Clinical Study of the Efficacy and Safety of the Application of Allogeneic Mesenchymal (Stromal) Cells of Bone Marrow, Cultured Under the Hypoxia in the Treatment of Patients With Severe Pulmonary Emphysema
Clinical Study of the Efficacy and Safety of the Application of Allogeneic Mesenchymal (Stromal) Cells of Bone Marrow, Cultured Under the Hypoxia in the Treatment of Patients With Severe Pulmonary Emphysema
Actively developing stem cells (SCs) transplantation techniques cause natural interest to the
 problem of regeneration in the lungs. Numerous experimental studies proved the benefits of
 different types of SCs in experimental models of pulmonary emphysema (PE).

 G. Zhen et al. have shown that the transplantation of mesenchymal stem cells (MSCs) to rats
 with papain-induced emphysema leads to their migration into the lungs, differentiation into
 type 2 alveolocytes, and inhibition of apoptosis and prevention PE.

 K. Schweitzer et al. have proved the activity of inflammation in the airways, alveolocytes
 and endothelial cells apoptosis decreased after adipose SCs intravenous administration to
 mice with emphysema caused by chronic exposure to tobacco smoke or VEGF receptors blockade.
 The study of E.P. Ingenito et al. found that endobronchial installed MSCs engraft into the
 alveolar wall and peribronchial interstitium and release integrins, extracellular matrix
 components (collagen IV, laminin and fibrillin), platelet-derived growth factor receptor and
 transforming growth factor β2.

 Our study also found reliable deterrent effect of allogeneic bone marrow MSCs on the
 development of elastase-induced emphysema in rats at different terms of transplantation.

 After the success of pilot studies have started clinical trials. Currently, the website
 http://www. ClinicalTrials.gov reported three studies evaluating the efficacy and safety of
 MSC transplantation in patients with COPD and emphysema. Two of them have already been
 completed and the results of the first pilot project published.

 Authors on the example of 4 patients showed a complete absence of adverse effects, improved
 quality of life and stability of functional parameters at 12 months after starting treatment
 One of the problems of MSC transplantation in patients with respiratory failure is an
 accelerated apoptosis of transplanted cells under the influence of proinflammatory cytokines
 and oxidative stress. Since it is proved that preconditioning MSCs under hypoxia increases
 their survival in hypoxic conditions, increases the expression of growth factors and
 antiinflammatory cytokines, we suppose that MSCs grown in hypoxic medium may have a
 significant positive effect on the disease.
Inclusion Criteria:

 -  HRCT-confirmed diagnosis of lung emphysema by two independent radiologists

 -  post-bronchodilator FEV1/FVC ratio < 0.7

 -  post-bronchodilator FEV1 % predicted value ≥ 20% and < 50%

 -  age 35 and 75 years of, of either sex, and of any race

 -  current or ex-smoker, with a cigarette smoking history ≥ 10 pack-years

 Exclusion Criteria:

 -  • asthma or other clinically relevant lung disease other than COPD (e.g. restrictive
 lung diseases, sarcoidosis, tuberculosis, idiopathic pulmonary fibrosis, or lung
 cancer)

 -  α1-Antitrypsin deficiency

 -  Presence of bullae (more than 10 cm in the diameter)

 -  active infection within 4 weeks of screening

 -  significant exacerbation of COPD or has required mechanical ventilation within 4
 weeks of screening

 -  clinically relevant uncontrolled medical condition not associated with COPD

 -  documented history of uncontrolled heart failure

 -  pulmonary hypertension due to left heart condition

 -  Subject has evidence of active malignancy, or prior history of active malignancy

 -  Subject has a life expectancy of < 6 months