Maria Siemionow

University of Illinois at Chicago, Chicago, Illinois, United States

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Publications (308)686.27 Total impact

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    ABSTRACT: Many more patients would benefit from vascularized composite allotransplantation if less toxic and safer immunosuppressive protocols will become available. Tolerance induction protocols with donor cells co-transplantation are one of the promising pathways to reduce maintenance immunosupressive regimens. We investigated the role of donor bone marrow cells (BMC), mesenchymal stromal cells (MSC) and in vivo created chimeric cells (CC) used as supportive therapies in a fully MHC-mismatched rat face transplantation model. Twenty-four fully MHC-mismatched hemiface transplantations were performed between ACI (RT1(a)) donors and Lewis (RT1(l)) recipients under combined seven-day immunosuppressive regimen of anti-αβ-T-cell receptor (TCR) monoclonal antibody and cyclosporin A. We studied four experimental groups-group 1: no cellular therapy; group 2: supportive therapy with BMC; group 3: supportive therapy with MSC; group 4: supportive therapy with CC generated in a primary chimera. We evaluated clinical and histological rejection grades, transplanted cells migration, donor-specific chimerism in the peripheral blood and bone marrow compartments, and CD4(+)/CD25(+) T-cell levels. Face allograft rejection was observed at 26.8 ± 0.6 days post-transplant (PT) in the absence of cellular therapy, at 34.5 ± 1.1 days for group 2, 29.3 ± 0.8 days for group 3, and 30.3 ± 1.38 PT for group 4. The longest survival was observed in allografts supported by co-transplantation of BMC. All support in cellular therapies delayed face allograft rejection by chimerism induction and/or immunomodulatory properties of co-transplanted cells. Survival time was comparable between groups, however, further studies, with different cell dosages, delivery routes and delivery times are required.
    No preview · Article · Dec 2015 · Archivum Immunologiae et Therapiae Experimentalis
  • Maria Siemionow
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    ABSTRACT: Over the past 20 years, the fields of biomaterial sciences and tissue engineering have evolved into new clinically relevant applications including regenerative medicine and cell based therapies. Tissue engineering therapies are based on different types of materials and scaffolds combined with cells and submitted to engineering processes in order to create bio-scaffolds which will improve or replace biological functions. Despite the effort, only a few therapies, such as bone, cartilage and nerve, succeeded in clinical applications. Furthermore, the major drawback in standard application of these therapies was the critical size defects which could be covered with engineered materials, as well as inability to provide sustainable vascular supply to the created bio-scaffolds. In 1998, the first successful hand transplantation was performed in France, and the field of vascularized composite allotransplantation (VCA) was introduced into the armamentarium of reconstructive surgery (Dubernard in Am J Transplant 5(6):1580–1, 2005; Petruzzo et al. in Am J Transplant 6(7):1718–24, 2006; Lanzetta et al. in Transplantation 79(9):1210–4, 2005). As a result, a new generation of transplants including hand, face, larynx abdominal wall, lower extremities and penile transplantation became available to patients who had lost these unique organs and were previously unable to achieve restored function using standard reconstructive procedures. Ethical debate on the need for life-long immunosuppressive therapy to prevent rejection of the VCA overshadowed the success of face and hand transplants. Thus, a new, challenging opportunity developed to combine approaches of tissue engineering and regenerative medicine and ultimately restore the framework, function, aesthetics and survival of the VSA transplants. This overview presents the unique opportunities of merging established and new technologies into the burgeoning field of reconstructive transplantation.
    No preview · Article · Dec 2015 · Journal of Materials Science Materials in Medicine

  • No preview · Article · Sep 2015
  • Article: LOP05
    M. Bozkurt · F. Ceran · S. Uygur · C. Ozturk · M. Siemionow

    No preview · Article · Aug 2015 · Plastic & Reconstructive Surgery
  • Article: LOP05
    M. Bozkurt · F. Ceran · S. Uygur · C. Ozturk · M. Siemionow

    No preview · Article · Aug 2015 · Plastic & Reconstructive Surgery
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    ABSTRACT: Vapocoolant sprays are commonly used to minimize pain following minor interventions such as venipuncture, shave biopsy or needle insertion. Although these sprays have been widely used in clinical practice, little is known about their effect on microcirculation or cutaneous blood flow. To evaluate the real-time effect of a topical vapocoolant using a well-established, rat cremaster muscle microcirculatory model, allowing direct measurement of changes in vessel diameter, capillary density and leukocyte behaviour. Fifty rats were divided into a control and four experimental groups: group 1: 4 s spray with vapocoolant at 18 cm distance; group 2: 10 s spray at 18 cm distance; group 3: 4 s spray at 8 cm distance; and group 4: 10 s spray at 8 cm distance. Vessel diameters, capillary density and leukocyte behaviour were monitored for 1 h thereafter. Muscle was harvested for immunohistochemistry analysis of proangiogenic markers (vascular endothelial growth factor and von Willebrand factor), leukocyte behaviour markers (E-selectin, vascular cell adhesion molecule, intercellular adhesion molecule), pimonidazole-hypoxia staining and ApopTag (Millipore, USA) staining for apoptosis. Gene expression for inflammatory markers (interleukin [IL]-1β, IL-2, IL-4, IL-6, IL-10, tumour necrosis factor-alpha and interferon-gamma) was evaluated using polymerase chain reaction and myeloperoxidase assay for inflammation was performed. The use of refrigerant spray decreased vessel diameter and capillary density initially, although none of these decreases were statistically significant. Polymerase chain reaction showed no significant changes. The myeloperoxidase assay showed statistically significant increase in myeloperoxidase activity in groups 2, 3 and 4. Immunohistochemistry was negative for angiogenic and proinflammatory markers. The lack of statistically significant changes in vessel diameter and inflammatory markers corroborated the safety on microcirculation.
    No preview · Article · May 2015
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    ABSTRACT: Vascularized composite allografts can undergo immune-mediated rejection, and skin biopsies are needed for monitoring of the transplant. However it is an invasive method, and requires processing time and pathological assessment. The purpose of this study is to use a new noninvasive monitoring method of the reflectance confocal microscopy (RCM) to determine severity of the allograft rejection on rats. Five groin flap allotransplantation were performed between 10 male Sprague-Dawley rats. Immunosuppressive therapy with cyclosporine A was given to the recipients during 10 days after surgery and was ended at the 10th postoperative days to allow acute transplant rejection. Following cessation of CsA, concomitant RCM evaluation and skin biopsy was performed every other day from each animal until total rejection of the allograft. Complete rejection of the allograft took nearly about 10 days and 4 or 5 RCM evaluation and skin biopsy was performed from each rat during this period. A total of 17 specimens were evaluated. A scoring system was developed based on the RCM findings. Skin biopsies were evaluated according to the Banff 2007 working classification criteria. RCM evaluation revealed epidermal irregularity and collagen destruction, however mild perivascular inflammation and degeneration of the basal epidermal layer were observed in early and late rejection period respectively with histopathologic evaluation. High correlation was found between the RCM scores and histopathologic grading. The RCM may be the useful tool to reduce the need for skin biopsy for monitoring of the skin containing vascularized composite allograft. © 2015 Wiley Periodicals, Inc. Microsurgery, 2015. © 2015 Wiley Periodicals, Inc.
    Full-text · Article · May 2015 · Microsurgery
  • Article: Abstract 50
    Joanna Cwykiel · Medhat Askar · Grzegorz Kwiecien · Maria Siemionow

    No preview · Article · Apr 2015 · Plastic & Reconstructive Surgery
  • maria siemionow · can ozturk

    No preview · Chapter · Jan 2015
  • Raffi Gurunluoglu · Maria Z. Siemionow · Tommaso Falcone
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    ABSTRACT: Heterotopic vascularized ovarian autotransplantation using immediate revascularization through microvascular anastomosis was developed in the sheep model with the goal to reduce the ischemic interval after reimplantation of an ovary and to improve the reproductive potential of these transplants. The current chapter is assembled to highlight the experimental model: the applied anatomy and the operative technique along with a comprehensive review of vascularized ovarian transplantation studies in animal models and human subjects since the development of this model.
    No preview · Chapter · Jan 2015
  • Michal Molski · Ilker Yazici · Maria Z. Siemionow
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    ABSTRACT: Ischemia — reperfusion injury (IRI) is a serious complication of revascularisation that biases a result of many surgical procedures. The pathophysiology of IRI is very complex and still not fully understood. For years a laboratory model of muscle ischemia reperfusion have been developed to provide reliable scientific tool for observation of IRI and investigation of possible therapeutic strategies. Cremaster muscle model of IRI plays an important role in research of IRI due to its similarity to clinical scenarios of limb ischemia, transplantation, replantation. This model provides unique opportunity to visualize important events that occur during reperfusion like capillary perfusion, leukocyte-endothelial interaction, microvasculature response and endothelial permeability. It is a potent model for intravital investigation of muscle microcirculation subjected to IRI.
    No preview · Chapter · Jan 2015
  • Raffi Gurunluoglu · Maria Z. Siemionow
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    ABSTRACT: The microsurgical groin skin flap in the rat has achieved wide spread acceptance as this experimental model offers an inexpensive, practical and effective instrument to practice microvascular anastomosis as well as to investigate numerous research questions. The current chapter reviews the standard groin flap model and its various modifications in different shapes and sizes based on precise description of flap design and vascular anatomy. Surgeon’s consistency in the design and technique is critically important to obtain reproducible and reliable models.
    No preview · Chapter · Jan 2015
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    ABSTRACT: PURPOSE: Peripheral nerve injury (PNI) repair is a challenging task, resulting in unsatisfactory outcomes. Rat epineural sheath conduit supported with rat bone marrow-derived stromal cells demonstrated neuroregenerative potential. To bring this approach closer to clinical applications we developed a new biologic construct for nerve regeneration - human epineural conduit (hEC) consisting of human epineural sheath (hES) filled with human mesenchymal stem cells (hMSC). The aim of this study was to assess the feasibility of hEC on the PNI repair in the nude rat model. METHODS: Sciatic nerve defect (20mm) was created in 24 nude male rats. Animals were divided into four experimental groups: Group 1 - no repair; Group 2 - autograft; Group 3 - hES filled with saline; and Group 4 - hEC (supported with 3-4 x 10^6 hMSC ). hES was created by fascicles removal using pull-out technique. To ensure homogenicity of hMSC, cells were cultured for 14 days and immunostained for hMSC-specific markers prior to injection into the hES. Outcome assessment included: sensory pinprick (PP) and motor toe-spread (TS) tests at 1, 3, 6, 12 weeks. Somatosensory evoked potentials (SSEP), gastrocnemius muscle index (GMI), histomorphometry, fluorescent immunostaining for GFAP, NGF, S-100, HLA I / II, vWF and laminin B2 were performed 12 weeks post-surgery. RESULTS: Cultured hMSC expressed CD105, CD73 and CD90, and lacked expression of CD45, CD34, CD14, CD11b, CD79a, CD19 and HLA-DR surface molecules. No leakage of cells was observed at the time of injection during conduit implantation. hEC maintained its shape and integrity at 12 weeks following repair. No local inflammation or scarring was observed at the end of the follow up. Clinical evaluation and SSEP analysis confirmed sciatic nerve recovery in groups 3 and 4 with outcomes comparable to nerve autograft repair. Immunostaining showed presence of the hMSC in the conduit at 12 weeks post-implantation. Quantitative nerve and muscle histological analysis is currently in progress. CONCLUSION: The feasibility of the application of hEC for restoration of PNI was successfully confirmed in this study. The functional outcomes following the use of hEC were comparable to the golden standard of autograft repair. hEC is a promising new technology for regeneration of long nerve gap defects which combines the effect of neurotropic properties of hES and immunomodulating properties of hMSC.
    No preview · Article · Oct 2014 · Plastic & Reconstructive Surgery
  • Article: Abstract 28

    No preview · Article · Apr 2014 · Plastic and Reconstructive Surgery
  • Wojciech Konczalik · Maria Siemionow
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    ABSTRACT: Management of soft tissue deficits resulting from congenital abnormalities, trauma, systemic disease, and tumors is a particularly challenging field of plastic and reconstructive surgery. Fat grafting, a technique traditionally used in the correction of facial asymmetry, is commonly seen in aesthetic procedures which use the grafted fat for soft tissue augmentation and recontouring. Despite its widespread use in reconstruction and aesthetic surgery, therapeutic modalities applied in fat grafting are crude and the results of this intervention are unpredictable. The aim of this review was to present the most recent evidence regarding experimental studies and designs which confirmed or disproved fat volume expansion or fat maintenance after autologous fat grafting.
    No preview · Article · Apr 2014 · Annals of plastic surgery
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    ABSTRACT: Currently, only a few large animal models, including swine, dog, and nonhuman primate, are described for composite face transplantation studies and the literature lacks reports on the large animal model of composite auricular transplantation. Large animal models offer better understanding of the immunological mechanisms and major histocompatibility complex characterization and, for this reason, are preferred to the small animal models for the assessment of new immunosuppressive tolerance induction protocols. Thus, the aim of this study was to demonstrate feasibility of dissection and exploration of vascular territories of the hemifacial and auricle transplantation models in the sheep cadavers. Ten cadaver sheep heads were studied. The vascular territories of the composite hemifacial flap and composite auricle flap were defined by anatomical dissection. Methylene blue staining and laser-assisted indocyanine green angiography using SPY Elite System were used for vascular territories assessment. The dissection of cadaver sheep heads confirmed that the hemifacial flap and auricle flap can be raised on the same pedicle consisting of the common carotid artery and jugular vein. An adequate vascular network was observed in the flaps after injection of methylene blue dye via the arterial pedicle. Laser-assisted indocyanine green angiography identified vascular territories of the hemifacial and auricular vascular network. We described a new hemifacial and an auricular transplantation models in the sheep cadavers and have confirmed presence of the adequate vascular network as demonstrated by the laser-assisted angiography. This study introduces 2 new large animal models into the armamentarium of vascular composite allotransplantation.
    No preview · Article · Apr 2014 · Annals of plastic surgery
  • Article: Abstract 90

    No preview · Article · Mar 2014 · Plastic & Reconstructive Surgery
  • Article: Abstract 64

    No preview · Article · Mar 2014 · Plastic & Reconstructive Surgery
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    ABSTRACT: Background: Venous grafting has been widely used in microsurgical training. Different types of vascular grafts have been described in experimental models. In this study we describe for the first time the Y- and X-shaped vein grafts (YVG, XVG) with accompanying drain-out branches as a new tool for the microsurgical training and free flap applications in rats. Methods: Twelve adult male Lewis rats were used in this study. The dissections were performed to determine the average diameter and harvestable length of vein grafts in eight rats. In four rats vein grafts were applied for bridging of the common carotid artery gap, whereas the drain-out branches were used as the arterial source for single and bilateral free groin flap applications. The venous anastomoses of groin flaps were performed in end-to-end fashion to the external jugular vein and its branches. The patency of anastomoses was checked 72 hours after repair. Results: The average length of the harvestable vein branches ranged between 5.2 to 11.8 mm. The average surgery time for repair of the arterial gap with the vein grafts was 40 minutes. The ischemia time for single and bilateral groin flap transfer using YVG and XVG was 30 and 70 minutes, respectively. The patency of the interpositional vein graft was 100%. Flap survival rates were 50%. Conclusions: These vein grafts can be used as an alternative technique for reconstruction of tissue defects that require arterial gap repair with single or multiple free flap applications and also as a new microsurgical training model.
    No preview · Article · Feb 2014 · Journal of Reconstructive Microsurgery

  • No preview · Conference Paper · Jan 2014

Publication Stats

5k Citations
686.27 Total Impact Points

Institutions

  • 2004-2015
    • University of Illinois at Chicago
      Chicago, Illinois, United States
  • 2000-2013
    • Cleveland Clinic
      • • Department of Plastic Surgery
      • • Department of Plastic and Reconstructive Surgery
      Cleveland, Ohio, United States
    • Universität zu Lübeck
      Lübeck Hansestadt, Schleswig-Holstein, Germany
  • 2007-2012
    • Case Western Reserve University
      Cleveland, Ohio, United States
    • American Society of Ophthalmic Plastic and Reconstructive Surgery
      Cleveland, Ohio, United States
    • Lerner Research Institute
      Cleveland, Ohio, United States
  • 2007-2008
    • Poznan University of Medical Sciences
      Posen, Greater Poland Voivodeship, Poland
  • 2002
    • Gazi University
      • Department of Plastic and Reconstructive Surgery
      Engüri, Ankara, Turkey
  • 1999
    • Salt Lake City Community College
      Salt Lake City, Utah, United States
  • 1993-1995
    • University of Utah
      • Division of Plastic Surgery
      Salt Lake City, Utah, United States