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Stem Cell Therapy for Pulmonary Fibrosis

Introduction

Pulmonary fibrosis is a disease in which there is a pathological formation of scar tissue in the lungs so that they cannot fully perform their function to provide the body with oxygen. This condition significantly worsens the quality of life of the patient. In some cases, the progression of the disease may lead to lung and/or heart failure and death.

Modern medical drugs can’t reverse the pathological changes in lung fibrosis. Alternative methods of treating the pathology can include stem cell therapy for pulmonary fibrosis since their studied properties involve the ability to stop the inflammatory process, as well as to stimulate the recovery of damaged tissues.

About pulmonary fibrosis

Pulmonary fibrosis is associated with lung tissue scarring due to its fibrotic degeneration. The growth of scar tissue caused as a rule by inflammation, leads to compression of the alveoli, which can no longer fully perform their function, which is to ensure gas exchange in the body. Alveoli are the pulmonary vesicles in which inhaled air contacts the blood. Fibrotic lesions can affect a part of the lung or the entire organ, in one or both lungs.

Stem Cell Therapy for Pulmonary Fibrosis
Healthy lung tissue exchanges enough oxygen.

Pulmonary fibrosis, or pneumofibrosis, is a progressive illness with irreversible changes in lung tissue, whose complications and consequences include:

  1. Chronic respiratory failure (insufficient oxygen to the body).
  2. Pulmonary hypertension (high blood pressure in the pulmonary arteries).
  3. Chronic pulmonary heart and other cardiovascular diseases.
  4. Lung cancer
  5. Secondary respiratory infection (including the development of pneumonia with a high risk of death).

The causes of pulmonary fibrosis

It is not always possible to determine the exact reason that causes lung scarring. Pathological growth of connective tissue in the lungs may be provoked by allergies, lung infections, genetic factors, radiation, trauma, and other processes and circumstances.

When it is impossible to determine the exact cause of the pathology, we are talking about idiopathic pulmonary fibrosis (IPF). In such a disease, a combination of environmental exposure, genetic, and other unidentified factors is considered a provocateur.

Introduction to idiopathic pulmonary fibrosis.

There is also evidence that smoking (both in the present and the past), plus a burdened family history (noted in up to 20% of patients), plays a role. When at least two or more primary biological family members (parent, sibling, or child) have had clinical manifestations of IPF, the disease is classified as familial interstitial pneumonia (FIP). First-degree relatives of patients with FIP have a greatly increased risk of developing interstitial lung disease (ILD).

Interstitial pulmonary fibrosis

Interstitial lung disease (ILD), also known as diffuse parenchymal lung disease (DPLD), is a group of pathologies, including pulmonary fibrosis, in which the interstitial (connective tissue of the lung) is damaged. ILD is associated with inflammation and scarring of the lung tissue.

Interstitial tissue is the connective tissue of the lungs that serves as the backbone for the alveoli and blood vessels. In fibrosis, due to the excessive growth of connective tissue in the lung, alveoli are compressed and they are subsequently replaced with connective tissue. As a result, gas exchange in the alveoli becomes difficult, resulting in hypoxia – the body begins to suffer from a lack of oxygen.

Unlike idiopathic pulmonary fibrosis (IPF), the cause of ILD can be reliably determined. These reasons include:

  • infectious lesions;
  • autoimmune/connective tissue diseases;
  • genetic predisposition;
  • malignancies;
  • harmful inhaled substances (mercury vapor, mineral dust, etc); 
  • certain medications (for example, some antiarrhythmic drugs, nitrofurantoin, and others).

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Stem Cell Therapy for Pulmonary Fibrosis
Dr. Aleksandra Fetyukhina, MD

Medical Advisor, Swiss Medica doctor


Fibrosis developed due to coronavirus (COVID-19)

The coronavirus pandemic has increased the number of all cases of lung fibrosis. Now it is known that lung scarring is one of the most frequent and serious consequences of viral exposure in the human body. The mechanism of development of pulmonary fibrosis caused by COVID-19 is associated with an incorrect immune response, which leads to damage of lung epithelial cells and microvascular endothelial cells, especially in combination with artificial lung ventilation. 

Stem Cell Therapy for Pulmonary Fibrosis
Coronavirus is dangerous for its complications on the lung which include pulmonary fibrosis.

Moreover, according to researchers and statistical data, it becomes clear that patients with mild COVID-19 infection, even after improvement and discharge from the hospital, have a potential hidden risk of developing pulmonary fibrosis.

To prevent the progression of pulmonary fibrosis, induced by the coronavirus, it is essential to start the treatment of this complication as early as possible.

Signs & symptoms of pulmonary fibrosis

The clinical course of pulmonary fibrosis is associated with a decrease in lung volume, which forces the body to adapt to this negative consequence. Compensatory changes manifest as shortness of breath, which is the most frequent initial symptom reported by patients with IPF. At first, shortness of breath occurs only during physical exertion but later – also at rest.

The patient with IPF also faces symptoms such as: 

  • a dry cough
  • fatigue
  • unexplained weight loss

Also, clinical features of an underlying connective tissue disease (CTD), such as arthralgia (aching in several joints) or sicca symptoms (dryness of the exocrine glands, particularly the eyes, and mouth), might be observed.

The main external sign of IPF is known as ‘clubbed fingers’, which is a deformity of the fingers or toes characterized by enlargement of the tips of the digits. This symptom is associated with chronically low blood levels of oxygen.

The initial stages of the disease most often occur without manifestations. For example, in asymptomatic individuals at risk for familial interstitial pneumonia (FIP), signs of histologic changes in the lung tissue can be diagnostically identified.

Diagnosing pulmonary fibrosis

There is an opinion that lung fibrosis as a disease is insufficiently diagnosed. Most often, it is detected at a fairly late stage. Commonly, the disease is identified by an abnormality on a high-resolution computed tomography (HRCT) scan of the chest.

There is evidence that chest radiography is less useful than HRCT in evaluating patients with suspected IPF.

Bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy is also used to determine the condition of lung tissue.

Stem Cell Therapy for Pulmonary Fibrosis
Modern diagnostic methods help to detect fibrosis.

Also, laboratory diagnostics of various indicators (biological markers) can provide objectively measurable data about processes occurring in the body – both normal and pathological. In pulmonary fibrosis, these biomarkers help to diagnose the disease, reveal the disease susceptibility and predict specific drug efficacy. They can also accurately predict the course of the disease and its prognosis in a patient with IPF.

Traditional and modern treatments for ILD & lung fibrosis

While pulmonary fibrosis may take years to develop, most patients with the disease are diagnosed in its advanced stage, when little can be done to influence its progression. The existing treatments are aimed at maintaining the patient’s lung performance and an acceptable standard of living.

In the common method of treatment of pneumofibrosis, adrenal cortex hormones (prednisone) are used, and if they are not effective enough, azathioprine and cyclophosphane are used. Oxygen is also prescribed in inhalation. Recently, medications pirfenidone and nintedanib have been shown to slow IPF progression.

However, pulmonary fibrosis is a progressive disease and no antifibrotic agents or treatment (short of lung transplantation) are known to impact the poor survival rate associated with this disease.

Alternative methods of treating lung fibrosis and ILD include the use of stem cell for pulmonary fibrosis. 

Pathological changes occurring in the lungs with fibrosis are considered irreversible because the body has a poor ability to heal scar tissue. However, when we launch stem cells into the body in the amount of a therapeutic dose, this is often enough to start the regeneration processes and slow down the course of scarring of the lung tissue. For pulmonary fibrosis stem cell treatment, the cells can be injected either through an IV drip (intravenously) or by inhalation for targeted delivery of cells to the damaged area. 

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Stem Cell Therapy for Pulmonary Fibrosis
Dr. Aleksandra Fetyukhina, MD

Medical Advisor, Swiss Medica doctor


Stem cell therapy for pulmonary fibrosis

Cell-based therapy is known as a modern experimental treatment that uses the body’s ability to treat itself. Stem cell therapy for pulmonary fibrosis provides an opportunity to bypass the inadequacies of medical drugs.

How do infused stem cells act in fibrosis? The peculiarity of the ‘work’ of stem cells in the body is that they respond to signals sent by cells of damaged tissues, and produce cytokines (protein molecules that transmit intercellular signals) in response, which stimulate the formation of the new required cells.

Regarding stem cell research, pulmonary fibrosis is a disease of much interest. Studies of allogeneic (donor) mesenchymal stem cells (MSCs) have shown that they hone into sites of lung injury and contribute to tissue regeneration, decreasing chronic airway inflammation and restoration of alveolar fluid balance in acute lung injury.

Currently, further stem cell clinical trials for lung disease are being conducted.

What are the possible results after stem cell therapy?

Using stem cells for intravenous infusions in cellular therapy for pulmonary fibrosis, we can achieve the following effects:

  1. Slowing down or halting the scarring process, by ‘calming’ the patient’s immune system (stem cells have an anti-inflammatory ability).
  2. Partial regeneration of lung tissue.
  3. Formation of new vascular networks, which contribute to tissue renewal.
  4. Relief of the patient’s symptoms.

According to a clinical trial, endobronchial infusions of stem cell pulmonary fibrosis increased the number of indicators for quality of life. 86% of the participants of the study, who were observed for 12 months, demonstrated stable functional status and physical performance.

Thus, the main role of cellular therapy for pulmonary fibrosis, based on stem cell introduction, is slowing down the progression of the disease, stabilising lung function, and maintaining the current state of the patient.

Watch the video review of the patients with COPD (in Italian) to learn how stem cell therapy can help with lung disease: 

One more testimonial, for a patient who received stem cell treatment for idiopathic pulmonary fibrosis:

Stem Cell Treatment for Idiopathic pulmonary fibrosis (IPF).
It should be borne in mind that the amount of improvement in each patient may differ since it depends on several factors: the neglect of the disease, the presence of additional pathologies, the patient’s age, and the individual ‘response’ to stem cell treatment.

Safety of stem cells in pulmonary fibrosis

Сlinical trials of therapy, based on adult stem cells, demonstrated an acceptable safety profile of this approach. In particular, it was reported that during the entire period of a study using 72 infusions, no side effects were reported from stem cell therapy for pulmonary fibrosis that could be considered serious or clinically significant [19].

It is currently being debated whether MSCs can differentiate into fibroblasts, given their common mesodermal origin, and accelerate the fibrous cascade. However, there are no preclinical or human studies that have demonstrated this relationship.

None of the patients experienced any abnormal tissue formation, as reported by a whole-body CT scan performed 12 months after the first stem cell administration. The same positive safety result was obtained 24 months after the first infusion.

Another study demonstrates that infusions of stem cells were well-tolerated in all patients and no treatment-emergent serious adverse events were reported. This shows relative stem cell success with pulmonary fibrosis.

Where to treat pulmonary fibrosis

Most patients with pulmonary fibrosis have already been to a hospital to manage their condition. In most cases though, they see little improvement or desire a more effective means of treatment. This leads many to look for clinics where they can have cellular therapy for pulmonary fibrosis done.

Swiss Medica, in Belgrade, is one option for patients with pulmonary fibrosis, and with more than 20 years of experience, patients are assured of a treatment experience of the highest quality. The clinic has had stem cell success with pulmonary fibrosis on many occasions, which provides expertise in treating this particular condition.

What the treatment programme includes

The programme for stem cell treatment for pulmonary fibrosis at Swiss Medica can be broken down into broad stages.

The first thing that happens is the harvesting of mesenchymal stem cells from the patient’s body. You may have stem cells taken from your fat or bone marrow, though they may also be derived from donated tissues like umbilical cords or the placenta after a healthy delivery. 

After harvesting, these stem cells will be cultured to produce enough of them for therapeutic use. It can take as long as 4–8 weeks for these stem cells to be ready for treatment. To skip this stage and let the patient get the treatment immediately, donor cells are preferred.

With stem cell treatment for pulmonary fibrosis, the cells can be delivered into the patient’s body either through an intravenous infusion and/or directly through inhalation. Either way, the body will carry the stem cells to the damaged tissue, where they can begin to repair the damage.

Cost of stem cell therapy for pulmonary fibrosis

Generally speaking, stem cell treatment is costly. In most instances, it will cost several thousands of dollars, but the exact cost is highly dependent on the patient being treated. 

Factors that impact the pricing of stem cell treatment for pulmonary fibrosis include: 

  • the presence of comorbidities;
  • the severity of the condition;
  • whether other therapies might be needed;

and so on.

The best way to find out exactly how much to expect for treatment is to reach out to Swiss Medica for a free consultation, where all of your concerns can also be addressed.

Contact our medical advisor

Contact us to learn about the expected results of the therapy for your health condition, the treatment options, and its cost and duration.

Stem Cell Therapy for Pulmonary Fibrosis
Dr. Aleksandra Fetyukhina, MD

Medical Advisor, Swiss Medica doctor


List of References

  1. Study Links Pulmonary Fibrosis And Heart Disease. March 10, 2004. University Of California Los Angeles. Science News.

  2. Idiopathic Pulmonary Fibrosis and Lung Cancer: Mechanisms and Molecular Targets. Beatriz Ballester, Javier Milara, and Julio Cortijo. Int J Mol Sci. 2019 Feb; 20(3): 593.

  3. World Health Organisation. The top 10 causes of death. 24 May 2018.

  4. Risk factors for the development of idiopathic pulmonary fibrosis: A review. Tanzira Zaman and Joyce S. Lee. Curr Pulmonol Rep. 2018 Dec; 7(4): 118–125.

  5. Familial Interstitial Pneumonia (FIP). Janet L. Talbert, David A. Schwartz, and Mark P. Steele. Clin Pulm Med. 2014 May; 21(3): 120–127.

  6. ABCA3 mutations in adult pulmonary fibrosis patients: a case series and review of literature. Klay D, Platenburg MGJP, van Rijswijk RHNAJ, Grutters JC, van Moorsel CHM. Curr Opin Pulm Med. 2020 May;26(3):293-301.

  7. Interstitial Lung Disease Secondary to Long-Term Nitrofurantoin Use. Chin AJ, Rashid S, Gharibeh TR, Kibbe PS, Wynbrandt JH. Am J Case Rep. 2020 Apr 2;21:e920386.

  8. Advances in the research of mechanism of pulmonary fibrosis induced by Corona Virus Disease 2019 and the corresponding therapeutic measures. Wang J, Wang BJ, Yang JC, Wang MY, Chen C, Luo GX, He WF. Zhonghua Shao Shang Za Zhi. 2020 Mar 16;36(0):E006.

  9. Idiopathic Pulmonary Fibrosis: Diagnosis and Clinical Manifestations. Yutaro Nakamura and Takafumi Suda. Clin Med Insights Circ Respir Pulm Med. 2015; 9(Suppl 1): 163–171.

  10. Extensive Phenotyping of Individuals at Risk for Familial Interstitial Pneumonia Reveals Clues to the Pathogenesis of Interstitial Lung Disease. Jonathan A. Kropski,corresponding author Jason M. Pritchett,1 Donald F. Zoz,1,2 Peter F. Crossno,1,3 Cheryl Markin,1, and others. Am J Respir Crit Care Med. 2015 Feb 15; 191(4): 417–426.

  11. Idiopathic Pulmonary Fibrosis: A Genetic Disease That Involves Mucociliary Dysfunction of the Peripheral Airways. Christopher M. Evans, Tasha E. Fingerlin, Marvin I. Schwarz, David Lynch, Jonathan Kurche, and others. Physiol Rev. 2016 Oct; 96(4): 1567–1591.

  12. Extensive Phenotyping of Individuals at Risk for Familial Interstitial Pneumonia Reveals Clues to the Pathogenesis of Interstitial Lung Disease. Jonathan A. Kropski, Jason M. Pritchett, Donald F. Zoz, Peter F. Crossno, Cheryl Markin, and others. Am J Respir Crit Care Med. 2015 Feb 15; 191(4): 417–426.

  13. Biomarkers in idiopathic pulmonary fibrosis. Yingze Zhang and Naftali Kaminski. Curr Opin Pulm Med. 2012 Sep; 18(5): 441–446.

  14. Idiopathic Pulmonary Fibrosis: A Genetic Disease That Involves Mucociliary Dysfunction of the Peripheral Airways. Christopher M. Evans, Tasha E. Fingerlin, Marvin I. Schwarz, David Lynch, Jonathan Kurche, and others. Physiol Rev. 2016 Oct; 96(4): 1567–1591.

  15. Mesenchymal Stem Cells in Fibrotic Disease. El Agha E, Kramann R, Schneider RK, Li X, Seeger W, Humphreys BD, Bellusci S. Cell Stem Cell. 2017 Aug 3;21(2):166-177.

  16. Mesenchymal Stem Cell-Based Therapy of Inflammatory Lung Diseases: Current Understanding and Future Perspectives. C. Randall Harrell, Ruxana Sadikot, Jose Pascual, Crissy Fellabaum, Marina Gazdic Jankovic, and others. Stem Cells Int. 2019; 2019: 4236973.

  17. Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER). A Phase I Safety Clinical Trial. Marilyn K. Glassberg, Julia Minkiewicz, Rebecca L. Toonkel, Emmanuelle S. Simonet, Gustavo A. Rubio, and others. Chest. 2017 May; 151(5): 971–981.

  18. Mesenchymal Stem Cell as Therapeutic Modality in Interstitial Pulmonary Fibrosis. Clinical Trial.

  19. A prospective, non-randomized, no placebo-controlled, phase Ib clinical trial to study the safety of the adipose derived stromal cells-stromal vascular fraction in idiopathic pulmonary fibrosis. Argyris Tzouvelekis, Vassilis Paspaliaris, George Koliakos, Paschalis Ntolios, Evangelos Bouros, and others. J Transl Med. 2013; 11: 171.

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