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Review
. 2021 Oct;23(10):861-873.
doi: 10.1016/j.jcyt.2021.04.004. Epub 2021 Apr 30.

Mesenchymal stromal cell therapy for coronavirus disease 2019: which? when? and how much?

Pradnya Shahani  1 , Indrani Datta  2
Affiliations
Review

Mesenchymal stromal cell therapy for coronavirus disease 2019: which? when? and how much?

Pradnya Shahani et al. Cytotherapy. 2021 Oct.

Abstract

Mesenchymal stromal cells (MSCs) are under active consideration as a treatment strategy for controlling the hyper-inflammation and slow disease progression associated with coronavirus disease 2019 (COVID-19). The possible mechanism of protection through their immunoregulatory and paracrine action has been reviewed extensively. However, the importance of process control in achieving consistent cell quality, maximum safety and efficacy-for which the three key questions are which, when and how much-remains unaddressed. Any commonality, if it exists, in ongoing clinical trials has yet to be analyzed and reviewed. In this review, the authors have therefore compiled study design data from ongoing clinical trials to address the key questions of "which" with regard to tissue source, donor profile, isolation technique, culture conditions, long-term culture and cryopreservation of MSCs; "when" with regard to defining the transplantation window by identifying and staging patients based on their pro-inflammatory profile; and "how much" with regard to the number of cells in a single administration, number of doses and route of transplantation. To homogenize MSC therapy for COVID-19 on a global scale and to make it readily available in large numbers, a shared understanding and uniform agreement with respect to these fundamental issues are essential.

Keywords: CD142; MSC dosage; SARS-CoV-2; cytokine storm; hyper-coagulopathy; immunomodulation.

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Figures

Image, graphical abstract
Graphical abstract
Fig 1
Figure 1
Immunomodulatory and regenerative effects of MSCs. MSCs assert their immunomodulatory functions by directly or indirectly interacting with innate and adaptive immune cells and via paracrine secretion of cytokines, chemokines and growth factors. Their regenerative effects are attributed to homing to sites of inflammation; release of growth factors, exosomes, EVs and MVs; and direct mitochondrial donation to affected cells. Figure was prepared using BioRender (https://biorender.com/). BDNF, brain-derived neurotrophic factor; Breg, regulatory B cell; CNTF, ciliary neurotrophic factor; EVs, extracellular vesicles; MVs, microvesicles; NGF, nerve growth factor; NK, natural killer; NO, nitric oxide. (Color version of figure is available online).
Fig 2
Figure 2
(A) Various tissue sources of MSCs in current COVID-19 clinical trials. MSCs from umbilical cord, adipose tissue and bone marrow appear to be the predominant MSC tissue sources. (B) Number of MSC doses employed in current COVID-19 clinical trials. One and three doses of MSC infusions are most commonly employed in ongoing trials. Five doses is the highest number of doses observed. Figure data taken from https://clinicaltrials.gov/. (Color version of figure is available online).
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