Check out Organovo Holdings Inc. v. Dimitrov, case number 10536, in the Delaware Court of Chancery.
Also, Organovo Holdings Inc. v. Simeon Research LLC, case number 9563, in the same venue.
That is how we deal with fraudulent entities. Sucks to be you.
Thanks for the info Stan. June should be interesting with fiscal year end update, partner presentations further validating future uses, and hopefully early kidney testing for select clients commencing (if it hasn't already!)
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Member since: Apr 14, 2016
Ignored since: Apr 14, 2016
We were there in Aug also just after the road reopened. One buddy swam in the river, I was content to soak my feet.
I agree, it's a great park and area. Backpacked 58 miles there last summer with 4 buddies. Had to visit before all the glaciers melted!
Thanks drz for investing the time and money to attend and report back to the rest of us. One of my favorite cities for food and fun, I'm sure you had a great time.
Anybody have any info on what progress has been made on the use of 3D bioprinted human breast cancer for in vitro screening of therapeutics targeted against cancer progression using patients own cells?
Or what Janssen ( Johnson & Johnson) is doing with their tissues (or what tissues they are using?)
Somebody needs to go to happy hour where the lab techs hangout and buy them a few drinks!
My take aways from these SOT poster abstracts are the continued validation of the liver product from both internal and external sources and the disclosure of potential partner / customer Astellas Pharma Inc from Japan. Keith alluded to the faster pace of approval / adoption in that market for tissue products.
Don't confuse the failed theory of Supply Side (Reaganomics) with the core ideas in microeconomics. Supply, demand and equilibrium.
2001 Functional Evaluation of Bioprinted Human Liver
Tissue as a Liver Injury Model
K. Tetsuka1, M. Ohbuchi1, H. Moriguchi1, E. Kobayashi2, M. Kanki2, A.
Miyashita1 and K. Tabata1. 1Analysis & Pharmacokinetics Research
Labs., Astellas Pharma Inc., Tsukuba-shi, Japan and 2Drug Safety
Research Labs., Astellas Pharma Inc., Osaka-shi, Japan. Sponsor:
Purpose: As drug-induced liver injury is a major cause of drug withdrawal
from market, culture models that can accurately predict and evaluate
the toxic potential of chemicals are required. Three-dimensional (3D)
bioprinting technology enables the alignment of different cell types in a
spatially-controlled manner. Here, we characterized the long- and shortterm
effects of acetaminophen (APAP) in a 3D-bioprinted model of the
human liver. Materials and Methods: The exVive3D Liver (Organovo
Holdings Inc., San Diego, CA, USA) was used as a three-dimensional
human liver tissue model (3DHLT). Briefly, 3DHLTs were constructed
from human hepatocytes, stellate cells, and endothelial cells of the
umbilical vein using a Novogen Bioprinter (Organovo Holdings Inc.). To
measure the long-term effects of APAP, 3DHLTs underwent treatment
with APAP at 0, 0.3, 1, 3, 10, or 30 mM for 1, 7, 14, or 28 days. To measure
the short-term effects of APAP, 3DHLTs underwent treatment with APAP
at 30 mM for 6 h, followed by either termination of culture or further culture
without APAP for 1, 3, or 18 h as a washout stage. Intracellular ATP
and glutathione (GSH) levels in these specimens were then measured
as described in the manufacturer’s instructions. Results and Discussion:
Treatment of 3DHLTs with APAP at 30 mM for 1 day significantly reduced
mean ATP level to 27.9% of that of controls. Prolonged APAP
treatment also reduced mean ATP levels, even with treatment at lower
concentrations. IC50 values decreased over the APAP treatment period.
Short-term APAP treatment of 3DHLTs at 30 mM for 6 h significantly reduced
mean GSH level to 56% of that
2003 Utilization of exVive 3D Human Liver Tissues for
the Evaluation of Valproic Acid-Induced Liver
C. Grundy, R. Smith, J. Nickel, R. N. Hardwick and D. G. Nguyen.
Tissue Applications, Organovo, Inc., San Diego, CA; Tissue Testing,
Organovo, Inc., San Diego, CA. Sponsor: D. Nguyen.
Conventional (2D) cell culture models do not accurately reflect the
complex microenvironment of liver tissue, and pre-clinical animal trials
are often inadequate due to species-specific variation in hepatocellular
functions. 3D bioprinted human liver tissues better approximate
human tissue composition and physiology, and therefore enable the
assessment of drug-induced liver injury (DILI) and related mechanisms
at the tissue level, including biochemical and histologic outcomes. In
this study, we assessed the DILI response to Valproic Acid (VPA), a compound
known to induce steatosis in humans, in 3D-bioprinted human
liver tissue mimetics comprised of primary hepatocytes, hepatic stellate
cells, and endothelial cells. 3D-bioprinted human liver tissues (exVive3D;
Organovo, San Diego CA), were treated daily for 14 days with VPA, which
resulted in dose-dependent decreases in tissue health as assessed by
ATP, GSH and histology. Tissue ATP levels were decreased 70% and
45% relative to vehicle following 14 day treatment with 1mM and 5mM
VPA, respectively. Following the observations seen with ATP levels, the
higher doses of 200µm, 1mM and 5mM were selected to further evaluate
the mechanism of observed tissue damage. GSH levels were measured
at 24hr and 72hr to determine the acute oxidative stress response.
A significant decrease in the ratio of reduced to oxidized GSH was observed
at 24hr treatment, indicating increased oxidative stress. Recovery
of GSH ratios was noted with 200µm and 1mM treatment groups at
72hr, while the 5mM treatment group exhibited prolonged oxidative
stress. Histological evaluation of tissues revealed dose-dependent damage
with abundant vacuolization in 5mM VPA treate
1996 Modeling Drug-Induced Hepatic Fibrosis In Vitro
Using Three-Dimensional Liver Tissue Constructs
L. M. Norona2,3, D. G. Nguyen1, D. A. Gerber3, S. C. Presnell1 and
E. L. LeCluyse2,3. 1Organovo, Inc., San Diego, CA; 2The Hamner
Institutes, Research Triangle Park, NC and 3The University of North
Carolina at Chapel Hill, Chapel Hill, NC.
Compound-induced hepatotoxicity leading to fibrosis remains a challenge
for human toxicity risk assessment. Latency to detection and lack
of early biomarkers make it difficult to characterize the dynamic and
complex intercellular interactions that occur during progressive liver
injury. Animal models only partially address this challenge however; the
development of a truly mechanistic understanding requires the use of
human tissue-like model systems that can be interrogated over time
to identify key cellular and molecular events underlying fibrogenesis.
Here we demonstrate the utility of bioprinted tissue (exVive3D Human
Liver, Organovo) comprising hepatocytes, stellate cells and endothelial
cells to conduct repeated low concentration modeling of compound-induced
liver injury leading to fibrosis. Significant time dependent elevations
of LDH were observed for both TAA (by Day 3) and MTX (by Day
11) and were accompanied by the acquisition of a fibrogenic phenotype
as supported by preliminary cytokine, gene expression data, and histologic
evidence of collagen deposition. In comparison, treatment with
TGF-β1, a known pro-fibrogenic cytokine, yielded moderate to severe
fibrotic change in the tissue with little evidence of hepatocellular damage.
These preliminary data provide strong proof-of-concept that 3D
bioprinted liver tissues can recapitulate drug-, chemical- and TGF-β1-
induced fibrogenesis on a cellular, molecular, and histological basis. The
use of this novel system and strategy will enable the integration of initial
and adaptive cellular mechanisms during the onset and progression of
injury to better characterize key attributes
I tried posting them all but they seem to be stuck in the cloud.....maybe they'll show up eventually.
1959 Inflammatory Response of Kupffer Cells in 3D
Bioprinted Human Liver Tissues
R. N. Hardwick, J. Hampton, D. Perusse and D. G. Nguyen. Tissue
Applications, Organovo, Inc., San Diego, CA.
Hepatic inflammation, mediated by Kupffer cells (KC), can exacerbate
hepatocellular damage during drug-induced liver injury. KC are often
employed in co-culture with hepatocytes to investigate the potential
for inflammation in response to stimuli, such as the prototypical inducer
lipopolysaccharide (LPS); however, such systems seldom include other
nonparenchymal cells and fail to recapitulate the complex 3D interactions
present in native liver. In the current study, LPS-mediated activation
of KC at 24 and 72hrs was investigated in 3D bioprinted human liver
tissues (exVive3D; Organovo, San Diego, CA). Induction of pro- and anti-inflammatory
cytokines was measured via electrochemiluminescence
in tissues comprising primary hepatocytes, stellate cells, and endothelial
cells (Hep:KC-), and compared to tissues containing KC. Independent
experiments were conducted comparing two KC donors (Hep:KC+D1
♂ and Hep:KC+D2 ♀) with all other cell donors held constant. LPS
stimulated TNF-α, IL-1β, IL-12p70, IL-10, IL-2, IL-13, and IL-4 levels in
Hep:KC+D1 tissues at 24hrs compared to untreated, with sustained induction
to 72hrs. TNF-α, IL-10, and IL-8 exhibited greater induction in
Hep:KC+D1 tissues compared to Hep:KC-. All cytokines were increased
at 24hrs in Hep:KC+D2 tissues treated with LPS compared to untreated,
with sustained induction of IL-8, IL-1β, IFN-γ, IL-2, and IL-12p70. IL-8,
IL-6, and IL-10 induction was greater in Hep:KC+D2 tissues compared
to Hep:KC-. To compare donor-specific responses to LPS, cytokine levels
were normalized to untreated Hep:KC-, and the fold change in LPStreated
Hep:KC+ tissues was calculated. Patterns of LPS-induced cytokine
release were distinct between KC donors, with greater induction
in the female donor. However, IL-1β, IL-10, IL-2, and IL-13 exhibited no