Pulmonary fibrosis significantly contributes to the pathogenesis of acute respiratory distress syndrome (ARDS), markedly increasing patient mortality. Despite the established anti-fibrotic effects of mesenchymal stem cells (MSCs), numerous challenges hinder their clinical application. A recent study demonstrated that microvesicles (MVs) from MSCs (MSC-MVs) could attenuate ARDS-related pulmonary fibrosis and enhance lung function via hepatocyte growth factor mRNA transcription. This discovery presents a promising strategy for managing ARDS-associated pulmonary fibrosis. This article initially examines the safety and efficacy of MSCs from both basic science and clinical perspectives, subsequently exploring the potential and obstacles of employing MSC-MVs as a novel therapeutic approach. Additionally, it provides perspectives on future research into the application of MSC-MVs in ARDS-associated pulmonary fibrosis.

Emphysema in patients with chronic obstructive pulmonary disease (COPD) is characterized by progressive inflammation. Preclinical studies suggest that lung volume reduction surgery (LVRS) and mesenchymal stromal cell (MSC) treatment dampen inflammation. We investigated the effects of bone marrow-derived MSC (BM-MSC) and LVRS on circulating and pulmonary immune cell profiles in emphysema patients using mass cytometry. Blood and resected lung tissue were collected at the first LVRS (L1). Following 6-10 weeks of recovery, patients received a placebo or intravenous administration of 2 × 106 cells/kg bodyweight BM-MSC (n = 5 and n = 9, resp.) in week 3 and 4 before the second LVRS (L2), where blood and lung tissue were collected. Irrespective of BM-MSC or placebo treatment, proportions of circulating lymphocytes including central memory CD4 regulatory, effector memory CD8 and γδ T cells were higher, whereas myeloid cell percentages were lower in L2 compared to L1. In resected lung tissue, proportions of Treg (p = 0.0067) and anti-inflammatory CD163- macrophages (p = 0.0001) were increased in L2 compared to L1, while proportions of pro-inflammatory CD163+ macrophages were decreased (p = 0.0004). There were no effects of BM-MSC treatment on immune profiles in emphysema patients. However, we observed alterations in the circulating and pulmonary immune cells upon LVRS, suggesting the induction of anti-inflammatory responses potentially needed for repair processes.

Advances in stem cell technology offer new possibilities for patients with untreated diseases and disorders. Stem cell-based therapy, which includes multipotent mesenchymal stem cells (MSCs), has recently become important in regenerative therapies. MSCs are multipotent progenitor cells that possess the ability to undergo in vitro self-renewal and differentiate into various mesenchymal lineages. MSCs have demonstrated promise in several areas, such as tissue regeneration, immunological modulation, anti-inflammatory qualities, and wound healing. Additionally, the development of specific guidelines and quality control methods that ultimately result in the therapeutic application of MSCs has been made easier by recent advancements in the study of MSC biology. This review discusses the latest clinical uses of MSCs obtained from the umbilical cord (UC), bone marrow (BM), or adipose tissue (AT) in treating various human diseases such as pulmonary dysfunctions, neurological disorders, endocrine/metabolic diseases, skin burns, cardiovascular conditions, and reproductive disorders. Additionally, this review offers comprehensive information regarding the clinical application of targeted therapies utilizing MSCs. It also presents and examines the concept of MSC tissue origin and its potential impact on the function of MSCs in downstream applications. The ultimate aim of this research is to facilitate translational research into clinical applications in regenerative therapies.

Chronic obstructive pulmonary disease (COPD) is considered a severe disease mitigating lung physiological functions with high mortality outcomes, insufficient therapy, and pathophysiology pathways which is still not fully understood. Mesenchymal stem cells (MSCs) derived from bone marrow play an important role in improving the function of organs suffering inflammation, oxidative stress, and immune reaction. It might also play a role in regenerative medicine, but that is still questionable. Additionally, Melatonin with its known antioxidative and anti-inflammatory impact is attracting attention nowadays as a useful treatment. We hypothesized that Melatonin may augment the effect of MSCs at the level of angiogenesis in COPD. In our study, the COPD model was established using cigarette smoking and lipopolysaccharide. The COPD rats were divided into four groups: COPD group, Melatonin-treated group, MSC-treated group, and combined treated group (Melatonin-MSCs). We found that COPD was accompanied by deterioration of pulmonary function tests in response to expiratory parameter affection more than inspiratory ones. This was associated with increased Hypoxia inducible factor-1α expression and vascular endothelial growth factor level. Consequently, there was increased CD31 expression indicating increased angiogenesis with massive enlargement of airspaces and thinning of alveolar septa with decreased mean radial alveolar count, in addition to, inflammatory cell infiltration and disruption of the bronchiolar epithelial wall with loss of cilia and blood vessel wall thickening. These findings were improved significantly when Melatonin and bone marrow-derived MSCs were used as a combined treatment proving the hypothesized target that Melatonin might augment MSCs aiming at vascular changes.

Recent advancements in stem cell technology open a new door for patients suffering from diseases and disorders that have yet to be treated. Stem cell-based therapy, including human pluripotent stem cells (hPSCs) and multipotent mesenchymal stem cells (MSCs), has recently emerged as a key player in regenerative medicine. hPSCs are defined as self-renewable cell types conferring the ability to differentiate into various cellular phenotypes of the human body, including three germ layers. MSCs are multipotent progenitor cells possessing self-renewal ability (limited in vitro) and differentiation potential into mesenchymal lineages, according to the International Society for Cell and Gene Therapy (ISCT). This review provides an update on recent clinical applications using either hPSCs or MSCs derived from bone marrow (BM), adipose tissue (AT), or the umbilical cord (UC) for the treatment of human diseases, including neurological disorders, pulmonary dysfunctions, metabolic/endocrine-related diseases, reproductive disorders, skin burns, and cardiovascular conditions. Moreover, we discuss our own clinical trial experiences on targeted therapies using MSCs in a clinical setting, and we propose and discuss the MSC tissue origin concept and how MSC origin may contribute to the role of MSCs in downstream applications, with the ultimate objective of facilitating translational research in regenerative medicine into clinical applications. The mechanisms discussed here support the proposed hypothesis that BM-MSCs are potentially good candidates for brain and spinal cord injury treatment, AT-MSCs are potentially good candidates for reproductive disorder treatment and skin regeneration, and UC-MSCs are potentially good candidates for pulmonary disease and acute respiratory distress syndrome treatment.

COPD is an incurable disorder, characterized by a progressive alveolar tissue destruction and defective mechanisms of repair and defense leading to emphysema. Currently, treatment for COPD is exclusively symptomatic; therefore, stem cell-based therapies represent a promising therapeutic approach to regenerate damaged structures of the respiratory system and restore lung function. The aim of this study was to provide a quantitative synthesis of the efficacy profile of stem cell-based regenerative therapies and derived products in COPD patients. A systematic review and meta-analysis was performed according to PRISMA-P. Data from 371 COPD patients were extracted from 11 studies. Active treatments elicited a strong tendency towards significance in FEV1 improvement (+71 mL 95% CI -2−145; p = 0.056) and significantly increased 6MWT (52 m 95% CI 18−87; p < 0.05) vs. baseline or control. Active treatments did not reduce the risk of hospitalization due to acute exacerbations (RR 0.77 95% CI 0.40−1.49; p > 0.05). This study suggests that stem cell-based regenerative therapies and derived products may be effective to treat COPD patients, but the current evidence comes from small clinical trials. Large and well-designed randomized controlled trials are needed to really quantify the beneficial impact of stem cell-based regenerative therapy and derived products in COPD.