Mesenchymal stem cells and management of COVID-19 pneumonia

Abstract

Human coronavirus, hCoV-19, is highly pathogenic with severe pneumonia associated with rapid virus replication. Arising in Wuhan China December 2019, the current COVID-19 epidemic has rapidly grown with person-to-person infection expanding to become a global health emergency now on pandemic scale. Governments will not be able to minimise both deaths from COVID-19 and the economic impact of viral spread in mitigation of this current COVID-19 pandemic, according to Anderson et al. 2020 [1], Keeping mortality as low as possible will be the highest priority for individuals; hence governments must put in place measures to ameliorate the inevitable economic downturn. The current global picture shows small chains of transmission in many countries and large chains resulting in extensive spread in a few countries, such as Italy, Iran, South Korea, and Japan. Most countries are likely to have spread of COVID-19, at least in the early stages, before any mitigation measures have an impact. The scale of the problem is massive. Here I consider new approaches to improve patient's biological resistance to COVID-19 using stem cells, and how benefit might be scaled and simplified using synthetic stem cells to meet logistical needs within a short time frame.

Keywords: Corona virus; Cytokine storm; Leukaemia inhibitory factor; Mesenchymal stem cells; Synthetic stem cells.

Fig. 1

Influence of endogenous LIF on responses to infection. Adapted from Quinton et al. [6]. Previous Studies had shown that LIF is particularly important for the epithelial STAT3 activating capacity of pneumonic alveolar lining, and that treatment with exogenous LIF [9] or LIF over-expression [10] can limit pulmonary inflammation in response to LPS or hyperoxia. The Quinton experiment illustrated here investigates the requirement for endogenous LIF to protect against acute lung injury. Lungs were collected from mice 24 h after intratracheal inoculation of Escherichia coli co-instilled with anti-LIF or control IgG. (A): Representative images of intact freshly isolated lungs and hematoxylin/eosin-stained lung sections. Red circles denote infected left lung lobes. (B) Lung wet:dry weight ratios show effect of anti-LIF treatment expressed as means ± SEM. *p < 0.05 compared to mice treated with control IgG (n = 3–5). The anti-LIF resulted in LIF being undetectable, whilst the other cytokines measured - GCSF, GM-CSF, IL-10, IL-17, IL-1β, IL-6, KC, MIP-2 - were not significantly altered by the anti-LIF treatment. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2

Paralysis in an EAE model is rapidly reversed by LIFNano therapy. C57/Bl10 mice were immunised against myelin protein (MOG) resulting in paralysis of hind limbs and tail by day 14: protocol was the Hooke model of experimental allergic encephalopathy - this provides a standardised preclinical animal model of Multiple Sclerosis. Untreated: Mice 15 days post immunisation showing paralysis of hind limbs and tail. Treated: Mice treated identically and showing paralysis at 15d, then followed by 4 days treatment with 1 mg/day i.p. LIFNano-CD4 nanoparticles. There is a significant recovery of movement: this improved further with prolonged therapy. The results are highly reproducible, and control nanoparticles without LIF cargo targeted to CD4 had no effect on paralysis. (This study was part of an I-UK BMC Project “CELL-FREE REGENERATIVE MEDICINE: Nano-Engineered “LIFNano” to treat Multiple Sclerosis” PROJECT NUMBER: 102847).