LUNG DISEASE – COPD
There has been some very good clinical results using adult stem cells for lung conditions. Below are published peer-reviewed clinical journal articles that prove beneficial outcomes using these technologies. Also, below is reports of COPD patients that have had the treatment and it shows before and after lung function tests. This treatment is now available in Bangkok, Thailand.

This stem cell therapy can be used for lung conditions such as Chronic Obstructive Pulmonary Disease, COPD, and Idiopathic Pulmonary Fibrosis or IPF. Contact us if you have lung disease and would like a doctor’s opinion.

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Below is published peer reviewed research on using adult stem cells to treat lung disease.

Chest. 2013 Jun;143(6):1590-1598. doi: 10.1378/chest.12-2094.

A placebo-controlled, randomized trial of mesenchymal stem cells in COPD.

 

Weiss DJ1, Casaburi R2, Flannery R3, LeRoux-Williams M3, Tashkin DP4.

Author information
1- Vermont Lung Center, University of Vermont College of Medicine, Burlington, VT. Electronic address: dweiss@uvm.edu.
2- Los Angeles Biomedical Research Institute, Harbor-University of California, Los Angeles (UCLA) Medical Center, Torrance, CA.
3- Osiris Therapeutics Inc, Columbia, MD.
4- David Geffen School of Medicine, UCLA, Los Angeles, CA.

BACKGROUND:
COPD is a devastating disease affecting millions worldwide. As disease pathogenesis includes both chronic pulmonary and systemic inflammation, antiinflammatory effects of systemically administered mesenchymal stem cells (MSCs) may decrease inflammation, resulting in improved lung function and quality of life. The goal of this study was to assess safety and to perform an initial evaluation of the potential efficacy of systemic MSC administration to patients with moderate to severe COPD.

METHODS:
Sixty-two patients at six sites were randomized to double-blinded IV infusions of either allogeneic MSCs (Prochymal; Osiris Therapeutics Inc) or vehicle control. Patients received four monthly infusions (100 × 10⁶ cells/infusion) and were subsequently followed for 2 years after the first infusion. End points included comprehensive safety evaluation, pulmonary function testing (PFT), and quality-of-life indicators including questionnaires, 6MWT, and assessments of systemic inflammation.

RESULTS:
All study patients completed the full infusion protocol, and 74% completed the 2-year follow-up. There were no infusional toxicities and no deaths or serious adverse events deemed related to MSC administration. There were no significant differences in the overall number of adverse events, frequency of COPD exacerbations, or worsening of disease in patients treated with MSCs. There were no significant differences in PFTs or quality-of-life indicators; however, an early, significant decrease in levels of circulating C-reactive protein (CRP) was observed in patients treated with MSCs who had elevated CRP levels at study entry.

CONCLUSIONS:
Systemic MSC administration appears to be safe in patients with moderate to severe COPD and provides a basis for subsequent cell therapy investigations.

TRIAL REGISTRY:
ClinicalTrials.gov; No.: NCT00683722; URL: www.clinicaltrials.gov.


Curr Opin Pharmacol. 2009 Jun;9(3):268-73. doi: 10.1016/j.coph.2009.03.002. Epub 2009 Apr 6.

Cell therapy approaches for lung diseases: current status.

 

Sueblinvong V1, Weiss DJ.

Abstract
Recent findings suggest that embryonic stem cells and stem cells derived from adult tissues, including bone marrow and umbilical cord blood, could be utilized in repair and regeneration of injured or diseased lungs. This is an exciting and rapidly moving field that holds promise as a therapeutic approach for variety of lung diseases. Although initial emphasis was on engraftment of stem cells in lung, more recent studies demonstrate that mesenchymal stem cells (MSCs) can modulate local inflammatory and immune responses in mouse lung disease models including acute lung injury and pulmonary fibrosis. Further, on the basis of initial reports of safety and efficacy following allogeneic administration of MSCs to patients with Crohn’s disease or with graft-versus-host disease, a recent trial has been initiated to study the effect of MSCs in patients with chronic obstructive pulmonary disease. Notably, several recent clinical trials have demonstrated potential benefit of autologous stem cell administration in patient with pulmonary hypertension. In this review, we will describe recent advances in cell therapy with the focus on MSCs and their potential roles in lung development and repair.

PMID: 19349209 PMCID: PMC4201364 DOI: 10.1016/j.coph.2009.03.002

Stem cell therapy for idiopathic pulmonary fibrosis: a protocol proposal

Argyris Tzouvelekis1, George Koliakos2, Paschalis Ntolios3, Irene Baira3, Evangelos Bouros3, Anastasia Oikonomou4, Athanassios Zissimopoulos5, George Kolios3,Despoina Kakagia6, Vassilis Paspaliaris7, Ioannis Kotsianidis8, Marios Froudarakis1and Demosthenes Bouros1*

VIEW ABSTRACT

Background

Idiopathic pulmonary fibrosis represents a lethal form of progressive fibrotic lung disorder with gradually increasing incidence worldwide. Despite intense research efforts its pathogenesis is still elusive and controversial reflecting in the current disappointing status regarding its treatment. Patients and Methods: We report the first protocol proposal of a prospective, unicentric, non-randomized, phase Ib clinical trial to study the safety and tolerability of the adipose-derived stem cells (ADSCs) stromal vascular fraction (SVF) as a therapeutic agent in IPF. After careful patient selection based on functional criteria (forced vital capacity-FVC > 50%, diffuse lung capacity for carbon monoxide-DLCO > 35% of the predicted values) all eligible subjects will be subjected to lipoaspiration resulting in the isolation of approximately 100- 500 gr of adipose tissue. After preparation, isolation and labelling ADSCs-SVF will be endobronchially infused to both lower lobes of the fibrotic lungs. Procedure will be repeated thrice at monthly intervals. Primary end-point represent safety and tolerability data, while exploratory secondary end-points include assessment of clinical functional and radiological status. Results: Preliminary results recently presented in the form of an abstract seem promising and tantalizing since there were no cases of clinically significant allergic reactions, infections, disease acute exacerbations or ectopic tissue formation. In addition 6 months follow-up data revealed a marginal improvement at 6-minute walking distance and forced vital capacity.

Conclusions

Adipose tissue represents an abundant, safe, ethically uncontested and potentially beneficial source of stem cells for patients with IPF. Larger multicenter phase II and III placebo-controlled clinical trials are sorely needed in order to prove efficacy. However, pilot safety studies are of major importance and represent the first hamper that should be overcome to establish a rigid basis for larger clinical trials.

Keywords:
stem cells; adipose tissue; stromal vascular fraction; idiopathic pulmonary fibrosis; therapy; endobronchial infusion; prospective; nonrandomized phase Ib clinical trial

Journal of Translational
Medicine.
http://www.translational-medicine.com/content/9/1/182

J Transl Med. 2011 Jul 22;9(1):118. [Epub ahead of print]

Autologous Transplantation of Adipose-Derived Mesenchymal Stem Cells Markedly Reduced Acute Ischemia – Reperfusion Lung Injury in a Rodent Model.
Sun CK, Yen CH, Lin YC, Tsai TH, Chang LT, Kao YH, Chua S, Fu M, Ko SF, Leu S, Yip HK.

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ABSTRACT: BACKGROUND: This study tested the hypothesis that autologous transplantation of adipose-derived mesenchymal stem cells (ADMSCs) can effectively attenuate acute pulmonary ischemia-reperfusion (IT) injury. METHODS: Adult make Sprague-Dawley (SD) rats (n=24) were equally randomized into group 1 (sham control), group 2 (IR plus culture medium only), and group 3 (IR plus intravenous transplantation of autologous ADMSCs at 30 minute, 6h, 24h following IT injury). The duration of ischemia was 30 minutes, followed by 72 hours of reperfusion prior to sacrificing the animals. Blood samples were collected and lungs were harvested for analysis.

RESULTS: Blood gas analysis showed that oxygen saturation (%) was remarkably lower, whereas right ventricular systolic pressure was notably higher in group 2 than in group 3 (all p < 0.03). Histological scoring of lung parenchymal damage was notably higher in group 2 than group3 (all p < 0 005). Real time-PCR demonstrated remarkably higher expressions of oxidative stress, as well as flammatory and adoptotic biomarkers in group 2 compared with group 3 ((all p < 0005). Western blot showed that vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, oxidative stress, tumor necrosis factor-alpha and nuclear factor-kappaB were remarkably higher, whereas NAD (P) H quinine oxidoreductase 1 and heme oxygenase-1 activities were lower in group 2 compared to those in group 3 (all p< 0.004). Immunoflourecent staining demonstrated notably higher number of CD68+ cells, but significantly fewer DC31+ and VWF+ cells in group 2 than in group 3.

CONCLUSION: ADMSC therapy minimized lung damage after IR injury in a rodent model through suppressing oxidate stress and inflammatory reaction.

PMID: 21781312 [PubMed - as supplied by publisher] Free full text

Background on Lung Trial

AdiStem conducted its first clinical trial using Adipose-derived stem cells in 2006 on Type II diabetes. After safety and efficacy were proven, more trials were undertaken in 2008. Case studies showed improvements in lung condition and pulmonary function as reported by physicians. As a result of this clinical evidence, particularly with COPD patients, AdiStem partnered with Democritus University to conduct a formal, ethics-approved clinical trial for Idiopathic Pulmonary Fibrosis in the EU. The principle investigator is Professor Bouros along with his colleagues. Below is an abstract summary, information on tagging and tracing autologous stem cells to the lungs and how photomodulation helps activate adipose stem cells prior to treatment.

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A prospective, non randomized, clinical trial to study the safety and efficacy of the endobronchial autologous infusion of adipose-derived mesenchymal stem cells (ADMSCs) in patients with idiopathic pulmonary fibrosis (IPF).

Argyris Tzouvelekis1, Paschalis Ntolios1, Anastasia Oikonomou2, George Koliakos3, Vassilis Paspaliaris3, Marios Froudarakis1, Demosthenes Bouros1.

1. Department of Pneumonology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece

2. Department of Radiology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece

3. Department of Biochemistry, Aristotles University of Thessaloniki, Thessaloniki, Greece

Correspondence Demosthenes Bouros MD, PhD, FCCP Professor of Pneumonology Head, Department of Pneumonology, University Hospital of Alexandroupolis, Greece 68100

Background: Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and lethal fibrotic lung disease of unknown etiology and treatment yet ineffective. The aim of the study was to investigate the safety and efficacy of endobronchial autologous infusion of adipose-derived mesenchymal stem cells (ADMSCs) in patients with IPF.

Methods: We performed a prospective, non-randomized trial of endobronchial autologous ADMSCs in IPF patients who met ATS/ERS 2000 criteria with mild to moderate lung disease as assessed by Forced vital capacity (FVC) >50% and diffusion capacity of the lung for carbon monoxide (DLCO) >30%. All eligible patients (n=12) underwent lipoaspiration and ADMSCs were isolated using a standard protocol provided by Adistem Ltd. The primary end point was incidence of treatment-emergent adverse events within 6 months after first infusion. FVC, DLCO and 6-minute walking distance (6MWD), were exploratory efficacy end points.

Results: No cases of clinically significant allergic reactions, disease acute exacerbation or infection were recorded in all patients. There were no significant alterations in FVC and DLCO 6 months post-treatment, though an almost marginal trend towards improvement in 6MWD (p=0.07) was reported.

Conclusions: This ongoing clinical trial provides pivotal safety and provisional efficacy data for endobronchial autologous infusion of ADMSCs in patients with IPF. Larger studies are sorely needed.

Reference: European Respiratory Society

Medical University Conducting Trial

Democritus University of Thrace SCHOOL OF MEDICINE University Hospital of Alexandroupolis

The Medical School of the Democritus University of Thrace was established in 1977 with the aim of becoming a modern teaching center committed to excellence in the education and training of students, physicians and biomedical scholars. It was named after the great ancient Greek philosopher Demokritos (460-370 BC) who was born in Avdera, Thrace, an administrative district of Greece.

Since 2003, The School of Medicine operates on its new campus, located about 7 km from Alexandroupolis, representing one of the newest medical and research complexes in Greece. The campus includes The University Hospital of Alexandroupolis, one of the largest of the country, with a capacity of 700 beds.

The Department of Pneumonology of the Democritus University of Thrace was established in 1987. Since October 2002, director of the department is Prof. D. Bouros, and in the new building of the University Hospital of Alexandroupolis, the department has 4 academic members, 2 consultants and 7 residents. The residents are given full specialization after 5 years of clinical practice in the department.

The department is a referral center for the Interstitial Lung Diseases and a center of excellence in Pulmonary Fibrosis. There is also a special interest in interventional pulmonology with hands-on yearly seminars in medical thoracoscopy.

Photoactivation

AdiStem Ltd. has been researching the effect of different monochromatic light intensities and frequencies in the colored spectrum on various human and animal cell populations such as mesenchyme stem cells and white blood cells.

Low-level light photoactivation or photomodulation can be utilized for significant benefit in the stimulation of proliferation, differentiation, and inhibition/induction release of growth factors/cytokines of cells from any living organism.

The wavelength or bandwidth of wavelengths is one of the critical factors in selective photomodulation. Pulsed or continuous exposure, duration and frequency of pulses (and dark ‘off’ period) and energy are also factors as well as the presence, absence or deficiency of any or all cofactors, enzymes, catalysts, or other building blocks of the process being photomodulated.

Different parameters with the same wavelength may have very diverse and even opposite effects. When different parameters of photomodulation are performed simultaneously, different effects may be produced. When different parameters are used serially or sequentially, the effects are also different.

The selection of wavelength photomodulation is critical as is the bandwidth selected as there may be a very narrow bandwidth for some applications — in essence these are biologically active spectral intervals. Generally the photomodulation will target flavins, cytochromes, iron-sulfur complexes, quinines, heme, enzymes, and other transition metal ligand bond structures though not limited to these.

Tagging and tracking stem cells in the lungs

The following image shows TC99 tagging of activated stem cells. These is a similar technique used for Rheumatoid Arthritis tagging of white blood cells. Activated adipose derived stem cells were tagged with TC99 and given to an IPF patient. Twenty four hours later a full body scan was taken of the patient. It is clear the autologous ( from the patient ) activated stem cells were found in the lung tissue of the patient. Here it is believed they secrete growth factors and signal resident stem cells to proliferate and regenerate damaged tissue.

gamma-camera-scan

Anal Chem. 2011 Sep 29. [Epub ahead of print]

Estimation of the Distribution of Intravenously Injected Adipose Tissue-Derived Stem Cells Labeled with Quantum Dots in Mice Organs through the Determination of their Metallic Components by ICP-MS.
Takasaki YWatanabe MYukawa HSabarudin AInagaki KKaji NOkamoto YTokeshi M,Miyamoto YNoguchi HUmemura THayashi SBaba YHaraguchi H.

VIEW ABSTRACT

Adipose tissue-derived stem cells (ASCs) have shown promise in cell therapy because of their ability to self-renew damaged or diseased organs and easy harvest. To ensure the distribution and quantification of the ASCs injected from tail vein, several whole-body imaging techniques including fluorescence optical imaging with quantum dots (QDs) have been employed, but they may suffer from insufficient sensitivity and accuracy. Here, we report quantitative distribution of ASCs in various organs (heart, lung, liver, spleen, and kidney) of mice, which were intravenously injected with QDs-labeled ASCs (QDs-ASCs), through the detection of QDs-derived metallic components by inductively coupled plasma mass spectrometry (ICP-MS). For accurate and precise determination, each organ was harvested and completely digested with a mixture of HNO3 and H2O2 in a microwave oven prior to ICP-MS measurement, which was equipped with a micro flow injection system and a laboratory-made capillary-attached micronebulizer. After optimization, 16 elements including major components (Cd, Se, and Te) of QDs and essential elements (Na, K, Mg, Ca, P, S, Mn, Fe, Co, Cu, Zn, Se, Sr, and Mo) were successfully determined in the organs. As compared to untreated mice, QDs-ASCs-treated mice showed significantly higher levels of Cd and Te in all organs, and as expected, the molar ratio of Cd to Te in each organ was in good agreement with the molar composition ratio in the QDs. This result indicates that the increment of Cd (or Te) can be used as a tracer for calculating the distribution of ASCs in mice organs. As a result of the calculation, 36.8%, 19.1%, 0.59%, 0.49%, and 0.25% of the total ASCs injected were estimated to be distributed in the liver, lung, heart, spleen, and kidney, respectively.

PMID: 21958307

[PubMed - as supplied by publisher]

Link to PubMed;
http://www.ncbi.nlm.nih.gov/pubmed/21958307

Stem cell therapy for idiopathic pulmonary fibrosis: a protocol proposal

Background

The following is a Peer Reviewed, Published Clinical Trial on Idiopathic Pulmonary Fibrosis and the use of Autologous Adipose Derived Stem Cells applied systemically. The research was conducted under Institutional Review Board and University Ethics Approval in the European Union. Patient improvement for this lung disease is discussed.

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