What is Lung : -

The Lungs are the essential respiratory organ in air breathing living beings and lungs are a pair of spongy, air-filled organs, located near the backbone on either side of the heart. Trachea (windpipe) conducts inhaled air into the lungs through its tubular branches called bronchi. The bronchi then divide into smaller and smaller (bronchioles), finally becoming microscope. The principal function is to transport oxygen from the atmosphere into the bloodstream , and to release CO2 from the bloodstream into the atmosphere.

There is one another type of cells alveoli in lungs where all bronchioles end in cluster. In alveoli, oxygen from air is absorbed into the blood and CO2 which is waste product of metabolism, travels from the blood to the alveoli, where it can be exhaled. Between the alveoli is a thin layer of cells called interstitium, which contains blood vessels and cells that help support the alveoli.

The lungs are covered by a thin tissue layer called pleura, a thin layer of fluid acts as a lubricant allowing the lungs to slip smoothly as they expand and contract with each breath.

Stem Cell therapy For Lung or Pulmonary disease:-

Lung disease is leading causes of morbidity and mortality worldwide. Pulmonary diseases characterized by loss of lung elasticity, small airway tethers, and luminal obstruction with inflammatory mucoid secretions and excessive matrix deposition and destruction of the normal lung architecture.

Regeneration of pulmonary tissue by stem cells transplantation from endogenous, exogenous, is a promising novel therapy. The use of adult stem cells to help with lung regeneration and repair could be a newer technology in clinical and regenerative medicine. In fact, different studies have shown that stem cells contribute to repair and remodeling of lung in animal and human models of progressive pulmonary diseases.

Types of Lung Disease Treated by Stem Cell Therapy:-

1. Idiopathic Pulmonary Fibrosis (IPF):- IPF is an interstitial inflammatory disease with unknown etiology characterized by scarring and fibrosis of the lungs that ultimately result in terminal pulmonary insufficiency. Mesenchymal stem cell transplantation in IPF disease provides

1. Secrete anti-inflammatory cytokines so stop or reduce further inflammation and collagen deposition (Neuringer et al.; 2006, Ortiz et al., 2003) on lung cells
2. Regenerate the lung injured/damaged cells via differentiating into lung progenitor cells
3. Induce/activate resident stem cells in the lung via para/auto-crine signaling.
4. Mesenchymal Stem Cells transplantation provides anti-apoptic, immune modulation, anti-inflammatory and anti- fibrosis properties so this environment may accommodate the cells indefinitely and control their self-renewal and progeny production in vivo or refine their ability to induce host reparative processes.

2. Chronic obstructive pulmonary disease (COPD):- COPD is a lung disease which includes both chronic bronchitis and emphysema. COPD is one of the leading causes of death and disability in all over the world and which results predominantly from cigarette smoking.
There are two main forms of COPD:-

• “Chronic bronchitis” is a chronic inflammation of the bronchi (medium-size airways) in the lungs which involves a long-term cough with mucus
• “Emphysema” which is called an obstructive lung disease because the destruction of lung tissue around smaller sacs, called alveoli, makes these air sacs unable to hold their functional shape upon exhalation. Emphysema is most often caused by tobacco smoking and long-term exposure to air pollution involves destruction of the lungs over time

Mesenchymal stem cell transplantation has many advantages in COPD patient follow as:-

1. Secrete anti-inflammatory cytokines so stop or reduce further inflammation and collagen deposition (Neuringer et al.; 2006, Ortiz et al., 2003) on lung bronchi cell
2. Regenerate the bronchi and alveoli injured/damaged cells via differentiating into lung progenitor cells
3. Induce/activate resident stem cells in the lung via para/auto-crine signaling.
4. Mesenchymal Stem Cells transplantation provides anti-apoptic, immune modulation, anti-inflammatory and anti- fibrosis properties so this environment may accommodate the cells indefinitely and control their self-renewal and progeny production in vivo or refine their ability to induce host reparative processes

Protocol Outline for Chronic Kidney Disease (CKD): -

1. We transplant “Bone marrow-derived stem cells concentrate (BMSCs)” via intrathecally/intravenously because it provides a rich growth factor (VEGF, TGF-ß, FGF) environment that may enhance the neuron formation. The iliac crest contains bone marrow which is a rich source of the regenerative cells including:-
   • Mesenchymal Stem Cells (MSCs, CD44+)):- MSCs which differentiate into many types of cells such as bone, cartilage, neuron and so more.
   • Hematopoietic Stem Cells (HSCs, CD34+)):- HSCs which differentiate into all types of blood cells and also provide enhance environment for MSCs activation.
   • Endothelial Stem Cells (ESCs, CD31+)):- ESCs which differentiate into all types of blood vessels.
   • Platelets: -
     1. To modulate the regeneration process
     2. Recruit bone marrow progenitor cells to loci of injury
     3. Provides adhesion site for stem cells
     4. Platelets fibrin provides migration highway at the site of injury
2. We infuse cultured mesenchymal stem cells isolated from bone marrow/cord tissue via intravenously and bronchoscope guided injection into the lobes of lung directly because MSCs is the multipotent cell which is able to differentiate into damaged lung cells and also provide new cells for the repair and remodeling of damaged tissues in the lung.

Follow-up with patients:-

Our medical staff members will be in contact with patients to get complete follow-up at 1, 3, 6 months and I year interval.

Scientific Articles:-
1. Tzouvelekis et al. 2011 (Journal of Translational Medicine). Stem cell therapy for idiopathic pulmonary fibrosis: a protocol proposal.

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