Clinical indications: (IPF) of Idiopathic Pulmonary Fibrosis, (COPD) of chronic obstructive Pulmonary Disease, (BE) of bronchiectasis.

At this stage, the main indications of the company's clinical research are major lung injury diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and bronchiectasis.

The main characteristics of respiratory diseases such as bronchiectasis (BE), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary disease (ILD) are that the disease progresses and aggravates year by year, which often lasts for several years, which is difficult to cure and eventually leads to death.

Among them, Idiopathic Pulmonary Fibrosis (IPF), also known as Idiopathic Pulmonary Interstitial Fibrosis, is a special serious type of interstitial lung disease. It has been included in the list of the first batch of rare diseases jointly formulated by the National Health and Health Council and other five departments in 2018.

IPF lesions are limited to the lungs, mostly in people over 50 years old, and the clinical manifestations are progressive dyspnea.

The characteristic histopathological change of IPF is common interstitial pneumonia.

The pathological changes of common interstitial pneumonia have two typical characteristics: 1) heterogeneous pathological changes, inflammation, fibrosis and honeycomb changes in the stroma, and 2) different severity of pathological changes. The coexistence of new and old is an important basis for the diagnosis of common interstitial pneumonia.

The main lesions of IPF were fibrosis, the degree and distribution of lesions were not consistent, observed under low power microscope, at the same time, scar fibrosis area was accompanied by honeycomb lung changes, and the lesion was mild or even normal lung tissue area.

These pathological changes are usually characterized by subpleural and para-septum pulmonary parenchyma.

Inflammation is usually mild, with a small number of lymphocytes and plasma cell stroma infiltration, with proliferation of type 2 alveolar epithelial cells and bronchiole epithelial cells.

The fibrosis area is mainly composed of dense collagen fibers, and scattered fibroblasts can be seen.

The honeycomb lung area consists of a cystic fibrotic air cavity, usually lined with bronchiole epithelial cells, filled with mucus and inflammatory cells.

Smooth muscle hyperplasia can be seen in the lung stroma in the area of pulmonary fibrosis and honeycomb lung disease.

The lung injury continues to progress and is irreversible.

The lack of the number of alveoli leads to the low or even loss of pulmonary ventilation function, which leads to hypoxia, decreased activity and even death.

Therefore, the average survival time after IPF diagnosis was only 2.8 years, and the mortality rate was higher than that of most tumors.

At present, the traditional treatment of IPF is mainly to take anti-inflammatory drugs and anti-fibrosis drugs.

At present, the IPF drugs approved for sale in China are pyrifenidone, (Pirfenidone), nitannib (Nintedanib) and acetylcysteine.

They can delay the decline of pulmonary function, but it is difficult to improve pulmonary

function or reverse the course of disease.

At present, in addition to whole lung transplantation for IPF, there is a lack of effective conventional treatment all over the world. The fundamental reason lies in the lack of effective methods to regenerate and repair the injured alveolar structure.

The regeneration and repair technology based on stem cell transplantation is the most promising scheme for the treatment of IPF.

Principle of transplantation of pulmonary stem cells (bronchial basal cells) in the treatment of pulmonary injury.

The pathogenesis of IPF in idiopathic pulmonary fibrosis is mainly related to the imbalance of alveolar injury and repair.

Most of the pathological changes of IPF are due to the damage and abnormal repair of alveolar epithelial cells. Once the regeneration of damaged alveolar epithelial cells is blocked, a large number of fibroblasts in the stroma will proliferate instead, which is why a large number of fibroblasts can be seen in the injured site.

Fibroblasts secrete collagen and other fibrous factors deposited in the lung, which further aggravate the injury of alveoli, interfere with normal respiratory function, and eventually lead to the death of patients due to respiratory failure.

Conventional drugs have little effect on alveolar repair and regeneration, and bronchial basal cell transplantation is the most effective way to regenerate alveoli.

Autologous cell transplantation can solve the problem of immune rejection naturally.

The cells transplanted through tracheoscopy will enter the alveolar area through the bronchi. If the cells enter the alveolar area are healthy and intact, the transplanted cells will not regenerate and will be metabolized rapidly within a week. If the alveolar area is damaged, then the cytokine inflammatory microenvironment in the damaged area will create favorable space and conditions for the proliferation, migration and differentiation of the transplanted cells.

After transplantation, it takes about 1 month for the bronchial basal layer cells to gradually differentiate into new alveolar epithelial cells, which are naturally anastomosed with the bronchial structure at the entrance.

At the same time, the transplanted cells secrete angiogenic factors, recruit capillaries in the lung and migrate to the newborn alveoli to reconstruct the blood-gas exchange unit.

According to rough estimates, IPF patients receive every 50 million bronchial basal layer cell transplantation, can regenerate about 20 million functional alveoli.

Considering that there are only 100 to 200 million residual functional alveoli in IPF patients, bronchial basal cell transplantation can improve the pulmonary blood-gas exchange function in IPF patients by 10% to 20%.

From the clinical point of view, it can be shown that the pulmonary carbon monoxide diffusion volume (DLCO) increased gradually one month after cell transplantation.

In addition to regenerating a type of alveolar epithelial cells to directly enhance ventilation function, bronchial basal layer cells also have a barrier function of (barrier) in the lung.

After the injury of the lung parenchyma, it often leads to the imbalance of the formation and reflux balance of the tissue fluid in the lung, so that a large amount of tissue fluid can not be absorbed by the pulmonary lymph and pulmonary vein system in a very short period of time. It accumulates in the alveoli, pulmonary stroma and bronchioles, resulting in serious disturbance of pulmonary ventilation and ventilation function.

Both endogenous and transplanted bronchial basal layer cells can form a tight epithelial barrier at the site of lung injury, prevent vascular leakage, inhibit the occurrence of pulmonary edema and inhibit the proliferation of fibroblasts.

In addition, this barrier can also protect against the invasion of foreign microorganisms, physical and chemical factors and allergens.

Progress of clinical projects.

Regend specializes in human organ regeneration medicine and is a global leader in this field.

Its core product, REGEND001 cell preparation, has been accepted by the State Drug Administration and is the first autologous stem cell product for respiratory diseases in the world.

The company is also the first enterprise in China to be registered by the State Health Commission and the Food and Drug Administration to carry out stem cell clinical research (registration number: CMR-20161214-1002). At the same time, it is also the first batch of enterprises to undertake the key research and development program of the Ministry of Science and Technology of China, "Stem Cell and Transformation Research".

At present, the company has passed ISO9001:2008 quality management system certification, stem cell preparations through China Metrology Certification (CMA), China conformity Assessment Committee (CNAS) and IAF international mutual recognition.

All clinical projects are carried out in strict accordance with the regulations of the National Health Commission and the Drug Administration, and are registered in the ClinicalTrial Global Database of the National Institutes of Health of the United States.

Jimrisheng respiratory stem cell products are exclusive around the world and have completely independent intellectual property rights.

In the past three years, Regend has worked with a number of tertiary hospitals with stem cell clinical research qualifications to carry out a series of clinical studies in the field of pulmonary stem cells and regenerative medicine, involving bronchiectasis (BE), chronic obstructive pulmonary disease (COPD), ILD including IPF and other diseases, and achieved good results.

After treatment, the pulmonary diffusion function of most subjects was significantly improved, and the lung CT images of some severe patients were improved.

Clinical research results have been published in a number of SCI international academic journals and selected as one of the top ten advances in medical biotechnology in China in 2018.

Bronchial basal layer cells can be obtained only by fiberoptic bronchoscopy brushing, and through appropriate methods of isolation and purification and a large number of expansion.

Therefore, the bronchial basal layer cells can come from autologous tissue, solve the problem of immune rejection, and there is no risk of tumor, so it is very safe.

These characteristics make bronchial basal layer cells as a new generation of "seed" cells have unique advantages and good clinical application prospects in the treatment of lung tissue cell injury which can not be repaired naturally.

At present, the main cooperative clinical research hospitals to be launched or under way are Shanghai Oriental Hospital, the first affiliated Hospital of Guangzhou Medical University, Ruijin Hospital affiliated to Medical College of Shanghai Jiaotong University, Zhongshan Hospital affiliated to Fudan University in Shanghai, Peking Union Medical College Hospital and so on.

Domestic and foreign subjects who intend to join can pay attention to the trends of clinical trials in these hospitals in time, register in advance, and prepare for screening and treatment in clinical trials.

You can also keep an eye on the Regend website and the subject recruitment announcements on the official account.

The treatment flow chart of autologous cell transplantation is as follows: