Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Oct;16(5):812-827.
doi: 10.1007/s12015-020-10000-1.

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  5   6
Affiliations
Review

Genetically Modified Mesenchymal Stromal/Stem Cells: Application in Critical Illness

Amir K Varkouhi et al. Stem Cell Rev Rep. 2020 Oct.

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: Critical illness; Gene therapy; Mesenchymal stromal/stem cells; Vector.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Umegaki, T., Ikai, H., & Imanaka, Y. (2011, 27). The impact of acute organ dysfunction on patients’ mortality with severe sepsis. Journal of Anaesthesiology Clinical Pharmacology, (2), 180–184. 10.4103/0970-9185.81816 PubMed PMID: 21772676; PubMed Central PMCID: PMCPMC3127295. - PMC - PubMed
    1. Terblanche M, Kruger P, di Gangi S, Gearay S, Gilfeather L, Ferguson ND, et al. Risk factors for acute organ failure in intensive care unit patients who receive respiratory support in the absence of non-respiratory organ failure: An international prospective cohort study. Critical Care. 2012;16(2):R61. doi: 10.1186/cc11306. - DOI - PMC - PubMed
    1. Kaneki M. Metabolic inflammatory complex in sepsis: Septic cachexia as a novel potential therapeutic target. Shock. 2017;48(6):600–609. doi: 10.1097/SHK.0000000000000906. - DOI - PMC - PubMed
    1. Rossaint J, Zarbock A. Pathogenesis of multiple organ failure in sepsis. Critical Reviews in Immunology. 2015;35(4):277–291. doi: 10.1615/CritRevImmunol.2015015461. - DOI - PubMed
    1. Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, et al. Developing a new definition and assessing new clinical criteria for septic shock: For the third International consensus definitions for sepsis and septic shock (sepsis-3) JAMA. 2016;315(8):775–787. doi: 10.1001/jama.2016.0289. - DOI - PMC - PubMed