Page 98 - Mesenchymal Stem cells, Exosomes and vitamins in the fight aginst COVID

Intravascular Mesenchymal Stem Cells to Treat Organ Failure and Possible Application in COVID-19

Kidney Failure cells in treating COVID-19 patients, there have been
Kidney disease can be either acute or chronic, very few published clinical trials. In the first reported
which can lead to decline in function and ultimately study, 7 patients who were severely affected by
organ failure. Acute kidney injury is characterized by COVID-19 and not responding to conventional treat-
rapid loss of function and can occur from renal isch- ment were treated with an IV dose of 1 million/kg
emia, crush injury, inflammation, or infection, whereas cultured umbilical cord stem cells and compared with
chronic kidney disease (CKD) is characterized by pro- 3 patients in the control group receiving traditional
gressive loss of kidney function leading to end-stage treatment (40). Approximately 2 to 4 days after MSC
renal disease. Many diseases and conditions, such as treatment, patients had significant recovery with ma-
diabetes, polycystic kidney disease, autoimmune con- jor resolution of the pulmonary computed tomogra-
ditions, interstitial nephritis, recurrent infections, and phy changes. Other organs apart from the lung were
others, can lead to CKD. This is a significant global also involved in the patients of this trial. Biochemical
public health problem causing significant morbidity indicators in the blood test showed that aspartic
and mortality. aminotransferase, creatine kinase activity, and myo-
Numerous studies have investigated the feasibility, globin increased sharply, indicating severe damage to
safety, and efficacy of MSC-based therapies for kidney the liver and myocardium and decreased glomerular
disease, which are described in Table 5. We looked at filtration rate (GFR), which reflected kidney failure.
human clinical trials assessing the effect of MSCs in vari- However, the levels of these functional biochemical
ous conditions causing kidney disease. We found a total indicators were decreased to normal reference values
of 9 studies (5 case series, 3 RCTs, and 1 pragmatic clini- in 2 to 4 days after MSC treatment. The decrease in
cal trial). Among these, 3 trials were on lupus nephritis GFR also normalized after the infusion. All patients
, one on idiopathic membranous nephropathy, one RCT in the treatment arm recovered. However, in the
on diabetic nephropathy , one on renal vascular disease control group, one patient died, whereas one patient
, and one RCT on acute kidney injury after cardiac sur- developed ARDS, and the third patient recovered. No
gery . There are 2 case series, one on polycystic kidney complications from MSC infusion were reported.
disease and one on CKD. Most of the studies used bone The second trial infused exosomes into 24 critical
marrow MSCs, whereas 2 studies used human umbilical patients with COVID-19 who had moderate to severe
cord MSCs, and one study used adipose-derived MSC. ARDS (65). Significant improvements in oxygenation,
Mesenchymal stromal cells were administered intrave- neutrophil/lymphocyte counts, D-dimer, ferritin, and
nously in 7 trials, whereas they were given intraaortic C-reactive protein were seen; 71% of patients recov-
in one study, and via intrarenal artery in one study. Out ered, 13% remained critically ill, and 16% died. No
of the 9 studies, only 3 studies had favorable outcomes adverse reactions from the treatment were reported.
(bone marrow mononuclear cells were used in only one A case report of a 65-year-old woman diagnosed
of these trials). Two of these trials treated lupus nephri- with COVID-19 was admitted as she was worsening
tis and one treated patient with renovascular disease. symptomatically. She continued to deteriorate for the
Both the lupus studies showed improvement in SLEDAI next 9 days with decreasing oxygen saturation coin-
(systemic lupus erythematosus disease activity index) ciding with ground glass appearance on the x-ray and
scores, British Isles Lupus Assessment Group scores, and computed tomography scan. She also developed gas-
glomerular filtration rate. One of these studies also re- trorrhea and anemia necessitating blood transfusion.
ported 60.5% partial or complete remission resulting in Elevated bilirubin and ALT/AST indicated liver failure.
tapering the doses of the prednisone and immunosup- Because she was not responding to conventional
pressive drugs. Cortical perfusion and renal blood flow treatment, including steroids, antivirals, antibiotics,
improved in the renal vascular disease study. The rest and immunoglobulins, 3 doses of 50 million umbilical
of the studies failed to show any improvement in renal cord (UC) MSCs were infused 3 days apart. After the
function. No complications were noted. second dose, her liver and blood indices normalized,
and she was eventually taken off the ventilator 5
Clinical Trials for Biologics to Treat days later. The patient was discharged from the ICU
Seriously Ill COVID-19 Patients after 9 days (66).
Although there are numerous media reports There were 17 patients with ARDS from influ-
purporting the success of parenteral expanded stem enza A (H7N9) who were treated with 3 to 4 IV doses

www.painphysicianjournal.com S415