Lung Disease
 

Chronic Obstructive Pulmonary Disease (COPD)

     Chronic obstructive pulmonary disease (COPD) is one of the most common lung diseases. It makes it difficult to breathe. There are two main forms of COPD: chronic bronchitis, which involves a long-term cough with mucus, and emphysema, which involves destruction of the lungs over time. Most people with COPD have a combination of both conditions. Smoking is the leading cause of COPD. Standard treatment includes the use of bronchodilator inhalers, steroids, and supplemental oxygen.

     Research has been ongoing around the world that exploits the anti-inflammatory and immuno-modulatory properties of adult stem cells to control the loss of elasticity and damage in the small airways seen in patients with COPD. Cell Surgical Network is investigating the effects of SVF (rich in mesenchymal stem cells and growth factors) on airway healing. We use a protocol that includes a combination of intravenous and nebulized SVF delivery. The deployment protocol performed under local anesthesia is all done as an outpatient at the time of SVF harvesting and procurement. The entire cellular surgical procedure takes approximately 3 hours.

    We care about our Chronic Obstructive Pulmonary Disease (COPD) patients at Cell Surgical Network and take pride in the time we provide to our patients to deploy the best protocols to help our patients achieve their goals. By filling out Confidential Candidate Application, we will answer the questions and concerns you may have about Cell Surgical Network protocols for Chronic Obstructive Pulmonary Disease (COPD).

 
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Cell Surgical Network Study for Stromal Vascular Fraction Registered by ClinicalTrials.gov

Rancho Mirage, CA (PRWEB) October 14, 2013

Clinicaltrials.gov, a service of the U.S. National Institutes of Health has registered on their public site an IRB approved safety study from the Cell Surgical Network, Inc.. This study is available for patients with various degenerative and inflammatory conditions to undergo Stromal Vascular Fraction deployment for the evaluation and for the advancement of future stem cell therapy procedures. Stromal Vascular Fraction is rich in autologous adipose derived stem cells and growth factors.

Stromal Vascular Fraction (SVF) is obtained by lipo-harvesting, procurement, and lipo-transfer as a same day operative procedure to provide therapy to patients with various degenerative and inflammatory diseases. Patients must be 16 years or older, male or female and have a degenerative disease or inflammatory disease that meets criteria for treatment under the IRB which includes: Arthritis, Auto-immune disease, COPD, Cardiomyopathy, Peyronies Disease, Interstitial Cystitis, Erectile Dysfunction, and Neurodegenerative disease such as Parkinson’s, ALS, Neuropathy. Patients must be healthy enough to tolerate a local anesthetic, must not have active cancer or infections.

Dr. Elliot Lander, and Dr. Mark Berman, founders of the Cell Surgical Network Inc. will conduct the study: “Ever since our inception, it’s been our goal to maintain transparency during our investigations. With a closed surgical procedure we can provide effective safety studies and evolve good empirical data that will allow us and others to ultimately refine our protocols,” says Dr. Berman.

The purpose of the safety study is to evaluate for any adverse effects that may be related to the administration and reception of autologous adipose derived stromal vascular fraction (SVF). Secondarily, the study monitors the results of subjective and objective findings as it applies to the non-blinded deployment of autologous SVF for various inflammatory and/or degenerative conditions including select orthopedic, neurologic, urologic and cardio-pulmonary conditions. SVF deployments include intra-venous, intra-articular, and soft tissue injections.

Outcome measures will include the number of participants with adverse events related to either SVF deployment or the lipo-harvesting procedure. Interested patients should contact the treatment center by phone: 800-231-0407 or via email: info(at)cellsurgicalnetwork(dot)com

About Cell Surgical Network:

The affiliates of the Cell Surgical Network (CSN) are devoted to advancing access and quality care in the area of adult stem cell regenerative medicine in order to help people suffering from a variety of inflammatory and degenerative conditions. The Cell Surgical Network was founded nearly two years after the formation of the California Stem Cell Treatment Center (founded in 2010). Affiliate members are generally made up of multi-state and international teams of multidisciplinary physicians in order to best assess and provide care for our patients. The Cell Surgical Network emphasizes quality and is highly committed to clinical research and the advancement of regenerative medicine.

 
Antimicrobial Properties of Mesenchymal Stem Cells: Therapeutic Potential for Cystic Fibrosis Infection, and Treatment.


Stem Cells Int. 2016;2016:5303048. doi: 10.1155/2016/5303048. Epub 2016 Jan 26.

Authors: Sutton MT, Fletcher D, Ghosh SK, Weinberg A, van Heeckeren R, Kaur S, Sadeghi Z, Hijaz A, Reese J, Lazarus HM, Lennon DP, Caplan AI, Bonfield TL.

 

Abstract
Cystic fibrosis (CF) is a genetic disease in which the battle between pulmonary infection and inflammation becomes the major cause of morbidity and mortality. We have previously shown that human MSCs (hMSCs) decrease inflammation and infection in the in vivo murine model of CF. The studies in this paper focus on the specificity of the hMSC antimicrobial effectiveness using Pseudomonas aeruginosa (gram negative bacteria) and Staphylococcus aureus (gram positive bacteria). Our studies show that hMSCs secrete bioactive molecules which are antimicrobial in vitro against Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumonia, impacting the rate of bacterial growth and transition into colony forming units regardless of the pathogen. Further, we show that the hMSCs have the capacity to enhance antibiotic sensitivity, improving the capacity to kill bacteria. We present data which suggests that the antimicrobial effectiveness is associated with the capacity to slow bacterial growth and the ability of the hMSCs to secrete the antimicrobial peptide LL-37. Lastly, our studies demonstrate that the tissue origin of the hMSCs (bone marrow or adipose tissue derived), the presence of functional cystic fibrosis transmembrane conductance regulator (CFTR: human, Cftr: mouse) activity, and response to effector cytokines can impact both hMSC phenotype and antimicrobial potency and efficacy. These studies demonstrate, the unique capacity of the hMSCs to manage different pathogens and the significance of their phenotype in both the antimicrobial and antibiotic enhancing activities.

 
Novel bronchoscopic treatment for bronchopleural fistula using adipose-derived stromal cells.


 Cytotherapy. 2016 Jan;18(1):36-40. doi: 10.1016/j.jcyt.2015.10.003. Epub 2015 Nov 6.

Authors: Díaz-Agero Álvarez PJ, Bellido-Reyes YA, Sánchez-Girón JG, García-Olmo D, García-Arranz M.

Abstract
 
BACKGROUND AIMS: In this report, we describe the successful bronchoscopic management of bronchopleural fistula in two patients, using autologous adipose-derived stromal cells. Cell therapy was considered for 2 cases of bronchopleural fistula refractory to conventional surgical treatment after control of the primary disease was confirmed and active pleural infection was ruled out. Briefly, adipose-derived stem cells were first isolated from lipoaspirate and used without cell expansion. In 24 months, we have not received more patients with bronchopleural fistula in our hospital and we have not been able to include more patients.

 

METHODS: Briefly, adipose-derived stem cells were first isolated from lipo-aspirate and used without cell expansion. A bronchopleural fistula was identified through bronchoscopy, and the mucosa surrounding the fistula was ablated with an argon plasma coagulator. Isolated stem cells were then endoscopically injected into the de-epithelialized area and fistulous tract. If an open thoracostomy was present at the time of the intervention, the same procedure was performed on the pleural side. Bronchoscopic follow-up was scheduled weekly during the first month, monthly during the first year, and then yearly. The underlying etiologies were left pneumonectomy and right lower video-assisted lobectomy for non-small-cell lung cancer. The sizes of the fistulas were 6 mm and 3 mm in diameter, respectively.

 

RESULTS: Both patients were discharged on the first postoperative day. The 3-year follow-up revealed a successful and maintained fistula closure, no treatment-related adverse reactions, nonlocal malignant recurrence and improved quality of life.
CONCLUSIONS: This preliminary study showed that bronchoscopic application of autologous adipose-derived stem cells is a feasible, safe and effective procedure for treating bronchopleural fistula.

 
Mesenchymal stem cells in the treatment of chronic lung disease.


Respirology. 2016 Nov;21(8):1366-1375. doi: 10.1111/resp.12911. Epub 2016 Sep 29.

Authors: Wecht S, Rojas M.

 

Abstract
 
Mesenchymal stem cells (MSCs) are a populace of non-haematopoietic multipotent stromal cells, which have the ability to differentiate into tissue derived from a single germ layer. MSCs have been isolated from various sites, including adipose tissue, skeletal muscle, synovium, spleen, thymus, lung and amniotic fluid, but are most often isolated from bone marrow. MSCs have several valuable functions that make them a promising therapeutic option in the field of regenerative medicine, including the secretion of anti-inflammatory cytokines and growth factors, the migration of cells to the site of injury when administered and the ability to 'rescue' cells through the transfer of functional mitochondria. They also offer the possibility of autologous cell transplantation, circumventing immune rejection. These properties, among others, make MSCs a promising potential therapeutic agent in the treatment of chronic lung diseases with high rates of morbidity and mortality, such as idiopathic pulmonary fibrosis (IPF), COPD and obstructive bronchiolitis (OB). Numerous animal models have shown the protective and reparative effects of MSCs in models of experimental lung injury. There are currently several clinical trials underway to evaluate the safety and efficacy of MSCs in the treatment of IPF, COPD and OB. While early results are encouraging, a considerable amount of research must be done concerning the safety MSCs, as well as their optimal dosage, time and route of administration. In addition, much is still unknown about the pathogenesis of these chronic lung diseases, as well as the mechanisms MSCs utilize to assist in their repair.

 

 
Fifty Years of Research in ARDS. Cell-based Therapy for Acute Respiratory Distress Syndrome. Biology and Potential Therapeutic Value.


 Am J Respir Crit Care Med. 2017 Aug 1;196(3):266-273. doi: 10.1164/rccm.201701-0107CP.

Authors: Laffey JG, Matthay MA.

Abstract
 
On the basis of several preclinical studies, cell-based therapy has emerged as a potential new therapeutic for acute respiratory distress syndrome (ARDS). Of the various cell-based therapy options, mesenchymal stem/stromal cells (MSCs) from bone marrow, adipose tissue, and umbilical cord have the most experimental data to support their potential efficacy for lung injury from both infectious and noninfectious causes. Mechanistically, MSCs exert their beneficial effects by release of paracrine factors, microvesicles, and transfer of mitochondria, all of which have antiinflammatory and pro-resolving effects on injured lung endothelium and alveolar epithelium, including enhancing the resolution of pulmonary edema by up-regulating sodium-dependent alveolar fluid clearance. MSCs also have antimicrobial effects mediated by release of antimicrobial factors and by up-regulating monocyte/macrophage phagocytosis. Phase 2a clinical trials to establish safety in ARDS are in progress, and two phase 1 trials did not report any serious adverse events. Several issues need further study, including: determining the optimal methods for large-scale production, reconstitution of cryopreserved cells for clinical use, defining cell potency assays, and determining the therapeutic potential of conditioned media derived from MSCs. Because ARDS is a heterogeneous syndrome, targeting MSCs to patients with ARDS with a more hyperinflammatory endotype may further enhance their potential for efficacy.

 

Adipose-Derived Mesenchymal Stem Cells for Treatment of Airway Injuries in A Patient after Long-Term Exposure to Sulfur Mustard.
 


Cell J. 2017 Apr-Jun;19(1):117-126. Epub 2016 Dec 21.

Authors:Nejad-Moghaddam A, Ajdari S, Tahmasbpour E, Goodarzi H, Panahi Y, Ghanei M.

Abstract

 

OBJECTIVE: Sulfur mustard (SM) is a potent mutagenic agent that targets several organs, particularly lung tissue. Changes in morphological structure of the airway system are associated with chronic obstructive pulmonary deficiency following exposure to SM. Although numerous studies have demonstrated pathological effects of SM on respiratory organs, unfortunately there is no effective treatment to inhibit further respiratory injuries or induce repair in these patients. Due to the extensive progress and achievements in stem cell therapy, we have aimed to evaluate safety and potential efficacy of systemic mesenchymal stem cell (MSC) administration on a SM-exposed patient with chronic lung injuries.

 

MATERIALS AND METHODS: In this clinical trial study, our patient received 100×106cells every 20 days for 4 injections over a 2-month period. After each injection we evaluated the safety, pulmonary function tests (PFT), chronic obstructive pulmonary disease (COPD) Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), Borg Scale Dyspnea Assessment (BSDA), and 6 Minute Walk Test (6MWT). One-way ANOVA test was used in this study which was not significant (P>0.05).

 

RESULTS: There were no infusion toxicities or serious adverse events caused by MSC administration. Although there was no significant difference in PFTs, we found a significant improvement for 6MWT, as well as BSDA, SGRQ, and CAT scores after each injection.
CONCLUSION: Systemic MSC administration appears to be safe in SM-exposed patients with moderate to severe injuries and provides a basis for subsequent cell therapy investigations in other patients with this disorder.

 

 Autologous Stromal Vascular Fraction in the Intravenous Treatment of End-Stage Chronic Obstructive Pulmonary Disease: A Phase I Trial of Safety and Tolerability.
 


J Clin Med Res. 2017 Aug;9(8):701-708. doi: 10.14740/jocmr3072w. Epub 2017 Jul 1.

Authors: Comella K, Blas JAP, Ichim T, Lopez J, Limon J, Moreno RC.

 Abstract
 
Chronic obstructive pulmonary disease (COPD) is a consistently progressive, ultimately fatal disease for which no treatment exists capable of either reversing or even interrupting its course. It afflicts more than 5% of the population in many countries, and it accordingly represents the third most frequent cause of death in the US, where it accounts for more than 600 billion in health care costs, morbidity, and mortality. Adipose tissue contains within its stromal compartment a high abundance of adipose stem/stromal cells (ASCs), which can be readily separated from the adipocyte population by methods which require less than 2 h of processing time and yield a concentrated cellular preparation termed the stromal vascular fraction (SVF). The SVF contains all cellular elements of fat, excluding adipocytes. Recent clinical studies have begun to explore the feasibility and safety of the local injection or intravascular delivery of SVF or more purified populations of ASCs derived by culture protocols. Several pre-clinical studies have demonstrated a remarkable ability of ASC to nearly fully ameliorate the progress of emphysema due to cigarette smoke exposure as well as other causes. However, no prior clinical studies have evaluated the safety of administration of either ASC or SVF in subjects with COPD. We hypothesized that harvest, isolation, and immediate intravenous infusion of autologous SVF would be feasible and safe in subjects with COPD; and that such an approach, if ultimately determined to be efficacious as well as safe, would provide a highly practical method for treatment of COPD. In this study, an initial phase I trial evaluating the early and delayed safety of SVF infusion was performed. Twelve subjects were enrolled in the study, in which adipose tissue was harvested using standard liposuction techniques, followed by SVF isolation and intravenous infusion of 150 - 300 million cells. Standardized questionnaires were administered to study feasibility as well as immediate and delayed outcomes and adverse events as primary endpoints. Secondary endpoints included subjective wellness and attitudes towards the procedure, as well as willingness to undergo the procedure a second time. The follow-up time ranged from 3 to 12 months, averaging 12 months.
 
RESULTS:  Of the 12 subjects, only one experienced an immediate adverse event, related to bruising from the liposuction. No observed pulmonary or cardiac issues were observed as related to the procedure. There were no deaths over the 12-month study period, and none identified in the subsequent telephonic follow-up. Attitudes toward the procedure were predominantly positive, and 92% of the study subjects expressed a desire to undergo the procedure a second time.

CONCLUSIONS: This study is the first to demonstrate safety of SVF infusion in humans with serious pulmonary disease. Specifically, the use of intravenous infusion as a route to achieve pulmonary cellular targeting did not lead to clinical pulmonary compromise. The intravenous administration of SVF should be further explored as a potentially feasible and safe method for delivery leading to possible therapeutic benefit.

 
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