An Exploratory Study on the Treatment of Chronic Obstructive Pulmonary Disease With Autologous Bronchial Basal Cell Transplantation

Study Overview
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Brief Summary
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Chronic obstructive pulmonary disease(COPD)is characterized by recurrent cough, expectoration and asthma, and eventually develop chronic pulmonary heart disease ,chronic respiratory failure and even death. The current clinical treatments for these patients are symptomatic treatment cannot solve the problem of the damaged lung structure fundamentally. Recent studies show that bronchial basement the layer of cells is a kind of cells in the bronchial epithelial basal layer position, the specific expression of Krt5 antigen with the regeneration and repair of lung function , these cells have the activity similar to adult tissue stem cells. Its division and migration are more active and can continue to produce new cells to complement the death of other types of epithelial cells with functional plasticity which can be used to direct repair the bronchial and alveolar structures. It has been proved that bronchial basal cell transplantation can repair the damaged lungs of experimental animals . The bronchial basal cells from autologous tissue, so there is no immune rejection problem. Also because the bronchial basal cells derived from adult tissues which is a part of the body, so there is no risk of a tumor (in animal experiments, In animal experiments, bronchial basal cells transtracheal input 100 times in human dose still no tumor formation). In the early stage, patients with COPD (2 cases), bronchiectasis (2 cases) and interstitial lung disease (1 case) received the treatment, and the overall effect was good. Diseases were alleviated and recovered to some different extend.The study was to brush bronchial basal cells through fiberbronchoscopy in COPD patients and cultured in vitro, and then through the bronchoscope transfusion to the lesion site. To preliminary evaluate the efficacy and safety of autologous bronchial basal cells in the treatment of chronic obstructive pulmonary disease.

Detailed Description
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Between November 2016 and November 2019, the investigators initially recruited 20 with stable COPD patients. Primary evaluations including medical history, physical examination, anthropometric data, blood routine, blood biochemistry, blood coagulation, electrocardiogram,high resolution chest CT, arterial blood gas, pulmonary function test,6-min walking test(6MWT),modified medical research council(MMRC),St George's respiratory questionnaire(SGRQ). After initial evaluation, the investigators obtained extraction bronchial basal cells micro tissue from 3 4 grade bronchus to by mean of fiberbronchoscopy, then purified and selectively amplified bronchial basal cells to reserve .The basal layer cell culture system for our partners (Regend Therapeutics) patented technology using culture medium containing special combination of growth factors and composite materials to simulated composite basal layer environment and can selectively amplified bronchial basal cells, while other types of mature epithelial cells and fibroblasts could not grow naturally. After a period of time, the basal lamina of the bronchial epithelial cells can be stored in the liquid nitrogen cell bank for a long time. Before applied to the patient, bronchial basal cells need to go through a series of strict examination. Then, bronchoscopy was performed again and the bronchial basal lamina suspension was injected directly into the lesion site . Estimate the change of respiratory function(symptoms, signs, chest CT, pulmonary function, the 6 minute walk test, MMRC, SGRQ etc) and serum index in third days , first months, third months, sixth months and first years of the follow-up after treatment respectively, to evaluate the safety and efficiency of autologous bronchial basal cells for treatment of COPD .

Official Title
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Huai'an First People 's Hospital,Nanjing Medical University

Conditions
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Cell Transplantation

Intervention / Treatment
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* Other: autologous bronchial basal cell transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged between 18 to 70 years according to the guideline criteria, the diagnosis of COPD: ①There is a chronic cough, sputum or gas breathing symptoms such as promoting ②Pulmonary function tests showed airflow limitation(FEV1<80% predicted value，FEV1/FVC<0.7) CT imaging and hematological examination excluded other lung diseases. stable disease for more than 2 weeks patients who were able to tolerate fiberoptic bronchoscopy to sign the informed consent form Exclusion Criteria: women who are pregnant, nursing or not taking effective contraception syphilis, HIV antibody positive person there is a history of alcohol or illicit drug abuse patients who had received any other clinical trial within the first 3 months poor compliance, it is difficult to complete the study researchers believe there may be any increase in the risk of the subject or any interference with the clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: COPD group(self control)<br>Prior treatment:20 stable COPD patients were enrolled,estimated the respiratory function and serum index Intervention:autologous bronchial basal cell transplantation After treatment:Estimate the change of respiratory function and serum index in third days , first months, third months, sixth months and first years of the follow-up after treatment respectively | Other: autologous bronchial basal cell transplantation<br>* the investigators obtained extraction bronchial basal cells micro tissue from 3 4 grade bronchus, then purified and selectively amplified bronchial basal cells to reserve . After a period of time, the basal lamina of the bronchial epithelial cells can be stored in the liquid nitrogen cell bank for a long time. Before applied to the patient, bronchial basal cells need to go through a series of strict examination. Then, bronchoscopy was performed again and the bronchial basal lamina suspension was injected directly into the lesion site .<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| forced expiratory volume in one second(FEV1) | as the severity of chronic obstructive pulmonary disease(COPD)estimated by pulmonary function | 24 months | 
| chest high-resolution computed tomography | as the severity of lung hyperinflation estimated by radiological | 24 months | 
| arterial blood gas | to assess the level of hypoxemia and hypercapnia in chronic obstructive pulmonary disease(COPD) patients | 24 months | 
| 6MWT | 6 min walking test, to evaluate the exercise function in patients with moderate and severe pulmonary heart diseases | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| forced vital capacity(FVC) | an index of pulmonary function in chronic obstructive pulmonary disease(COPD) patients | 24 months | 
| MMRC | an index to evaluate the lever of dyspnea | 24 months | 
| SGRQ | a questionnaire to assess the influence of chronic airflow restriction on the quality of life, including symptoms, activities and daily life affected by diseases | 24 months |