loss of full-thickness skin of more than 4 cm in diameter will not heal by itself.” Enter their device, which allows a modified inkjet printer to produce reams of fresh skin which can be used to patch up victims of skin trauma. They’ve already tested it on mice, with extremely positive results.
How does the printer work? It has two heads: one dispenses skin cells mixed with a blood coagulent and type I collagen, and the other pumps out thrombin, which is another coagulate. Sprayed together, these chemicals create a reaction and form fibrin, which again helps to clot blood. On top of that, the printer then adds a layer of outer surface skin. Voila!
There’s still testing to be done — the next stage is on pigs, then human trials — but so far, this looks promising… if not to replace burned off skin, then at least to print out some life-like Halloween masks.
Wednesday
Von Willebrand factor and thrombin activation in children with newly diagnosed acute lymphoblastic leukemia: An impact of peripheral blasts†
Abstract
Background
The pathogenesis and the impact of therapy on thrombin activation in children with acute lymphoblastic leukemia (ALL) are unknown. Steroids may contribute to ALL-associated thrombosis. We explored the hemostatic effects of methylprednisolone monotherapy (MpMT) (32 mg/m2/day IV × 3 days) in children with newly diagnosed ALL.
Methods
Children (>1 to ≤18 years of age) enrolled on DFCI ALL05-01 protocol (n = 30; mean age 6.3 years), without prior steroid therapy, were eligible for study. Overnight fasting pre- and post-MpMT samples were analyzed for coagulation factors [FVIII:C, von Willebrand factor antigen (vWF:Ag) and fibrinogen] and parameters of thrombin generation [prothrombin fragments 1.2 (F1.2), thrombin–antithrombin complex (TAT), and D-dimer].
Results
At diagnosis F1.2 (1.5 nmol/L), TAT (10.9 µg/L), and D-dimers (2,766 ng/ml) levels were increased indicating endogenous thrombin activation. Patients with peripheral blasts (n = 17) had higher levels of vWF:Ag (1.89 vs. 1.14 P = 0.001), TAT (15.39 vs. 5.02 P = 0.038), and D-dimer (3,640 vs. 1,623 P = 0.019) compared to those without peripheral blasts. Following MpMT the blast count decreased significantly from 24% to 3.5% (P < 0.001) with reduction in level of vWF:Ag (1.5, P < 0.01), TAT (8.9, P = 0.42), and D-dimer (P = 0.018) despite 30% increase in FVIII:C levels (P = 0.005). However, patients without peripheral blasts had no significant change in vWF:Ag levels (1.14 vs. 1.25; P = 0.142) and had an increase in thrombin generation parameters.
Conclusions
We postulate that peripheral blasts through endothelial activation stimulate vWF:Ag production/secretion causing coagulation activation. Methylprednisolone therapy reduces the blast count and indirectly suppresses the coagulation activation. Future studies are required to confirm these findings. Pediatr Blood Cancer 2010;54:963–969
Uma Athale MD, MSc1,2,*, Albert Moghrabi MD3, Trishana Nayiager BScH, CCRP2, Yves-Line Delva RN3, Lehana Thabane PhD4,5,6, Anthony K.C. Chan MBBS1,2
Pediatric Blood & Cancer
Volume 54, Issue 7, pages 963–969, 1 July 2010
Background
The pathogenesis and the impact of therapy on thrombin activation in children with acute lymphoblastic leukemia (ALL) are unknown. Steroids may contribute to ALL-associated thrombosis. We explored the hemostatic effects of methylprednisolone monotherapy (MpMT) (32 mg/m2/day IV × 3 days) in children with newly diagnosed ALL.
Methods
Children (>1 to ≤18 years of age) enrolled on DFCI ALL05-01 protocol (n = 30; mean age 6.3 years), without prior steroid therapy, were eligible for study. Overnight fasting pre- and post-MpMT samples were analyzed for coagulation factors [FVIII:C, von Willebrand factor antigen (vWF:Ag) and fibrinogen] and parameters of thrombin generation [prothrombin fragments 1.2 (F1.2), thrombin–antithrombin complex (TAT), and D-dimer].
Results
At diagnosis F1.2 (1.5 nmol/L), TAT (10.9 µg/L), and D-dimers (2,766 ng/ml) levels were increased indicating endogenous thrombin activation. Patients with peripheral blasts (n = 17) had higher levels of vWF:Ag (1.89 vs. 1.14 P = 0.001), TAT (15.39 vs. 5.02 P = 0.038), and D-dimer (3,640 vs. 1,623 P = 0.019) compared to those without peripheral blasts. Following MpMT the blast count decreased significantly from 24% to 3.5% (P < 0.001) with reduction in level of vWF:Ag (1.5, P < 0.01), TAT (8.9, P = 0.42), and D-dimer (P = 0.018) despite 30% increase in FVIII:C levels (P = 0.005). However, patients without peripheral blasts had no significant change in vWF:Ag levels (1.14 vs. 1.25; P = 0.142) and had an increase in thrombin generation parameters.
Conclusions
We postulate that peripheral blasts through endothelial activation stimulate vWF:Ag production/secretion causing coagulation activation. Methylprednisolone therapy reduces the blast count and indirectly suppresses the coagulation activation. Future studies are required to confirm these findings. Pediatr Blood Cancer 2010;54:963–969
Uma Athale MD, MSc1,2,*, Albert Moghrabi MD3, Trishana Nayiager BScH, CCRP2, Yves-Line Delva RN3, Lehana Thabane PhD4,5,6, Anthony K.C. Chan MBBS1,2
Pediatric Blood & Cancer
Volume 54, Issue 7, pages 963–969, 1 July 2010
Thursday
Bone marrow-derived progenitor cells prevent thrombin-induced increase in lung vascular permeability
Am J Physiol Lung Cell Mol Physiol 298: L36-L44, 2010
Since thrombin activation of endothelial cells (ECs) is well-known to increase endothelial permeability by disassembly of adherens junctions (AJs) and actinomyosin contractility mechanism involving myosin light chain (MLC) phosphorylation, we investigated the effects of bone marrow-derived progenitor cells (BMPCs) on the thrombin-induced endothelial permeability response.
We observed that addition of BMPCs to endothelial monolayers at a fixed ratio prevented the thrombin-induced decrease in transendothelial electrical resistance, a measure of AJ integrity, and increased mouse pulmonary microvessel filtration coefficient, a measure of transvascular liquid permeability. The barrier protection was coupled to increased vascular endothelial cadherin expression and increased Cdc42 activity in ECs.
Using small interfering RNA (siRNA) to deplete Cdc42 in ECs, we demonstrated a key role of Cdc42 in signaling the BMPC-induced endothelial barrier protection. Endothelial integrity induced by BMPCs was also secondary to inhibition of MLC phosphorylation in ECs. Thus BMPCs interacting with ECs prevent thrombin-induced endothelial hyperpermeability by a mechanism involving AJ barrier annealing, inhibition of MLC phosphorylation, and activation of Cdc42.
Yidan D. Zhao,* Hiroshi Ohkawara,* Stephen M. Vogel, Asrar B. Malik, and You-Yang Zhao
Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois
Since thrombin activation of endothelial cells (ECs) is well-known to increase endothelial permeability by disassembly of adherens junctions (AJs) and actinomyosin contractility mechanism involving myosin light chain (MLC) phosphorylation, we investigated the effects of bone marrow-derived progenitor cells (BMPCs) on the thrombin-induced endothelial permeability response.
We observed that addition of BMPCs to endothelial monolayers at a fixed ratio prevented the thrombin-induced decrease in transendothelial electrical resistance, a measure of AJ integrity, and increased mouse pulmonary microvessel filtration coefficient, a measure of transvascular liquid permeability. The barrier protection was coupled to increased vascular endothelial cadherin expression and increased Cdc42 activity in ECs.
Using small interfering RNA (siRNA) to deplete Cdc42 in ECs, we demonstrated a key role of Cdc42 in signaling the BMPC-induced endothelial barrier protection. Endothelial integrity induced by BMPCs was also secondary to inhibition of MLC phosphorylation in ECs. Thus BMPCs interacting with ECs prevent thrombin-induced endothelial hyperpermeability by a mechanism involving AJ barrier annealing, inhibition of MLC phosphorylation, and activation of Cdc42.
Yidan D. Zhao,* Hiroshi Ohkawara,* Stephen M. Vogel, Asrar B. Malik, and You-Yang Zhao
Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois
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