Miami, FL, United States
Miami, FL, United States

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Patent
Tissuetech | Date: 2016-11-10

Disclosed herein, in certain instances, are methods of inhibiting osteoclast differentiation, bone resorption, bone formation, and bone remodeling in an individual in need thereof, comprising administering to the individual a composition comprising substantially fetal support tissue product including amniotic membrane and umbilical cord or an extract thereof, or a composition comprising substantially isolated HC-HA complex.


Patent
Tissuetech | Date: 2016-07-20

Disclosed herein, in certain instances, are tissue grafts derived from UCAM. Further disclosed herein, in certain instances, are use for tissue grafts derived from UCAM.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 286.52K | Year: 2015

DESCRIPTION provided by applicant Proliferative vitreoretinopathy PVR is characterized by membranes that develop on the surface of the retina after rhegmatogenous retinal detachments RRDs Because PVR membranes exert tractional forces on the retina they are the leading cause of failure after RRD surgery Despite additional surgical interventions the visual outcome still remains poor Prevention of PVR during the initial RRD surgery is preferable and will avoid such recurrent retinal detachment or even blindness Unfortunately all previous attempts to prevent PVR formation using different pharmacologic agents have been unsuccessful The two main pathological hallmarks of PVR membranes are proliferation and epithelial mesenchymal transition EMT of retinal pigment epithelium RPE cells RPE cells play a pivotal role in maintaining photoreceptor function and are normally differentiated and mitotically quiescent due to contact inhibition RRDs allow RPE cells to be dispersed in the vitreous cavity and become exposed to growth factors e g EGF FGF TGF VEGF and TNF and inflammatory cytokines e g IFN which result in proliferation and EMT into fibroblasts or myofibroblasts Our recent discovery provides insight into the mystery of how growth factors control the proliferation and EMT of RPE cells Using post confluent ARPE cells in an in vitro model we demonstrated that proliferation is coupled with EMT when contact inhibition is perturbed by EGTA followed by exposure to EGF and or FGF which activate canonical Wnt signaling In contrast proliferation ceases with full blown EMT followed by exposure to TGF which activates Smad ZEB signaling This baseline characterization establishes a framework for discovering new drugs which can prevent PVR by targeting both proliferation and EMT Transplantation of cryopreserved amniotic membrane AM has become a standard surgical procedure for ocular surface reconstruction to deliver anti inflammatory anti scarring and anti angiogenic actions to promote wound healing Recently we have purified and characterized an active AM matrix component termed heavy chain hyaluronic acid pentraxin HC HA PTX complex which retains AMandapos s aforementioned therapeutic actions In this SBIR Phase I application we propose to prove the concept that HC HA PTX can inhibit both canonical Wnt signaling and TGF induced Smad ZEB signaling in RPE cells to inhibit proliferation and EMT respectively Successful completion of these aims will allow us to move to Phase II in order to gather critical pre clinical safety and efficacy data for the IND submission to the FDA so that we may examine its therapeutic potential as a new class of biologics to prevent PVR in human patients PUBLIC HEALTH RELEVANCE Our published and preliminary studies support the hypothesis that the HC HA PTX complex purified from human amniotic membrane can suppress both proliferation and EMT of human RPE cells In this Phase I application we propose to prove the concept so that we may proceed with pre clinical safety and efficacy studies in Phase II to gather critical data for the IND application to the FDA Our ultimate goal is to develop HC HA PTX as a new class of biologics to prevent PVR in human patients Furthermore the success of achieving this product development program will pave the way to deploy HC HA PTX as a new class of biologics to treat inflammatory scarring diseases in the eye and other parts of the body


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 454.71K | Year: 2016

Prevention of Proliferative Vitreoretinopathy by HC HA PTX Summary Proliferative vitreoretinopathy PVR is characterized by membranes that develop on the surface of the retina after rhegmatogenous retinal detachments RRD during which time RPE cells are dispersed into the vitreous cavity where they lose contact inhibition and are exposed to multiple growth factors and cytokines This pathological setting promotes proliferation and EMT of RPE cells to fibroblasts or myofibroblasts that produce intravitreal membranes These PVR membranes exert tractional forces on the retina and become the leading cause of failure after RRD surgery Despite additional surgical interventions the visual outcome still remains poor Prevention of PVR during the initial RRD surgery could improve the visual success rate Unfortunately all previous attempts using different agents have been unsuccessful Using an in vitro RPE cell culture model we have reported that following perturbation of contact inhibition of RPE cells EGF and FGF upregulate while TGF downregulates canonical Wnt signaling in the proliferative phase but TGF promotes canonical TGF Smad ZEB signaling in the irreversible scarring phase of EMT We have successfully purified and characterized HC HA PTX from amniotic membrane AM and have reported that this unique matrix is responsible for AMandapos s anti inflammatory anti scarring and anti angiogenic therapeutic actions HC HA PTX is formed by tight association between pentraxin PTX and HC HA which consists of high molecular weight hyaluronic acid HA covalently linked to heavy chain HC of inter trypsin inhibitor I I through the catalytic action of tumor necrosis factor stimulated gene TSG Through Phase I support we have proven the concept that HC HA PTX can be a novel biologic to prevent PVR by inhibiting proliferation and EMT in the aforementioned in vitro model that has been optimized to better mimic in vivo pathological processes of PVR regarding cell density growth factor stimulation and measurement methods We have developed the potency assay that is required as an in process control of the manufacturing of HC HA PTX from different donors demonstrated the safety i e lack of cytotoxicity and the efficacy of HC HA PTX over a wide range of doses demonstrated the efficacy of HC HA PTX but not HA in inhibiting proliferation and gel contraction caused by both ARPE cells and primary human RPE cells and delineated the mode of action of HC HA PTX in inhibiting the aforementioned Wnt and TGF signaling These accomplishments allow us to propose in this Phase II application to scale up the manufacturing of HC HA PTX by combining AM and umbilical cord UC from the same donor Aim to establish the release criteria and the stability of the HC HA PTX formulation via reproducible GMP manufacturing Aim and to determine the safety and efficacy of intravitreal injection of HC HA PTX in our recently established rabbit PVR model Aim Collectively we would like to gather necessary and sufficient pre clinical data for an IND submission to the FDA so that the Company can capture a unique business opportunity by deploying this novel biologic to fulfill the unmet global need of treating this severe retinal blinding disease Narrative Our published data and the Phase I progresses have proven the concept that the HC HA PTX complex purified from human amniotic membrane can suppress proliferation migration gel contraction and EMT of human RPE cells Using an improved in vitro RPE culture model to better mimic the in vivo pathological processes of PVR we have developed the potency assay as an in process control of the manufacturing process of HC HA PTX demonstrated the safety and the efficacy of HC HA PTX in inhibiting both abnormal proliferation and EMT in the optimized in vitro RPE model and delineated the mode of action of HC HA PTX in inhibiting the pathological Wnt and TGF signaling In addition we have reproduced a rabbit PVR model so that in this Phase II application we may scale up the manufacturing of HC HA PTX by combining both AM and umbilical cord UC from the same donor Aim establish the release criteria and the shelf life of the HC HA PTX formulation via reproducible GMP manufacturing Aim and determine the safety and efficacy of intravitreal injection of HC HA PTX in the established rabbit PVR model Aim The successful completion of these three Aims will allow us to gather sufficient pre clinical data for an IND submission to the FDA so that the Company may deploy HC HA PTX as a biologic to treat this serious retinal blinding disease


Provided herein are methods for the production of native and reconstituted hyaluronan (HA) complexes containing pentraxin-3 (PTX3) and heavy chain 1 (HC1) of inter alpha inhibitor (II). Compositions containing the complexes and therapeutic methods using the complexes are provided. Combinations and kits for use in practicing the methods also are provided.


Compositions and preparations of fetal support tissue that prevent or reduce the proliferation and epithelial-mesenchymal transition (EMT) of epithelial cells, wherein the epithelial cells may be human epithelial cells and the human epithelial cells may be conjunctival, retinal, corneal, limbal, or renal epithelial cells. Methods of preventing or reducing the proliferation, cell migration, and EMT of epithelial cells in an individual in need thereof, wherein the epithelial cells may be human epithelial cells and the human epithelial cells may be conjunctival, retinal, corneal, limbal, or renal epithelial cells. Methods of preventing or treating proliferative vitreoretinopathy in an individual in need thereof.


Patent
Tissuetech | Date: 2016-01-14

Disclosed herein, in certain instances, are tissue grafts derived from UCAM. Further disclosed herein, in certain instances, are use for tissue grafts derived from UCAM.


Patent
Tissuetech | Date: 2016-06-28

Disclosed herein, in certain instances, are tissue grafts derived from UCAM. Further disclosed herein, in certain instances, are use for tissue grafts derived from UCAM.


The invention relates generally to the fields of biology and health sciences. More particularly, the invention relates to compositions and methods for modulating cellular physiology and pathological processing using a combination of compounds that can be found in amniotic membrane tissue and umbilical cord tissue preparations.


Compositions having a combination of specific biological components have been found to exert a number of useful effects in mammalian cells, including modulating TGF signaling, apoptosis, and proliferation of mammalian cells, as well as decreasing inflammation in mice. These components can be obtained commercially, or can be prepared from biological tissues such as placental tissues. Placental amniotic membrane (AM) preparations described herein include AM pieces, AM extracts, AM jelly, AM stroma, and mixtures of these compositions with additional components. The compositions can be used to treat various diseases, such as wound healing, inflammation and angiogenesis-related diseases.

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