Mesenchymal stromal cells as treatment for acute respiratory distress syndrome. Case Reports following hematopoietic cell transplantation and a review

Abstract

Acute respiratory distress syndrome (ARDS) is a life-threatening lung disease. It may occur during the pancytopenia phase following allogeneic hematopoietic cell transplantation (HCT). ARDS is rare following HCT. Mesenchymal stromal cells (MSCs) have strong anti-inflammatory effect and first home to the lung following intravenous infusion. MSCs are safe to infuse and have almost no side effects. During the Covid-19 pandemic many patients died from ARDS. Subsequently MSCs were evaluated as a therapy for Covid-19 induced ARDS. We report three patients, who were treated with MSCs for ARDS following HCT. Two were treated with MSCs derived from the bone marrow (BM). The third patient was treated with MSCs obtained from the placenta, so-called decidua stromal cells (DSCs). In the first patient, the pulmonary infiltrates cleared after infusion of BM-MSCs, but he died from multiorgan failure. The second patient treated with BM-MSCs died of aspergillus infection. The patient treated with DSCs had a dramatic response and survived. He is alive after 7 years with a Karnofsky score of 100%. We also reviewed experimental and clinical studies using MSCs or DSCs for ARDS. Several positive reports are using MSCs for sepsis and ARDS in experimental animals. In man, two prospective randomized placebo-controlled studies used adipose and BM-MSCs, respectively. No difference in outcome was seen compared to placebo. Some pilot studies used MSCs for Covid-19 ARDS. Positive results were achieved using umbilical cord and DSCs however, optimal source of MSCs remains to be elucidated using randomized trials.

Successful salvage of a severe COVID-19 patient previously with lung cancer and radiation pneumonitis by mesenchymal stem cells: a case report and literature review

“…In 2020, Chinese physicians successively shared several cases of severe pneumonia treated with MSCs ( 82 – 88 ), and then similar cases began to be reported in other countries and regions ( 87 – 96 ). The dose range for an intravenous drip of MSCs was ( 1 – 3 ) × 10 6 kg in most of the cases ( 82 – 90 , 96 ). It is also important to note that none of these cases had a history of cancer, except for three cases reported in Sweden in 2022 ( 96 ) ( Table 1 ).…”

“…The dose range for an intravenous drip of MSCs was ( 1 – 3 ) × 10 6 kg in most of the cases ( 82 – 90 , 96 ). It is also important to note that none of these cases had a history of cancer, except for three cases reported in Sweden in 2022 ( 96 ) ( Table 1 ).…”

“…MSCs have been tried as a salvage treatment for critically ill pneumonia patients after the outbreak of the pandemic. In 2020, Chinese physicians successively shared several cases of severe pneumonia treated with MSCs (82-88), and then similar cases began to be reported in other countries and regions (87)(88)(89)(90)(91)(92)(93)(94)(95)(96). The dose range for an intravenous drip of MSCs was (1-3) × 10 6 kg in most of the cases (82)(83)(84)(85)(86)(87)(88)(89)(90)96).…”

Novel therapies for graft versus host disease with a focus on cell therapies

“…Three cases of ARDS, a rare side effect of HCT, have been treated with MSCs. Two patients given BM-MSCs did not survive, although the third patient who received DSCs, showed a dramatic response, and has survived seven years post-treatment thus far ( 176 ). DSC therapy was also recently shown to be safe and capable of improving oxygenation, decreasing inflammatory cytokine levels, and clearing pulmonary infiltrates in patients with COVID‐19 ( 172 ).…”

Effect and safety of mesenchymal stem cells for patients with COVID‐19: Systematic review and meta‐analysis with trial sequential analysis

“…16 MSCs are not brandnew therapy in the treatments of pulmonary diseases. Previous studies have demonstrated that patients with chronic obstructive pulmonary disease, 16 ARDS 17 or pulmonary fibrosis 18,19 could benefit from MSCbased therapy which reduces the inflammation and pulmonary tissue damage, improves the respiratory function, pulmonary microenvironment and reduces the mortality. At the same time, the anti-infammatory and immunomodulatory characteristics of MSC-based therapy make them as ideal candidates for the treatment of patients with acute and chronic inflammatory lung diseases.…”