Stem Cell Therapy for Damaged Lungs



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All you need to know before your stem cell therapy for damaged lungs

There is growing evidence that stem cell therapy for damaged lungs is an extremely effective form of treatment. The basis of this evidence lies in recent empirical research that has been conducted relating to pulmonary fibrosis, and the effects that stem cell therapy can have on this debilitating illness.  

Overview of Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is defined as a unique type of chronic, progressive fibrosing (scarring) pneumonia of unknown cause that primarily occurs in older adults and is limited to the lungs [1].  It causes lung scarring that results in reduced oxygen intake over time. It is not presently curable. 

There are seven listed idiopathic interstitial pneumonias in the American Thoracic Society/European Respiratory Society consensus statement: 

  1. Idiopathic pulmonary fibrosis
  2. Nonspecific interstitial pneumonia
  3.   Cryptogenic organizing pneumonia
  4.   Acute interstitial pneumonia
  5.   Desquamative interstitial pneumonia
  6.   Respiratory bronchiolitis-associated interstitial pneumonia
  7.   Lymphoid interstitial pneumonia

Idiopathic pulmonary fibrosis is the most common [10] and has a poor prognosis, and no proven effective therapies beyond lung transplantation [2]

Causes

The current hypothesis regarding the cause of idiopathic pulmonary fibrosis is exposure to an environmental trigger such as smoke, environmental pollutants, dust, viral infections, gastroesophageal reflux disease, chronic aspiration in a susceptible person that leads to alveolar (air sacs in the lungs) surface damage [11]. Reestablishing an intact lining or surface following injury is a key component of normal wound healing. In idiopathic pulmonary fibrosis, after the injury, the immune response results in the migration of repairing proteins. However, these cells do not die off after initially fighting the inflammation to allow the wound to heal and continue to secrete proteins and chemicals that damage and scar the lung, irreversibly [11].

Signs and symptoms

The clinical symptoms of idiopathic pulmonary fibrosis are nonspecific and can be present in other pulmonary and cardiac diseases. Most patients present with a gradual onset (usually more than 6 months) of shortness of breath with exertion and/or a nonproductive cough. In approximately 5% of patients, there are no presenting symptoms when idiopathic pulmonary fibrosis is inadvertently diagnosed.

Systemic symptoms that can occur but are less common are the following:

  • Weight loss
  • Low-grade fevers
  • Fatigue
  • Joint aches
  • Muscle aches

Diagnosis

It is necessary to ask a wide range of questions regarding their past medical history, including medications (current and past), drug use, social history, occupational, recreational, and environmental exposures, and risks for the human immunodeficiency virus to exclude other causes of interstitial lung disease [2]

The diagnosis of IPF requires the following [3]  :

  • Exclusion of known causes of interstitial lung disease
  • Presence of the high-resolution computed tomography (HRCT) pattern of UIP
  • Specific combinations of HRCT patterns and tissue patterns in the lung biopsy

Physical examination in patients with idiopathic pulmonary fibrosis may be:

  • ‘Velcro’ sounding crackles
  • Fingertips that are abnormal called digital clubbing (25-50%)
  • Pulmonary hypertension at rest (20-40%) [4]
  • Loud second heart sound or a tricuspid regurgitation murmur, edema in the feet and ankles

Laboratory testing

 Some tests may help exclude other causes of interstitial lung disease such as following:

  • Antinuclear antibodies or rheumatoid factor titers (levels). Some people with IPF have then but the levels are generally not high[5]. The presence of high titers may suggest a connective tissue disease (autoimmune disease)
  • C-reactive protein level and erythrocyte sedimentation rate may be elevated but nondiagnostic.
  • Complete blood cell count
  • Arterial blood gas analysis to detect chronic hypoxemia (low oxygen) which is common
  • Pulmonary function studies[6]
  • 6-minute walk test (6MWT) is often used in the initial and ongoing clinical assessment of patients with idiopathic pulmonary fibrosis. If oxygen levels go below 88% during a 6MWT, there is a higher chance of mortaility[7]

Imaging studies

  • High-resolution computed tomography (HRCT) scanning is both sensitive and specific for the diagnosis of idiopathic pulmonary fibrosis.
  • Chest radiography: Abnormal findings but not diagnostic. It may demonstrate netlike linear and curving white areas predominantly at the lung bases, honeycomb appearance, and lower lung lobe volume loss [8]
  • Transthoracic echocardiography (ultrasound) can detect pulmonary hypertension [4]

Procedures

  • Bronchoscopy is done by inserting a tube attached to a camera to obtain washings for analysis
  • Surgical lung biopsy can be done via open lung biopsy or video-assisted thoracoscopic surgery (VATS)

Management

The optimal medical therapy for IPF is not clearly defined. Treatment strategies include the management of comorbid conditions such as chronic obstructive pulmonary disease, obstructive sleep apnea, gastroesophageal reflux disease, and coronary artery disease.

  • Encourage tobacco users to quit and offer medication to help.
  • Prescribe oxygen therapy in patients with low blood oxygen at rest or with exercise. The goal is to maintain an oxygen level of at least 90% at rest, while sleeping, and with activity
  • Vaccinations for influenza and pneumococcal infection.

Surgery

  • Lung transplantation: All patients with diagnosed IPF or probable idiopathic pulmonary fibrosis should be referred for lung transplantation evaluation regardless of their medical condition [9]

Pharmacotherapy

  •         Systemic corticosteroids like prednisone
  •         Immunosuppressant agents such as azathioprine and cyclophosphamide
  •         Tyrosine kinase inhibitors like nintedanib
  •         Antifibrotic agents such as pirfenidone

Mesenchymal Stem Cells (MSCs) 

Research into the mobilization of endogenous (from self) stem cells from bone marrow (BM) for tissue repair has attracted researchers’ attention [12, 13]. The BM acts as a storage center for a variety of stem cell populations, which are mobilized to varying degrees into the blood circulation after tissue damage [14]. Endogenous MSCs from BM can travel to damaged tissue where they can help repair and regenerate the tissue with various proteins and directly changing into the cells specific to that tissue. [14-16]

MSCs can be used as an alternative treatment for pulmonary fibrosis (PF) [17]. BM-MSC transplanted into mice significantly reduced lung injury and fibrosis in the animal model of bleomycin (BLM)-induced PF models [18]. In a study conducted by Ortiz in 2003, BM-MSC injection through the jugular vein immediately after being exposed to BLM can significantly reduce PF [19]. In another model of lung damage (SiO2-induced IPF) mice model, human mesenchymal stem cell (hMSC) transplantation directly replaced fibrosis with normal lung cells, reducing IPF symptoms caused by collagen deposition and inflammation [20].

Zhao et al. also proved the therapeutic effects of BM-MSC treatment in BLM-induced lung damage in rats [21].  Furthermore, the data from MSC-based clinical trials support the safety of a single infusion of hMSC in patients with IPF [22]. This is tremendously supportive of the effectiveness of stem cell therapy for lungs that are suffering the negative effects of pulmonary fibrosis. 

Potential of Stem Cell Therapy to Repair Lung Damage

This is just the tip of the iceberg for those looking into stem cell therapy for damaged lungs as a result of pulmonary fibrosis. As more lung stem cell clinical trials are conducted we anticipate growing support from the conservative medical industry in relation to this form of treatment. With growing support, the future will continue to look brighter for many pulmonary fibrosis sufferers needing to travel far and wide in search of effective stem cell treatment. 

How long does it take for Stem Cell therapy to work? 

The effects of Stem Cell Therapy on those with Pulmonary Fibrosis varies, but the majority of sufferers experience immediate improvements to their overall health and well being. 

This is clearly demonstrated through the testimonials of patients who have attended our clinic in Nicosia. 

Can lung tissue regenerate? 

Multiple clinical research trials have shown that Stem Cells can assist in the repair and regeneration of lung tissue by directly transforming into the specific cells that are related to the damaged tissue. [14-16]

References

  1. Raghu G, Collard HR, Egan JJ, Martinez FJ, Behr J, Brown KK. An Official ATS/ERS/JRS/ALAT Statement: Idiopathic Pulmonary Fibrosis: Evidence-based Guidelines for Diagnosis and Management. Am J Respir Crit Care Med. 2011 Mar 15. 183(6):788-824. [Medline].

  2. Frankel SK, Schwarz MI. Update in idiopathic pulmonary fibrosis. Curr Opin Pulm Med. 2009 Sep. 15(5):463-9. [Medline].

  3. [Guideline] Raghu G, Remy-Jardin M, Myers JL, et al. Diagnosis of Idiopathic Pulmonary Fibrosis. An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. Am J Respir Crit Care Med. 2018 Sep 1. 198 (5):e44-e68. [Medline].

  4. Patel NM, Lederer DJ, Borczuk AC, Kawut SM. Pulmonary hypertension in idiopathic pulmonary fibrosis. Chest. 2007 Sep. 132(3):998-1006. [Medline].

  5. Fishman A, Elias J, Fishman J, Grippi M, Senior R, Pack A. Idiopathic Pulmonary Fibrosis. Fishman AP. Fishman's Pulmonary Diseases and Disorders. 4th ed. The McGraw-Hill Companies, Inc.; 2008. Vol 1: 1143-60.

  6. Martinez FJ, Flaherty K. Pulmonary function testing in idiopathic interstitial pneumonias. Proc Am Thorac Soc. 2006 Jun. 3(4):315-21. [Medline]. [Full Text].

  7. Flaherty KR, Andrei AC, Murray S, et al. Idiopathic pulmonary fibrosis: prognostic value of changes in physiology and six-minute-walk test. Am J Respir Crit Care Med. 2006 Oct 1. 174(7):803-9. [Medline]. [Full Text].

  8. Misumi S, Lynch DA. Idiopathic pulmonary fibrosis/usual interstitial pneumonia: imaging diagnosis, spectrum of abnormalities, and temporal progression. Proc Am Thorac Soc. 2006 Jun. 3(4):307-14. [Medline].

  9. Orens JB, Estenne M, Arcasoy S, et al. International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant. 2006 Jul. 25(7):745-55. [Medline].

  10. American Thoracic Society/European Respiratory Society International Multidisciplinary Consensus Classification of the Idiopathic Interstitial Pneumonias. This joint statement of the American Thoracic Society (ATS), and the European Respiratory Society (ERS) was adopted by the ATS board of directors, June 2001 and by the ERS Executive Committee, June 2001. Am J Respir Crit Care Med. 2002 Jan 15. 165(2):277-304. [Medline].

  11. Harari S, Caminati A. IPF: new insight on pathogenesis and treatment. Allergy. 2010 May. 65(5):537-53. 

  12. Enzmann V, Lecaudé S, Kruschinski A, Vater A. CXCL12/SDF-1-dependent retinal migration of endogenous bone marrow-derived stem cells improves visual function after pharmacologically induced retinal degeneration. Stem Cell Rev. 2017;13:278–86. [PubMed] [Google Scholar]

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  17. Tzouvelekis A, Antoniadis A, Bouros D. Stem cell therapy in pulmonary fibrosis. Curr Opin Pulm Med. 2011;17:368–73.

  18. Srour N, Thébaud B. Mesenchymal Stromal Cells in Animal Bleomycin Pulmonary Fibrosis Models: A Systematic Review. Stem Cells Transl Med. 2015;4:1500–10. [PMC free article] [PubMed] [Google Scholar]

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  21. Zhao F, Zhang YF, Liu YG, Zhou JJ, Li ZK, Wu CG, Qi HW. Therapeutic effects of bone marrow-derived mesenchymal stem cells engraftment on bleomycin-induced lung injury in rats. Transplant Proc. 2008;40:1700–05. [PubMed] [Google Scholar]

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