State of the Art Review of Cell Therapy in the Treatment of Lung Disease, and the Potential for Aerosol Delivery

Abstract

Respiratory and pulmonary diseases are among the leading causes of death globally. Despite tremendous advancements, there are no effective pharmacological therapies capable of curing diseases such as COPD (chronic obstructive pulmonary disease), ARDS (acute respiratory distress syndrome), and COVID-19. Novel and innovative therapies such as advanced therapy medicinal products (ATMPs) are still in early development. However, they have exhibited significant potential preclinically and clinically. There are several longitudinal studies published, primarily focusing on the use of cell therapies for respiratory diseases due to their anti-inflammatory and reparative properties, thereby hinting that they have the capability of reducing mortality and improving the quality of life for patients. The primary objective of this paper is to set out a state of the art review on the use of aerosolized MSCs and their potential to treat these incurable diseases. This review will examine selected respiratory and pulmonary diseases, present an overview of the therapeutic potential of cell therapy and finally provide insight into potential routes of administration, with a focus on aerosol-mediated ATMP delivery.

Compassionate mesenchymal stem cell treatment in a severe COVID-19 patient: a case report

“…MSC are pluripotent stem cells differentiating into different mesodermic and non-mesodermic lineages. Their se-cretome consists of immunomodulatory cytokines and chemokines, which were previously shown to modulate endothelial and epithelial permeability, promote endothelial repair, decrease scarring, and act anti-inflammatory (7). Autologous MSC are used in orthopedics for the treatment of osteoarthritis and have shown good results in pain reduction and increasing joint mobility, without any observed treatment-specific side effects (8)(9)(10).…”

Therapeutic Potential of Mesenchymal Stem Cells and Their Products in Lung Diseases—Intravenous Administration versus Inhalation

“…MSCs isolated from adipose tissue, autologous non-hematopoietic peripheral blood stem cells, not specified MSCs and specific T cells are indicated as exosome sources in these studies. More information on these trials is available in recent reviews and on ClinicalTrials.gov (accessed on 30 December 2020) (e.g., [1,72,126]). The small number of studies presently available does not allow identification of the number of inhaled MSCs to achieve optimum effects and of potential differences in the immune response to allogenic MSCs between intravenous and inhalation administration.…”

“…Since anesthesia is necessary, the intervention is not indicated for routine treatment [ 117 ]. Regarding uniformity of the distribution pattern, intratracheal administration is inferior to inhalation by spontaneously breathing patients [ 1 ].…”

“…Somatic cell therapy and tissue-engineered products belong to the advanced therapy medicinal products (ATMPs) [ 1 ]. Several products, Provenge ® , MACI ® , Chondrocelect ® , Zalmoxis ® , Alofisel ® , KTE-X19 ® , Holoclar ® and Spherox ® have obtained marketing authorization but Provenge ® , MACI ® , Chondrocelect ® and Zalmoxis ® already withdrew their product from the market [ 2 ].…”

Adipose-Derived Stem Cells Secretome and Its Potential Application in “Stem Cell-Free Therapy”

“…Acute respiratory distress syndrome is often observed in critically ill patients (~10% of all patients in intensive care units worldwide), and is most commonly associated with sepsis, pneumonia (bacterial and viral), severe trauma or aspiration of gastric, and/or oral and oesophageal contents [159]. Paracrine factors such as IFN-γ, IL-1β, IL-6, IL-10, TGF-β1, TGF-6, VEGF, HGF, PGE2, Ang-1, and IDO secreted by ASCs can attenuate lung injury [160]. Shigemura et al showed that HGF from ASCs can improve gas exchange thus treat pulmonary emphysema [161].…”