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Background: Mesenchymal stem cells (MSCs) are multipotent cells that demonstrate therapeutic potential for the treatment of acute and chronic inflammatory-mediated conditions. Although controversial, some studies suggest that MSCs may lose their functionality with cryopreservation which could render them non-efficacious.Objective: In comparative pre-clinical models of inflammation, to determine if there are differences in in-vivo measures of pre-clinical efficacy (primary outcomes) and in-vitro potency (secondary outcomes) between freshly-cultured and cryopreserved MSCs. Methods: A systematic search on OvidMEDLINE, EMBASE, BIOSIS, and Web of Science (until June 5, 2020) was conducted. The primary outcome included measures of in-vivo pre-clinical efficacy; secondary outcomes included measures of in-vitro MSC potency. Risk of bias was assessed by the SYRCLE “Risk of Bias” assessment tool for pre-clinical studies. Results: 15 studies were included. A total of 194 in-vivo pre-clinical efficacy experiments represented 72 distinct outcome measures. 2.6% (5/194) of these outcomes were significantly different at the 0.05 level or less; 2 favoured freshly-cultured and 3 favoured cryopreserved MSCs. A total of 63 in-vitro experiments represented 26 different potency measures; 11.1% (7/63) of the experiments were significantly different at the 0.05 level or less, with 5 experiments favouring freshly-cultured MSC and 2 favouring cryopreserved MSCs.Conclusions: The majority of preclinical in-vivo outcomes and in-vitro potency outcomes did not detect significant differences (pRegistration: Protocol has been registered with PROSPERO (CRD42020145833).

Mesenchymal stem cells (MSCs) are being studied for the treatment of COVID-19-associated critical illness, due to their immunomodulatory properties. Here, we hypothesized that viral mimic-priming improves MSCs' abilities to rebalance the dysregulated immune responses in COVID-19. Transcriptome analysis of poly(I:C)-primed MSCs (pIC-MSCs) showed upregulation of pathways in antiviral and immunomodulatory responses. Together with increased expression of antiviral proteins such as MX1, IFITM3, and OAS1, these changes translated to greater effector functions in regulating monocytes and granulocytes while further enhancing MSCs' ability to block SARS-CoV-2 pseudovirus entry into epithelial cells. Most importantly, the addition of pIC-MSCs to COVID-19 patient whole blood significantly reduced inflammatory neutrophils and increased M2 monocytes while enhancing their phagocytic effector function. We reveal for the first time that MSCs can be primed by Toll-like receptor 3 agonist to improve their ability to rebalance the dysregulated immune responses seen in severe SARS-CoV-2 infection.

Supplemental material, PUL883613 Supplemetal Material for Optimizing imaging of the rat pulmonary microvasculature by micro-computed tomography by Yupu Deng, Katelynn J. Rowe, Ketul R. Chaudhary, Anli Yang, Shirley H.J. Mei and Duncan J. Stewart in Pulmonary Circulation

Supplemental material, PUL883613 Supplemetal Material for Optimizing imaging of the rat pulmonary microvasculature by micro-computed tomography by Yupu Deng, Katelynn J. Rowe, Ketul R. Chaudhary, Anli Yang, Shirley H.J. Mei and Duncan J. Stewart in Pulmonary Circulation