scholarly journals Immunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructs

2021 ◽  
Vol 8 ◽  
Author(s):  
Danielle Wu ◽  
Isabelle M. A. Lombaert ◽  
Maximilien DeLeon ◽  
Swati Pradhan-Bhatt ◽  
Robert L Witt ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Parotid Gland ◽  
Transplant Rejection ◽  
Surgical Techniques ◽  
Da Vinci Surgical System ◽  
Large Animal ◽  
Host Animal ◽  
Cell Therapies ◽  
Kidney Capsule ◽  
Large Animal Models

An urgent need exists to develop large animal models for preclinical testing of new cell therapies designed to replace lost or damaged tissues. Patients receiving irradiation for treatment of head and neck cancers frequently develop xerostomia/dry mouth, a condition that could one day be treated by cell therapy to repopulate functional saliva-producing cells. Using immunosuppression protocols developed for patients receiving whole face transplants, we successfully used immunosuppressed miniswine as a suitable host animal to evaluate the long-term stability, biocompatibility, and fate of matrix-modified hyaluronate (HA) hydrogel/bioscaffold materials containing encapsulated salivary human stem/progenitor cells (hS/PCs). An initial biocompatibility test was conducted in parotids of untreated miniswine. Subsequent experiments using hS/PC-laden hydrogels were performed in animals, beginning an immunosuppression regimen on the day of surgery. Implant sites included the kidney capsule for viability testing and the parotid gland for biointegration time periods up to eight weeks. No transplant rejection was seen in any animal assessed by analysis of the tissues near the site of the implants. First-generation implants containing only cells in hydrogel proved difficult to handle in the surgical suite and were modified to adhere to a porcine small intestinal submucosa (SIS) membrane for improved handling and could be delivered through the da Vinci surgical system. Several different surgical techniques were assessed using the second-generation 3D-salivary tissue (3D-ST) for ease and stability both on the kidney capsule and in the capsule-less parotid gland. For the kidney, sliding the implant under the capsule membrane and quick stitching proved superior to other methods. For the parotid gland, creation of a tissue “pocket” for placement and immediate multilayer tissue closure were well tolerated with minimal tissue damage. Surgical clips were placed as fiduciary markers for tissue harvest. Some implant experiments were conducted with miniswine 90 days post-irradiation when salivation decreased significantly. Sufficient parotid tissue remained to allow implant placement, and animals tolerated immunosuppression. In all experiments, viability of implanted hS/PCs was high with clear signs of both vascular and nervous system integration in the parotid implants. We thus conclude that the immunosuppressed miniswine is a high-value emerging model for testing human implants prior to first-in-human trials.

scholarly journals Large Animal Models for Investigating Cell Therapies of Stress Urinary Incontinence

2021 ◽  
Vol 22 (11) ◽  
pp. 6092
Author(s):  
Bastian Amend ◽  
Niklas Harland ◽  
Jasmin Knoll ◽  
Arnulf Stenzl ◽  
Wilhelm K. Aicher
Keyword(s):  
Urinary Incontinence ◽  
Stress Urinary Incontinence ◽  
Animal Models ◽  
Clinical Situation ◽  
Surgical Instruments ◽  
Health Concern ◽  
Large Animal ◽  
Knock Out ◽  
Cell Therapies ◽  
Large Animal Models

Stress urinary incontinence (SUI) is a significant health concern for patients affected, impacting their quality of life severely. To investigate mechanisms contributing to SUI different animal models were developed. Incontinence was induced under defined conditions to explore the pathomechanisms involved, spontaneous recovery, or efficacy of therapies over time. The animal models were coined to mimic known SUI risk factors such as childbirth or surgical injury. However, animal models neither reflect the human situation completely nor the multiple mechanisms that ultimately contribute to the pathogenesis of SUI. In the past, most SUI animal studies took advantage of rodents or rabbits. Recent models present for instance transgenic rats developing severe obesity, to investigate metabolic interrelations between the disorder and incontinence. Using recombinant gene technologies, such as transgenic, gene knock-out or CRISPR-Cas animals may narrow the gap between the model and the clinical situation of patients. However, to investigate surgical regimens or cell therapies to improve or even cure SUI, large animal models such as pig, goat, dog and others provide several advantages. Among them, standard surgical instruments can be employed for minimally invasive transurethral diagnoses and therapies. We, therefore, focus in this review on large animal models of SUI.

scholarly journals In vivo cerebral aneurysm models

2019 ◽  
Vol 47 (1) ◽  
pp. E20 ◽  
Author(s):  
John W. Thompson ◽  
Omar Elwardany ◽  
David J. McCarthy ◽  
Dallas L. Sheinberg ◽  
Carlos M. Alvarez ◽  
...  
Keyword(s):  
Cerebral Aneurysm ◽  
Surgical Techniques ◽  
Cerebral Aneurysms ◽  
Aneurysm Rupture ◽  
Large Animal ◽  
Pharmacological Interventions ◽  
Large Animal Models ◽  
First Line Therapy ◽  
Endovascular Devices

Cerebral aneurysm rupture is a devastating event resulting in subarachnoid hemorrhage and is associated with significant morbidity and death. Up to 50% of individuals do not survive aneurysm rupture, with the majority of survivors suffering some degree of neurological deficit. Therefore, prior to aneurysm rupture, a large number of diagnosed patients are treated either microsurgically via clipping or endovascularly to prevent aneurysm filling. With the advancement of endovascular surgical techniques and devices, endovascular treatment of cerebral aneurysms is becoming the first-line therapy at many hospitals. Despite this fact, a large number of endovascularly treated patients will have aneurysm recanalization and progression and will require retreatment. The lack of approved pharmacological interventions for cerebral aneurysms and the need for retreatment have led to a growing interest in understanding the molecular, cellular, and physiological determinants of cerebral aneurysm pathogenesis, maturation, and rupture. To this end, the use of animal cerebral aneurysm models has contributed significantly to our current understanding of cerebral aneurysm biology and to the development of and training in endovascular devices. This review summarizes the small and large animal models of cerebral aneurysm that are being used to explore the pathophysiology of cerebral aneurysms, as well as the development of novel endovascular devices for aneurysm treatment.

scholarly journals Large animal models for cardiac stem cell therapies

2011 ◽  
Vol 75 (8) ◽  
pp. 1416-1425 ◽  
Author(s):  
F. Gandolfi ◽  
A. Vanelli ◽  
G. Pennarossa ◽  
M. Rahaman ◽  
F. Acocella ◽  
...  
Keyword(s):  
Stem Cell ◽  
Animal Models ◽  
Large Animal ◽  
Cardiac Stem Cell ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Large Animal Models

scholarly journals Evolution of the rat hind limb transplant as an experimental model of vascularized composite allotransplantation: Approaches and advantages

2020 ◽  
Vol 8 ◽  
pp. 205031212096872
Author(s):  
Yoram Y Fleissig ◽  
Jason E Beare ◽  
Amanda J LeBlanc ◽  
Christina L Kaufman
Keyword(s):  
Upper Extremity ◽  
Hind Limb ◽  
Large Body ◽  
Surgical Techniques ◽  
Experimental Models ◽  
Tissue Loss ◽  
Large Animal ◽  
Solid Organ ◽  
Vascularized Composite Allotransplantation ◽  
Large Animal Models

As clinical experience with surgical techniques and immunosuppression in vascularized composite allotransplantation recipients has accumulated, vascularized composite allotransplantation for hand and face have become standard of care in some countries for select patients who have experienced catastrophic tissue loss. Experience to date suggests that clinical vascularized composite allotransplantation grafts undergo the same processes of allograft rejection as solid organ grafts. Nonetheless, there are some distinct differences, especially with respect to the immunologic influence of the skin and how the graft is affected by environmental and traumatic insults. Understanding the mechanisms around these similarities and differences has the potential to not only improve vascularized composite allotransplantation outcomes but also outcomes for all types of transplants and to contribute to our understanding of how complex systems of immunity and function work together. A distinct disadvantage in the study of upper extremity vascularized composite allotransplantation recipients is the low number of clinical transplants performed each year. As upper extremity transplantation is a quality of life rather than a lifesaving transplant, these numbers are not likely to increase significantly until the risks of systemic immunosuppression can be reduced. As such, experimental models of vascularized composite allotransplantation are essential to test hypotheses regarding unique characteristics of graft rejection and acceptance of vascularized composite allotransplantation allografts. Rat hind limb vascularized composite allotransplantation models have been widely used to address these questions and provide essential proof-of-concept findings which can then be extended to other experimental models, including mice and large animal models, as new concepts are translated to the clinic. Here, we review the large body of rat hind limb vascularized composite allotransplantation models in the literature, with a focus on the various surgical models that have been developed, contrasting the characteristics of the specific model and how they have been applied. We hope that this review will assist other researchers in choosing the most appropriate rat hind limb transplantation model for their scientific interests.

scholarly journals Harvest and Culture of Porcine Adipose-Derived Mesenchymal Stem Cells for Autologous Transplantation

2020 ◽  
Author(s):  
Ayushman Sharma ◽  
Allan B. Dietz
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Autologous Transplantation ◽  
Large Animal Model ◽  
Large Animal ◽  
Cell Therapies ◽  
Large Animal Models ◽  
Human Adscs ◽  
Regulatory Submissions ◽  
Laboratory Procedures

AbstractImportanceTransplantation of adipose-derived (mesenchymal) stem cells (ADSCs) are currently under investigation for numerous novel regenerative cell therapies of the head, neck and periphery. Critical to the development of these techniques is the availability of large-animal models that can be used to test the safety and efficacy of these approaches in a manner that provides source material (in this case MSC) analogous to those developed in humans.ObjectiveTo describe the surgical technique and laboratory procedures for harvesting and isolating porcine ADSCs that are functionally equivalent to human ADSCs without sacrificing the donor animal.MethodsThe reagents and methods used in the porcine model described were purposefully focused to be able to be sufficiently analogous to those used in humans such that data developed using these techniques should support the use of porcine models for regulatory submissions.ResultsWe describe a method and confirm the activity of functionally analogous adipose derived porcine MSC. Two conditions were critical to move gain analogous performance: the cells needed to be incubated at porcine body temperature (39°C) and the cells were more sensitive to initial plating densities with plating densities of 20,000 cells/cm2 being optimal.DiscussionThis approach will allow reproducible and predictable use of an autologous large-animal model for testing AMDSC therapies.

scholarly journals Flap Surgical Techniques For Incisional Hernias Reccurences. A Swine Experimental Model

2017 ◽  
Vol 90 (2) ◽  
pp. 203-211
Author(s):  
Florina Popa ◽  
Filip Ardelean ◽  
Cosmin Pestean ◽  
Robert Purdoiu ◽  
Oana Rosca ◽  
...  
Keyword(s):  
Abdominal Wall ◽  
Mesh Repair ◽  
Surgical Techniques ◽  
Careful Examination ◽  
Large Animal ◽  
Abdominal Wall Defects ◽  
Flap Surgery ◽  
Abdominal Wall Repair ◽  
Large Animal Models ◽  
The University

Background and aims. In the age of synthetic prostheses most of hernia studies include a careful examination of the various types of prosthesis, their characteristics and their repair indications. Biological prostheses are also beginning to draw attention. But in terms of recurrence especially for poor or developing countries, the discussion is different, due to their high cost which makes them difficult to afford. In this article we present new flap reconstruction techniques for the reconstruction of the abdominal wall versus mesh repair, applied on swine models, outline the results of each technique, and specify the indications for their use.Methods. An experimental protocol using four swine models (PIC-FII-337 hybrid breed pigs), five months old, was conducted. All animal care and operative procedures were studied following the protocol approved by the Ethics Committee of the University of Medicine and Pharmacy resolution no. 281/2014 of the Department of Surgery of the University of Agricultural Sciences and Veterinary Medicine); the study was carried out between November 2015 and February 2016. The primary objective was to compare the effect of surgical strategies in the treatment of the abdominal wall defect using variable flaps versus mesh repair in a large-animal models. Physical examination and ultrasound imaging of the abdominal wall repair were done on determined periods, during one month. The complications occurring after the abdominal wall repair were edema, collections, superficial dehiscence an recurrences.Results. No recurrences were reported at one month results, all seromas reported were solved over time by natural drainage. Superficial necrosis appeared in two swine models and superficial dehiscence occurred in one model, the perforator ”plus” flap. Mesh infection was detected in the “onlay” swine model.Conclusions. In terms of recurrences, contaminated abdominal wall defects or other contraindications to the use of prosthetic materials, biological mesh repair or flap surgery are the only surgical options. Based on our findings and considering the high cost reported by the biological meshes use, flap surgery becomes the suitable treatment for such cases, allowing a good reconstruction of the abdominal wall.

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