Genetically Modified Mesenchymal Stromal/Stem Cells: Application in Critical Illness
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REVIEW
Genetically Modified Mesenchymal Stromal/Stem Cells: Application in Critical Illness Amir K. Varkouhi 1 & Ana Paula Teixeira Monteiro 2,3 & James N. Tsoporis 2 & Shirley H. J. Mei 4 & Duncan J. Stewart 4 & Claudia C. dos Santos 2,5
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Critical illnesses including sepsis, acute respiratory distress syndromes, ischemic cardiovascular disorders and acute organ injuries are associated with high mortality, morbidity as well as significant health care system expenses. While these diverse conditions require different specific therapeutic approaches, mesenchymal stem/stromal cell (MSCs) are multipotent cells capable of self-renewal, tri-lineage differentiation with a broad range regenerative and immunomodulatory activities, making them attractive for the treatment of critical illness. The therapeutic effects of MSCs have been extensively investigated in several pre-clinical models of critical illness as well as in phase I and II clinical cell therapy trials with mixed results. Whilst these studies have demonstrated the therapeutic potential for MSC therapy in critical illness, optimization for clinical use is an ongoing challenge. MSCs can be readily genetically modified by application of different techniques and tools leading to overexpress or inhibit genes related to their immunomodulatory or regenerative functions. Here we will review recent approaches designed to enhance the therapeutic potential of MSCs with an emphasis on the technology used to generate genetically modified cells, target genes, target diseases and the implication of genetically modified MSCs in cell therapy for critical illness. Keywords Mesenchymal stromal/stem cells . Critical illness . Gene therapy . Vector
* Claudia C. dos Santos [email protected] 1
Department of Chemistry and Environmental Science, New Jersey Institute of Technology (NJIT), Newark, NJ 07102, USA
2
Keenan and Li Ka Shing Knowledge Institute, University Health Toronto – St. Michael’s Hospital, Toronto, Ontario, Canada
3
Institute of Medical Sciences and Department of Medicine, University of Toronto, Toronto, Ontario, Canada
4
Ottawa Hospital Research Institute and the University of Ottawa, Ottawa, ON, Canada
5
Interdepartmental Division of Critical Care, St. Michael’s Hospital/ University of Toronto, 30 Bond Street, Room 4-008, Toronto, ON M5B 1WB, Canada
Stem Cell Rev and Rep
Introduction Acute organ failure (AOF) can occur in patients with critical illnesses including severe infections, early sepsis and ischemic disorders necessitating admission to intensive care units (ICUs) [1, 2]. Sepsis can develop to more complex conditions leading to multiorgan dysfunction syndrome (MODS), which occurs as a response to pathophysiologic events and complicated interactions in body systems leading to immune, metabolic and hematologic dysfunctions [3, 4]. Sepsis associated with MODS is one of the leading causes of morbidity and mortality in ICUs worldwide [5]. In US, over 970,000 se
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