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Autologous transplantation of P63+ lung progenitor cells for chronic obstructive pulmonary disease therapy

ABSTRACT: Autologous transplantation of P63+ lung progenitor cells for chronic obstructive pulmonary disease therapy

PROVIDER: PRJNA990808 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25118589.fastq.gz	Fastqsanger.gz
	SRR25118590.fastq.gz	Fastqsanger.gz
	SRR25118591.fastq.gz	Fastqsanger.gz
	SRR25118592.fastq.gz	Fastqsanger.gz
	SRR25118593.fastq.gz	Fastqsanger.gz

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Autologous transplantation of P63+ lung progenitor cells for chronic obstructive pulmonary disease therapy

Project description:Adult lung resident stem/progenitor cells, including P63+ progenitor cells, have demonstrated the capacity for regeneration of lung epithelium in precinical models. Here we report a clinical trial of intra-pulmonary P63+ progenitor cell transplantation which included 28 participants with chronic obstructive pulmonary disease (COPD) (stage II~IV). For control group, standard of care (SOC) for COPD treatment was given. For intervention group, in addition to SOC, autologous P63+ progenitor cells were isolated from the airway basal layer via bronchoscopic brushing, cultured for 3~5 weeks, and then transplanted into the lungs via bronchoscopy with 0.7-5.2x10^6 cells per kilogram bodyweight. Eventually 20 patients were evaluated (intervention group n=17; control group n=3). No grade 3~5 adverse events (AE) or serious adverse events occurred in any group. Bronchoscopy-associated AEs were recorded only in intervention groups, while the other AEs were recorded in both groups without showing significant difference. Participants in intervention group displayed significant improvement in diffusing capacity of the lung for carbon monoxide (DLCO) (change from baseline, 24 weeks: +18.2%), showing significant difference comparing to control group (change from baseline, 24 weeks: -17.4%)(p-value=0.008). Furthermore, more participants in intervention group showed > 30 m increase in walking distance within 6 minutes, demonstrating significant difference comparing to control group (p-value=0.036). Transcriptomic analysis of cells isolated from responding and non-responding individuals in the intervention group showed that higher expression of P63 and Nkx homeobox-1 was associated with better efficacy. In conclusion, transplantation of cultured P63+ lung progenitor cells was safe and represented a potential treatment strategy for COPD.

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Autologous transplantation of P63+ lung progenitor cells in patients with bronchiectasis: a randomized, single-blind, controlled trial

Project description:Non-cystic fibrosis bronchiectasis is a severe respiratory disease characterized by progressive loss of lung function, resulting in high morbidity and even early mortality. Current treatments cannot repair progressive lung damage, which encouraged the exploration of stem and progenitor cell-based regenerative therapies. In current study, we found that the P63+ progenitor cells normally located in airway basal layer could appear in the alveolar spaces of bronchiectasis patients. We successfully cloned and expanded the progenitor cells from the airway brushing tissues of patients. Then we conducted a randomized, single-blind, controlled, phase 1/2 trial to evaluate the safety and efficacy of autologous P63+ progenitor cells transplantation in bronchiectasis patients.

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Project description:Diaphragm muscles in Chronic Obstructive Pulmonary Disease (COPD) patients undergo an adaptive fast to slow transformation that includes cellular adaptations. This project studies the signaling mechanisms responsible for this transformation. Keywords: other

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Autologous transplantation of P63+ lung progenitor cells in patients with bronchiectasis: a randomized, single-blind, controlled trial

Project description:Autologous transplantation of P63+ lung progenitor cells in patients with bronchiectasis: a randomized, single-blind, controlled trial

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