Adipose-Derived Mesenchymal Stem Cells (ADSCs) Have Anti-Fibrotic Effects on Lung Fibroblasts from Idiopathic Pulmonary Fibrosis (IPF) Patients DOI Creative Commons

Noriko Ouji-Sageshima,

Akihiko Hiyama,

Makiko Kumamoto

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(24), P. 2050 - 2050

Published: Dec. 12, 2024

Idiopathic pulmonary fibrosis (IPF) is the most common type of in lungs, characterized as a chronic and progressive interstitial lung disease involving pathological findings with median survival 3 years. Despite knowledge accumulated regarding IPF from basic clinical research, an effective medical therapy for condition remains to be established. Thus, it necessary further including stem cell therapy, which will provide new insights into expectations treatment. Recently, has been reported that one therapeutic candidates adipose-derived mesenchymal cells (ADSCs), have several benefits, such easy accessibility minimal morbidity compared bone marrow-derived cells. Therefore, we investigated possibility ADSCs candidate IPF. Using human fibroblasts (LFs) patients, demonstrated LFs cocultured led reduced fibrosis-related genes. Further analysis revealed prevented activation ERK signaling pathway via upregulation protein tyrosine phosphatase receptor-type R (PTPRR), negatively regulates pathway. Moreover, intravascular administration improved pathogenesis bleomycin-induced collagen deposition histology hydroxyproline quantification markers gene expression types I III α-smooth muscle actin (α-SMA) murine model. ADSC transfer was also humanized mouse model induced infusion LFs, because bleomycin installation does not fully recapitulate model, found fibrotic changes lungs. These suggest are promising

Language: Английский

Highlights on Future Treatments of IPF: Clues and Pitfalls DOI Open Access

Alessandro Libra,

Enrico Sciacca,

Giuseppe Muscato

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8392 - 8392

Published: Aug. 1, 2024

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by irreversible scarring of tissue, leading to death. Despite recent advancements in understanding its pathophysiology, IPF remains elusive, and therapeutic options are limited non-curative. This review aims synthesize the latest research developments, focusing on molecular mechanisms driving related emerging treatments. Unfortunately, several phase 2 studies showing promising preliminary results did not meet primary endpoints subsequent 3, underlying complexity need for new integrated endpoints. a challenging condition with complex interplay genetic, epigenetic, pathophysiological factors. Ongoing into keystones critical development targeted therapies that could potentially stop progression disease. Future directions include personalized medicine approaches, artificial intelligence integration, growth genetic insights, novel drug targets.

Language: Английский

Citations

9
Preclinical Evaluation of the Safety, Toxicity and Efficacy of Genetically Modified Wharton’s Jelly Mesenchymal Stem/Stromal Cells Expressing the Antimicrobial Peptide SE-33 DOI Creative Commons

Vagif Ali oglu Gasanov,

Dmitry Kashirskikh, Victoria A. Khotina

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 341 - 341

Published: Feb. 26, 2025

Mesenchymal stem/stromal cells (MSCs) offer promising therapeutic potential in cell-based therapies for various diseases. However, the safety of genetically modified MSCs remains poorly understood. This study aimed to evaluate general toxicity and Wharton's Jelly-Derived (WJ-MSCs) engineered express antimicrobial peptide SE-33 an animal model. Genetically WJ-MSCs expressing were administered C57BL/6 mice at both excessive doses, either once or repeatedly. Animal monitoring included mortality, clinical signs, behavioral observations. The assessment involved histopathological, hematological, biochemical analyses major organs tissues, while immunotoxicity immunogenicity examined through humoral cellular immune responses, macrophage phagocytic activity, lymphocyte blast transformation. Antimicrobial efficacy was evaluated a Staphylococcus aureus-induced pneumonia model by mortality assessing bacterial load inflammatory processes lungs. Mice receiving exhibited no acute chronic toxicity, abnormalities, pathological changes, regardless dose administration frequency. No significant alterations responses observed, there notable changes hematological serum parameters. Infected animals treated with WJ-MSC-SE33 showed reduction lung inflammation improved survival compared control groups, demonstrating over native WJ-MSCs. Our findings suggest that are well tolerated, displaying favorable profile comparable potent significantly reducing load, inflammation, S. aureus These data support as candidate infections, particularly those complicated antibiotic resistance.

Language: Английский

Citations

1
Novel drug discovery strategies for chronic obstructive pulmonary disease: the latest developments DOI
Luigino Calzetta,

Elena Pistocchini,

Shima Gholamalishahi

et al.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: April 14, 2025

The journey from initial drug discovery to approval for respiratory diseases typically spans approximately 10.4 years and cost over $2.8 billion. This intricate process involves five stages: target identification, therapeutic molecule discovery, preclinical testing, clinical trials, regulatory approval. review examines novel strategies chronic obstructive pulmonary disease (COPD), focusing on advanced in vitro models that replicate human lung conditions accurate testing according the following search string: AND strategy COPD. It explores targeted molecular therapies, structure-based design, repurposing approaches facilitated by computational analysis. significance of personalized medicine tailoring treatments diverse COPDs is emphasized, highlighting complexity necessity these innovative methodologies improve outcomes. COPD remains a challenging area, with significant unmet medical need. Despite previous efforts, few effective therapies exist. Innovative models, are showing promise. Emphasizing existing drugs could transform treatment paradigms, promoting more complex like These innovations hold potential enhancing efficiency, leading precision approaches.

Language: Английский

Citations

1
Human Mesenchymal Stem Cell Therapy: Potential Advances for Reducing Cystic Fibrosis Infection and Organ Inflammation DOI Creative Commons
Tracey L. Bonfield, Hillard M. Lazarus

Best Practice & Research Clinical Haematology, Journal Year: 2025, Volume and Issue: 38(1), P. 101602 - 101602

Published: March 1, 2025

Language: Английский

Citations

0
A review of the immunomodulatory properties of mesenchymal stem cells and their derived extracellular vesicles in small-cell and non-small-cell lung cancer cells DOI

Radhwan Abdul Kareem,

Hayder Naji Sameer,

Ahmed Yaseen

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 146, P. 113848 - 113848

Published: Dec. 17, 2024

Language: Английский

Citations

0
Adipose-Derived Mesenchymal Stem Cells (ADSCs) Have Anti-Fibrotic Effects on Lung Fibroblasts from Idiopathic Pulmonary Fibrosis (IPF) Patients DOI Creative Commons

Noriko Ouji-Sageshima,

Akihiko Hiyama,

Makiko Kumamoto

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(24), P. 2050 - 2050

Published: Dec. 12, 2024

Idiopathic pulmonary fibrosis (IPF) is the most common type of in lungs, characterized as a chronic and progressive interstitial lung disease involving pathological findings with median survival 3 years. Despite knowledge accumulated regarding IPF from basic clinical research, an effective medical therapy for condition remains to be established. Thus, it necessary further including stem cell therapy, which will provide new insights into expectations treatment. Recently, has been reported that one therapeutic candidates adipose-derived mesenchymal cells (ADSCs), have several benefits, such easy accessibility minimal morbidity compared bone marrow-derived cells. Therefore, we investigated possibility ADSCs candidate IPF. Using human fibroblasts (LFs) patients, demonstrated LFs cocultured led reduced fibrosis-related genes. Further analysis revealed prevented activation ERK signaling pathway via upregulation protein tyrosine phosphatase receptor-type R (PTPRR), negatively regulates pathway. Moreover, intravascular administration improved pathogenesis bleomycin-induced collagen deposition histology hydroxyproline quantification markers gene expression types I III α-smooth muscle actin (α-SMA) murine model. ADSC transfer was also humanized mouse model induced infusion LFs, because bleomycin installation does not fully recapitulate model, found fibrotic changes lungs. These suggest are promising

Language: Английский

Citations

0