Browsing by Author "Traktuev, Dmitry"

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    ADIPOSE-DERIVED STROMAL CELLS PROMOTE SURVIVAL OF ENDOTHELIAL CELLS AND KERATINOCYTES IN WOUND HEALING MODEL
    (Office of the Vice Chancellor for Research, 2012-04-13) Knowles, Kellen A.; Traktuev, Dmitry; March, Keith L.
    Burn wounds are a significant medical challenge today. Current treat-ment includes the use of skin grafts or wound healing scaffolds to protect the wound and promote healing. However, pre-existing conditions and fac-tors such as smoking can compromise normal healing thru decreased growth factor production, prolonged inflammation, tissue hypoxia, reduced cellular migration and ECM deposition, and impaired revascularization, making the wound more susceptible to infection. Adult pluripotent cells have been proposed as a therapy for multiple dis-orders because they have been shown to decrease inflammation and pro-mote host tissue preservation and angiogenesis. Adipose-derived stromal cells (ASC) are a population of mesenchymal, pluripotent cells derived from adipose tissue. Compared to bone marrow derived MSC, ASC can be easily obtained thru minimally invasive procedures. It has been shown in previous studies that ASC improved wound closure in normal and diabetic mice and stimulated proliferation of human dermal fibroblasts, increasing the epitheli-alization of cutaneous wounds. The next challenge is to find a clinically relevant cell-delivery method. In light of this, we propose the use of current clinical wound healing scaf-folds as a delivery vehicle for ASC in combination with endothelial cell (EC) and keratinocytes. We hypothesize that that ASC will promote keratinocyte and EC survival (both are used clinically), thus promoting epithelialization and neovascularization of graft. The use of ASC, EPC and keratinocytes in combination with wound healing scaffolds currently used by physicians, such as Integra is a novel combination and will provide a faster transition to clinic if it is found to be efficacious. Our lab has shown that ASC promote survival of EC on Integra and sup-port the formation of vascular-like cord structures. Factors secreted by ASC promote keratinocytes ingrowth in a wound closure assay. Keratinocytes also showed increased survival when cultured with ASC.
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    Subcutaneous injection of adipose stromal cell-secretome improves renal function and reduces inflammation in established acute kidney injury
    (Springer Nature, 2024-04-24) Ullah, Md Mahbub; Collett, Jason A.; Monroe, Jacob C.; Traktuev, Dmitry; Coleman, Michael; March, Keith L.; Basile, David P.; Anatomy, Cell Biology and Physiology, School of Medicine
    Background: Adipose stromal cells (ASC) are a form of mesenchymal stromal cells that elicit effects primarily via secreted factors, which may have advantages for the treatment of injury or disease. Several previous studies have demonstrated a protective role for MSC/ASC on mitigating acute kidney injury but whether ASC derived factors could hasten recovery from established injury has not been evaluated. Methods: We generated a concentrated secretome (CS) of human ASC under well-defined conditions and evaluated its ability to improve the recovery of renal function in a preclinical model of acute kidney injury (AKI) in rats. 24 h following bilateral ischemia/reperfusion (I/R), rats were randomized following determination of plasma creatinine into groups receiving vehicle -control or ASC-CS treatment by subcutaneous injection (2 mg protein/kg) and monitored for evaluation of renal function, structure and inflammation. Results: Renal function, assessed by plasma creatinine levels, recovered faster in ASC-CS treated rats vs vehicle. The most prominent difference between the ASC-CS treated vs vehicle was observed in rats with the most severe degree of initial injury (Pcr > 3.0 mg/dl 24 h post I/R), whereas rats with less severe injury (Pcr < 2.9 mg/dl) recovered quickly regardless of treatment. The quicker recovery of ASC-treated rats with severe injury was associated with less tissue damage, inflammation, and lower plasma angiopoietin 2. In vitro, ASC-CS attenuated the activation of the Th17 phenotype in lymphocytes isolated from injured kidneys. Conclusions: Taken together, these data suggest that ASC-CS represents a potent therapeutic option to improve established AKI.
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    Vascular and Cardiac Adult Stem Cell Therapy Center
    (Office of the Vice Chancellor for Research, 2010-04-09) March, Keith; Murphy, Michael; Petrache, Irina; Evans-Molina, Carmella; Farag, Sherif; Traktuev, Dmitry; Saadatzadeh, Reza; Johnstone, Brian; Schweitzer, Kelly; Rosen, Elliot; Chen, Peng-Sheng
    The mission of the Vascular and Cardiac Adult Stem Cell Therapy Center (VC-CAST) is the discovery and clinical translation of therapies involving transplantation of adult stem cells into patients with debilitating diseases. To accomplish this, VC-CAST fosters multidisciplinary research collaborations that address both biology of adult stem cells that are readily available, and the translation of their study from the laboratory into clinical trials. The use of such cells is highly feasible, and not ethically controversial, as they are derived from readily-available tissues such as fat and bone marrow. Since its inception, VC-CAST projects have been multidisciplinary, involving multiple clinical as well as basic departments of the School of Medicine. VC-CAST projects are also collaborative, with most of the projects having one or more industrial partners. A key partnership has also been established by the creation of the Veterans Affairs Center for Regenerative Medicine (VACRM) at the Roudebush VA Medical Center in Indianapolis, which will provide a unique referral site focusing on research and implementation of first-in-human trials in the fields of poor circulation, arthritis, wound healing, diabetes, and emphysema. Given the focus of VC-CAST researchers on translation, the center is active in pursuit of intellectual property that is critical to building corporate engagement and thus the enablement of translation to clinical trials. Signature center funding has allowed IUPUI investigators to try high-risk, high-reward ideas, which could not otherwise be funded readily, via either NIH or venture-capital methods. Most of these experiments are still ongoing, but have already led to discoveries of potentially critical significance to patients. The novelty of some of these discoveries promises to attract new funding, as well as to provide bases for potential licensing revenues and startup opportunities. This poster will highlight several of these projects, representative of center activities in their collaborative, multidisciplinary and translational and potentially commercializable aspects. Some key projects are as follows: • Based on recent completion of the Phase I/II clinical trial, “Stem cell Angiogenesis to promote limb salVagE (SAVE), a new randomized Phase III clinical trial testing the use of one’s own bone marrow-derived stem cells to save legs from amputation has been initiated, with Dr. Murphy as the national PI. • Adipose Stem Cells for Peripheral Arterial Disease. • Endometrial Regenerative Cells for Peripheral Arterial Disease. • Adipose Stem Cells for treatment of Heart Attack and prevention of Heart Failure. • Adipose Stem Cells for Emphysema and other Lung Diseases • Adipose Stem Cells for Prevention and Treatment of Diabetes • Isolation and Characterization of Endothelial and Mesenchymal Stem Cells from Term Human Placenta. • Isolation and Characterization of Endothelial Colony Forming Cells (ECFCs) from Human Adult Blood Vessels
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    Vascular and Cardiac Adult Stem Cell Therapy Center (VC-CAST)
    (Office of the Vice Chancellor for Research, 2011-04-08) March, Keith; Murphy, Michael; Petrache, Irina; Evans-Molina, Carmella; Traktuev, Dmitry; Johnstone, Brian; Clauss, Matthias; Hong, Soonjun; Gangaraju, Rajashekhar; Saadatzadeh, M. Reza; Schweitzer, Kelly; Rosen, Elliot; Farag, Sherif; Du, Yansheng; Chen, Peng-Sheng
    The mission of the Vascular and Cardiac Adult Stem Cell Therapy Center (VC-CAST) is the discovery and clinical translation of therapies involving transplantation of adult stem cells into patients with debilitating diseases. VC-CAST fosters multidisciplinary research collaborations that address the biology of adult stem cells that are readily available, as well as the translation of their study from the laboratory into clinical trials. The use of such cells is highly feasible, and not ethically controversial, as they are derived from readily-available tissues such as fat and bone marrow. VC-CAST projects involve partners from multiple clinical and basic departments of the School of Medicine. VC-CAST projects are also collaborative externally, with most projects having one or more industrial or academic external partners. A key partnership has also been established at the Roudebush VA Medical Center in Indianapolis by creation of the Veterans Affairs Center for Regenerative Medicine (VACRM), which will provide a unique referral site focusing on research and implementation of first-in-human trials in the fields of poor circulation, stroke, arthritis, wound healing, diabetes, and emphysema. Given the focus on translation, the center is active in pursuit of intellectual property that is critical to building corporate engagement and thus the enablement of translation to clinical trials. Signature Center funding has allowed IUPUI investigators to try high-risk, high-reward ideas, which could not otherwise be funded readily, via either NIH or venture-capital methods. Most of these experiments have already led to discoveries of potentially critical significance to patients. The novelty of some of these discoveries has attracted new funding, as well as provided bases for potential licensing revenues and startup opportunities. This poster will highlight several such projects, representative of center activities in their multidisciplinary, translational, and potentially commercializable aspects. Several key projects are as follows: • Saving Legs from Amputation o Bone Marrow Stem Cells: Based on our completion of the Phase I/II clinical trial, “Stem cell Angiogenesis to promote limb salVagE (SAVE), we have initiated a randomized Phase III clinical trial testing one’s own bone marrow-derived stem cells to save legs from amputation, with Dr. Murphy as national PI. o Fat-derived (Adipose) Stem Cells– we are testing the hypothesis that these are more potent than Bone Marrow-derived stem cells with new funding from a corporate partner as well as the Department of Defense. o Endometrial Regenerative Cells– further extending above efforts, with new NIH funding to study this allogeneic (non-self, “off-the-shelf”) cell type. • Treatment of Heart Attack and prevention of Heart Failure. New data this year shows Adipose Stem Cells protect from heart damage when given systemically. • Treatment of Emphysema and other Lung Diseases. Adipose Stem Cells markedly protect from cigarette smoke-induced emphysema, a generally untreatable condition. • Prevention and Treatment of Diabetes– Adipose Stem Cells can ameliorate diabetes. This work has attracted new Veterans Affairs funding this past year. • Treatment of Parkinson’s Disease by rescue of dopaminergic neurons from death. New funding attracted in the past year by the Signature Center led to preclinical data that extended prior work in stroke models to models of Parkinson’s Disease. These data suggest that the conditioned medium from ASCs can be useful in this debilitating condition, and form the basis for a new NIH application. • Treatment of Diabetic Retinopathy by vascular stabilization using adipose stem cells. This is a new project in the past year, and has generated encouraging early data which is being used in seeking further (external) funding. • Human Placenta as a stem cell source: Isolation and Characterization of Endothelial and Mesenchymal Stem Cells from Term Placenta. • Human Saphenous Vein as a cell source: Isolation and Characterization of Endothelial Colony Forming Cells (ECFCs) from Human Saphenous Vein can form the basis for vascular network formation.