Page 88 - Human Umbilical Cord Mesenchymal Stem Cells

Shu et al. Stem Cell Research & Therapy (2020) 11:361 Page 2 of 11

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Trial registration: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http://www.
medresman.org
Keywords: Coronavirus disease-19 (COVID-19), Clinical characteristics, Coronavirus pneumonia, Human umbilical
cord mesenchymal stem cells

Introduction the treatment of severe COVID-19. To date, the safety
In December 2019, a series of pneumonia cases occurred and therapeutic effect of hUC-MSCs on severe COVID-
in Wuhan City, Hubei Province, and other parts of 19 have not been reported.
China [1]. Recently, the causative agent was identified as To evaluate the efficacy of hUC-MSCs for treating se-
a novel coronavirus, designated SARS-CoV-2 [2, 3], and vere COVID-19, we conducted this hUC-MSC transplant-
this type of pneumonia was named coronavirus disease ation pilot study to elucidate the potential therapeutic role
2019 (COVID-19). Since then, the number of COVID-19 of these cells in the treatment of severe COVID-19.
patients has sharply increased not only in China but also
in most of the world. By April 5, 2020, there were more
Methods
than 1,000,000 confirmed COVID-19 patients and more
Study design and participants
than 57,000 deaths in 207 countries, areas, or territories
This study was a single-center open-label, individually
all over the world [4]. According to data from the
randomized, standard treatment-controlled trial con-
WHO, the mortality of COVID-19 is 5.17%; in some
ducted at Huangshi Hospital of Traditional Chinese
places, however, the mortality rate is higher, reaching
Medicine in Hubei Province from Feb 12 to March 25,
16.7% [5], which depends on the sample size included
2020, and it was performed according to the Declaration
and the severity of the outbreak. Therefore, controlling
of Helsinki and approved by the Ethics Committee of
the mortality rate of critically ill patients is of paramount
the Huangshi Hospital of Traditional Chinese Medicine
importance. Considering its high prevalence and infec-
(No. HSZYPJ-2020-009-01). Written informed consent
tion rates, the World Health Organization (WHO) has
was obtained from all patients or their representatives
declared COVID-19 a pandemic [6], and it has grown to
when data were collected retrospectively.
be a public health emergency of international concern
The diagnosis of COVID-19 was based on WHO in-
that represents an enormous threat to global health.
terim guidance [19] and a new coronavirus pneumonia
However, thus far, no specific drugs or vaccines are
diagnosis and treatment program (6th ed.) (in Chinese)
available to treat COVID-19 patients.
[20]; the criteria for severe disease are (A) an epidemio-
Recently, studies have found that SARS-COV-2 inter-
logical history; (B) etiological evidence (i.e., a positive
acts with human mucosal epithelial cells through ACE2
SARS-CoV-2 nucleic acid test by the real-time reverse
in a manner dependent on both binding of the viral
transcription polymerase chain reaction (RT-PCR) assay
spike (S) proteins to cellular receptors and S protein
for SARS-CoV-2 RNA from the Chinese Center for Dis-
priming by host cell proteases [7, 8], which reveals cellu-
ease Control and Prevention following the protocol de-
lar factors that may be used as therapeutic targets for
scribed previously [11, 21]); and (C) CT imaging
controlling SARS-CoV-2 transmission.
indicators of pneumonia. In addition, these factors
Mesenchymal stem cells (MSCs) have been widely used
should coincide with any of the following criteria: (a) re-
in the clinical setting, not only for autoimmune diseases
spiratory distress, respiration rate (RR) ≥ 30 times/min;
[9, 10] but also for infectious diseases [11–13], and their
(b) oxygen saturation ≤ 93% in the resting state; and (c)
safety and effectiveness have been well elucidated. Umbil-
PaO 2 /FiO 2 ≤ 300 mmHg (1 mmHg = 0.133 kPa). In gen-
ical cord mesenchymal stem cells (hUC-MSCs), a kind of
eral, patients with severe COVID-19 whose clinical
MSC, can be easily obtained and expanded in vitro.
symptoms were not significantly alleviated under stand-
Numerous studies have shown that hUC-MSCs have
ard treatment for 7 to 10 days were recommended for
significant immune modulation and tissue repair func-
participation in this pilot study. The patients were ran-
tions due to their low immunogenicity [14–16]. As an
domly divided into 2 groups: a standard treatment group
ideal candidate for allogenic adoptive transfer therapy,
(control group) and a standard treatment plus umbilical
hUC-MSCs have been shown to play a protective role in
cord mesenchymal stem cell infusion group (hUC-MSC
A/H5N1-associated acute lung injury [17]. Although one
group). The standard treatment was as follows: (1) sup-
article has been published recently on the therapeutic ef-
plemental oxygen (noninvasive or invasive ventilation),
fects of stem cells on COVID-19, it was about bone mar-
(2) antiviral agents (abidor/oseltamivir), (3) antibiotic
row mesenchymal stem cells [18] and did not focus on
agents (moxifloxacin is taken orally; if there is clear