Cell Therapy Decreases Inflammation and Improves the Morphology of the Lung Parenchyma in a Murine Model of Cigarette Smoke-Induced Emphysema

Longhini-dos-Santos, Nathalia; Barbosa-de-Oliveira, Valter Abraao; Stessuk, Talita; Sakalem, Marna Eliana; Ribeiro-Paes, João Tadeu

doi:10.31871/ijntr.4.1.24

Cited by 3 publications

(1 citation statement)

References 29 publications

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“…Adipose tissue is an easily accessible source for obtaining MSC by means of less invasive procedures with lower incidence of morbidity and mortality. Adipose-derived mesenchymal stromal cells (ADSCs) have been extensively utilized in regenerative medicine for various pathological conditions in human patients, including in preclinical studies and clinical trials (from bench to bedside) (2,(5)(6)(7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Genomic instability in long-term culture of human adipose-derived mesenchymal stromal cells

Malagutti-Ferreira

Crispim

Barufatti

et al. 2023

Braz J Med Biol Res

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Mesenchymal stromal/stem cells stem (MSC) have been widely studied due to their great potential for application in tissue engineering and regenerative and translational medicine. In MSC-based therapy for human diseases, cell proliferation is required to obtain a large and adequate number of cells to ensure therapeutic efficacy. During in vitro culture, cells are under an artificial environment and manipulative stress that can affect genetic stability. Several regulatory agencies have established guidelines to ensure greater safety in cell-based regenerative and translational medicine, but there is no specific definition about the maximum number of passages that ensure the lowest possible risk in MSC-based regenerative medicine. In this context, the aim of this study was to analyze DNA damage and chromosome alterations in adipose-derived mesenchymal stromal cells (ADMSC) until the eleventh passage and to provide additional subsidies to regulatory agencies related to number of passages in these cells. Thus, two methods in genetic toxicology were adopted: comet assay and micronucleus test. The comet assay results showed an increase in DNA damage from the fifth passage onwards. The micronucleus test showed a statistically significant increase of micronucleus from the seventh passage onwards, indicating a possible mutagenic effect associated with the increase in the number of passages. Based on these results, it is important to emphasize the need to assess genetic toxicology and inclusion of new guidelines by regulatory agencies to guarantee the safety of MSC-based therapies for human diseases.

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Section: Introductionmentioning

confidence: 99%

Genomic instability in long-term culture of human adipose-derived mesenchymal stromal cells

Malagutti-Ferreira

Crispim

Barufatti

et al. 2023

Braz J Med Biol Res

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Mesenchymal stromal cells-based therapy in a murine model of elastase-induced emphysema: Simvastatin as a potential adjuvant in cellular homing

Faria

Júnior

Coelho

et al. 2021

Pulmonary Pharmacology & Therapeutics

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Autologous Infusion of Bone Marrow and Mesenchymal Stromal Cells in Patients with Chronic Obstructive Pulmonary Disease: Phase I Randomized Clinical Trial

SD¹,

EJ²,

Fiss³

et al. 2021

COPD

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Background and Objectives Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar walls, chronic inflammation and persistent respiratory symptoms. There is no curative clinical treatment for COPD. In this context, cell-based therapy is a promising therapeutic alternative for COPD. Thus, in this open, controlled and randomized Phase I Clinical Trial, we aimed to assess the safety of the infusion of autologous bone marrow mononuclear cells (BMMC), adipose-derived mesenchymal stromal cells (ADSC) and, especially, the safety of concomitant infusion (co-infusion) of BMMC and ADSC as a new therapeutic alternative for COPD. The rationale for co-infusion of BMMC and ADSC is based on the hypothesis of an additive or synergistic therapeutic effect resulting from this association. Methods To achieve the proposed objectives, twenty patients with moderate-to-severe COPD were randomly divided into four groups: control group – patients receiving conventional treatment; BMMC group – patients receiving only BMMC; ADSC group – patients receiving only ADSC, and co-infusion group – patients receiving the concomitant infusion of BMMC and ADSC. Patients were assessed for pulmonary function, biochemical profile, and quality of life over a 12 months follow-up. Results No adverse events were detected immediately after the infusion of BMMC, ADSC or co-infusion. In the 12-month follow-up, no causal relationship was established between adverse events and cell therapy procedures. Regarding the efficacy, the BMMC group showed an increase in forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide (DLCO). Co-infusion group showed a DLCO, and gas exchange improvement and a better quality of life. Conclusion The results obtained allow us to conclude that cell-based therapy with co-infusion of BMMC and ADSC is a safe procedure and a promising therapeutic for COPD. However, additional studies with a greater number of patients are needed before randomized and controlled Phase III clinical trials can be implemented.

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Cell Therapy Decreases Inflammation and Improves the Morphology of the Lung Parenchyma in a Murine Model of Cigarette Smoke-Induced Emphysema

Cited by 3 publications

References 29 publications

Genomic instability in long-term culture of human adipose-derived mesenchymal stromal cells

Genomic instability in long-term culture of human adipose-derived mesenchymal stromal cells

Mesenchymal stromal cells-based therapy in a murine model of elastase-induced emphysema: Simvastatin as a potential adjuvant in cellular homing

Autologous Infusion of Bone Marrow and Mesenchymal Stromal Cells in Patients with Chronic Obstructive Pulmonary Disease: Phase I Randomized Clinical Trial

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