Safety and Potential Efficacy of Human Mesenchymal Stem Cells in Non‐Cystic Fibrosis Bronchiectasis

Bronchiectasis Clinical Trial

— CELEB  

Official title:

A Phase I, Trial to Evaluate the Safety, Tolerability, and Potential Efficacy of Allogeneic Human Mesenchymal Stem Cell (hMSC) Infusion in Patients With Non-Cystic Fibrosis Bronchiectasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02625246
• Other study ID #: 20150627
• Status: Completed
• Phase: Phase 1
• Start date: February 4, 2016
• Est. completion date: May 15, 2019

Study information

• Verified date: August 2019
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To demonstrate the safety of bone marrow-derived allogeneic human Mesenchymal Stem Cells (hMSCs) in patients with bronchiectasis receiving standard of care therapy, and to explore treatment efficacy

Description:

A Phase 1 investigation will be performed to test the safety of two doses of bone-marrow derived hMSCs (20,000,000 and 100,000,000) administered via peripheral intravenous infusion.

Group 1: 3 subjects will receive a single administration of allogeneic hMSCs: 20 x106 (20 million) cells delivered via peripheral intravenous infusion Group 2: 3 subjects will receive a single administration of allogeneic hMSCs: 1 x108 (100 million) cells delivered via peripheral intravenous infusion Interim safety analysis will be performed four weeks after the 1st subject is enrolled in each cohort. Continued safety and tolerability with review of adverse events (AEs) will be assessed at each visit. Efficacy parameters (pulmonary function tests, lung diffusion capacity, lung volumes, 6-Minute Walk Test (6MWT), and dyspnea/Quality of Life (QOL) questionnaires) will be assessed every 12 weeks until study completion. Clinical laboratory tests to assess safety will be performed at every visit.

High Resolution Computed Tomography (HRCT) scan will be performed at the baseline visit (if not done within three months prior to enrollment) and then at week 24.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: May 15, 2019
• Est. primary completion date: May 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 87 Years

Eligibility

Inclusion Criteria:

• Provide written informed consent,

• be between 30 and 87 years old at the time of signing the Informed Consent,

• weight over 45 and under 150 kg,

• have a clinical diagnosis of non-CF bronchiectasis prior to screening,

• Have had at least 2 exacerbations in the past year as documented by physician office or hospital visits (Use of antibiotics of at least one time in the last year),

• Show a baseline FEV1 between 25% and 85% predicted and over or equal to 1 L and a baseline diffusion capacity of lung for carbon monoxide (DLCO) over or equal to 30% (corrected for hemoglobin but not alveolar volume),

• Have a normal Right Ventricular function, as documented by Doppler echo or right heart catheterization,

• if a female of childbearing potential, agree to abide by contraception rules defined below.

• Subjects may receive nondrug therapies including oxygen supplementation not greater than 4 Liters per minute and pulmonary rehabilitation.

• Subjects may be on chronic macrolide or inhaled antibiotic treatment bronchiectasis

Exclusion Criteria:

• Have HRCT and or surgical lung biopsy results inconsistent with the diagnosis of non-CF bronchiectasis. (Exclusion of emphysema and or diffuse parenchymal disease)

• be unable to perform any of the assessments required for endpoint analysis (report safety or tolerability concerns, perform Pulmonary Function Tests (PFT) or HRCT, undergo blood draws, read and respond to questionnaire

• If a female of childbearing potential, have a follicle stimulating hormone (FSH) under 25.8 IU/L

• be actively treated for an acute infectious exacerbation of bronchiectasis

• Have an active infection that is not treated

• Have had active infections occurring within a minimum of 4 weeks of study treatment

• Be currently on treatment for NTM infections

• Have had positive sputum cultures for nontuberculous mycobacterial (NTM) within the past 6 months

• Have a history of drug or alcohol abuse within the past 24 months.

• Be currently receiving (or have received within four weeks of screening) experimental agents for the treatment of bronchiectasis or have been enrolled in clinical trials within the previous 30 days

• Be actively listed (or expect future listing) for transplant of any organ.

• Have clinically important abnormal screening laboratory values.

• Have a serious comorbid illness that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study.

• Have any other condition that, in the opinion of the investigator, may compromise the safety or compliance of the patient or preclude successful completion of the study.

• Have known allergies to penicillin or streptomycin.

• Be an organ transplant recipient.

• Have a clinical history of malignancy within 5 years (i.e., patients with prior malignancy must be disease free for 5 years), except curatively-treated basal cell carcinoma of skin, squamous cell carcinoma of skin, or cervical carcinoma.

• Have a non-pulmonary condition that limits lifespan to less than 1 year.

• Be serum positive for HIV, hepatitis BsAg (surface agent reactive) or Viremic hepatitis C.

• Have hypersensitivity to dimethyl sulfoxide (DMSO)

• Be unable to maintain saturated oxygen (SpO2) of more than 93% on room air at sea level at rest) or an SpO2 of more than 88% on room air over 5,000 feet (1524 meters) above sea level at rest.

Related Conditions & MeSH terms

• Bronchiectasis

Intervention

Biological:
• hMSCs
intravenous infusion of bone marrow-derived allogeneic stem cells

Locations

Country	Name	City	State
United States	University of Miami Hospitals & Clinics	Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Marilyn Glassberg

Country where clinical trial is conducted

United States, 

References & Publications (63)

Altenburg J, de Graaff CS, Stienstra Y, Sloos JH, van Haren EH, Koppers RJ, van der Werf TS, Boersma WG. Effect of azithromycin maintenance treatment on infectious exacerbations among patients with non-cystic fibrosis bronchiectasis: the BAT randomized controlled trial. JAMA. 2013 Mar 27;309(12):1251-9. doi: 10.1001/jama.2013.1937. — View Citation

Antoniou KM, Papadaki HA, Soufla G, Kastrinaki MC, Damianaki A, Koutala H, Spandidos DA, Siafakas NM. Investigation of bone marrow mesenchymal stem cells (BM MSCs) involvement in Idiopathic Pulmonary Fibrosis (IPF). Respir Med. 2010 Oct;104(10):1535-42. doi: 10.1016/j.rmed.2010.04.015. Epub 2010 May 18. — View Citation

Bilton D, Tino G, Barker AF, Chambers DC, De Soyza A, Dupont LJ, O'Dochartaigh C, van Haren EH, Vidal LO, Welte T, Fox HG, Wu J, Charlton B; B-305 Study Investigators. Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial. Thorax. 2014 Dec;69(12):1073-9. doi: 10.1136/thoraxjnl-2014-205587. Epub 2014 Sep 21. — View Citation

Bitencourt CS, Pereira PA, Ramos SG, Sampaio SV, Arantes EC, Aronoff DM, Faccioli LH. Hyaluronidase recruits mesenchymal-like cells to the lung and ameliorates fibrosis. Fibrogenesis Tissue Repair. 2011 Jan 13;4(1):3. doi: 10.1186/1755-1536-4-3. — View Citation

Bonfield TL, Koloze M, Lennon DP, Zuchowski B, Yang SE, Caplan AI. Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. Am J Physiol Lung Cell Mol Physiol. 2010 Dec;299(6):L760-70. doi: 10.1152/ajplung.00182.2009. Epub 2010 Sep 3. — View Citation

Cargnoni A, Gibelli L, Tosini A, Signoroni PB, Nassuato C, Arienti D, Lombardi G, Albertini A, Wengler GS, Parolini O. Transplantation of allogeneic and xenogeneic placenta-derived cells reduces bleomycin-induced lung fibrosis. Cell Transplant. 2009;18(4):405-22. doi: 10.3727/096368909788809857. — View Citation

Chambers DC, Enever D, Ilic N, Sparks L, Whitelaw K, Ayres J, Yerkovich ST, Khalil D, Atkinson KM, Hopkins PM. A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis. Respirology. 2014 Oct;19(7):1013-8. doi: 10.1111/resp.12343. Epub 2014 Jul 9. — View Citation

Chang JC, Summer R, Sun X, Fitzsimmons K, Fine A. Evidence that bone marrow cells do not contribute to the alveolar epithelium. Am J Respir Cell Mol Biol. 2005 Oct;33(4):335-42. Epub 2005 Jun 16. — View Citation

Deans RJ, Moseley AB. Mesenchymal stem cells: biology and potential clinical uses. Exp Hematol. 2000 Aug;28(8):875-84. Review. — View Citation

Fang X, Neyrinck AP, Matthay MA, Lee JW. Allogeneic human mesenchymal stem cells restore epithelial protein permeability in cultured human alveolar type II cells by secretion of angiopoietin-1. J Biol Chem. 2010 Aug 20;285(34):26211-22. doi: 10.1074/jbc.M110.119917. Epub 2010 Jun 16. — View Citation

Gao J, Dennis JE, Muzic RF, Lundberg M, Caplan AI. The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. Cells Tissues Organs. 2001;169(1):12-20. — View Citation

Glassberg MK, Toonkel RL. Moving stem cell therapy to patients with idiopathic pulmonary fibrosis. Respirology. 2014 Oct;19(7):950-1. doi: 10.1111/resp.12364. Epub 2014 Aug 14. — View Citation

Gong Z, Niklason LE. Use of human mesenchymal stem cells as alternative source of smooth muscle cells in vessel engineering. Methods Mol Biol. 2011;698:279-94. doi: 10.1007/978-1-60761-999-4_21. — View Citation

Gupta N, Krasnodembskaya A, Kapetanaki M, Mouded M, Tan X, Serikov V, Matthay MA. Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax. 2012 Jun;67(6):533-9. doi: 10.1136/thoraxjnl-2011-201176. Epub 2012 Jan 16. — View Citation

Gupta N, Su X, Popov B, Lee JW, Serikov V, Matthay MA. Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol. 2007 Aug 1;179(3):1855-63. — View Citation

Hare JM, Fishman JE, Gerstenblith G, DiFede Velazquez DL, Zambrano JP, Suncion VY, Tracy M, Ghersin E, Johnston PV, Brinker JA, Breton E, Davis-Sproul J, Schulman IH, Byrnes J, Mendizabal AM, Lowery MH, Rouy D, Altman P, Wong Po Foo C, Ruiz P, Amador A, Da Silva J, McNiece IK, Heldman AW, George R, Lardo A. Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy: the POSEIDON randomized trial. JAMA. 2012 Dec 12;308(22):2369-79. Erratum in: JAMA. 2013 Aug 21;310(7):750. George, Richard [added]; Lardo, Albert [added]. — View Citation

Hare JM, Traverse JH, Henry TD, Dib N, Strumpf RK, Schulman SP, Gerstenblith G, DeMaria AN, Denktas AE, Gammon RS, Hermiller JB Jr, Reisman MA, Schaer GL, Sherman W. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (prochymal) after acute myocardial infarction. J Am Coll Cardiol. 2009 Dec 8;54(24):2277-86. doi: 10.1016/j.jacc.2009.06.055. — View Citation

Ishizawa K, Kubo H, Yamada M, Kobayashi S, Numasaki M, Ueda S, Suzuki T, Sasaki H. Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema. FEBS Lett. 2004 Jan 2;556(1-3):249-52. — View Citation

Iso Y, Spees JL, Serrano C, Bakondi B, Pochampally R, Song YH, Sobel BE, Delafontaine P, Prockop DJ. Multipotent human stromal cells improve cardiac function after myocardial infarction in mice without long-term engraftment. Biochem Biophys Res Commun. 2007 Mar 16;354(3):700-6. Epub 2007 Jan 17. — View Citation

Jiang Y, Jahagirdar BN, Reinhardt RL, Schwartz RE, Keene CD, Ortiz-Gonzalez XR, Reyes M, Lenvik T, Lund T, Blackstad M, Du J, Aldrich S, Lisberg A, Low WC, Largaespada DA, Verfaillie CM. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature. 2002 Jul 4;418(6893):41-9. Epub 2002 Jun 20. Erratum in: Nature. 2007 Jun 14;447(7146):879-80. — View Citation

King P. Pathogenesis of bronchiectasis. Paediatr Respir Rev. 2011 Jun;12(2):104-10. doi: 10.1016/j.prrv.2010.10.011. Epub 2010 Nov 24. — View Citation

Klyushnenkova E, Mosca JD, Zernetkina V, Majumdar MK, Beggs KJ, Simonetti DW, Deans RJ, McIntosh KR. T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci. 2005;12(1):47-57. — View Citation

Kotton DN, Fabian AJ, Mulligan RC. Failure of bone marrow to reconstitute lung epithelium. Am J Respir Cell Mol Biol. 2005 Oct;33(4):328-34. Epub 2005 Jun 16. — View Citation

Kotton DN, Ma BY, Cardoso WV, Sanderson EA, Summer RS, Williams MC, Fine A. Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development. 2001 Dec;128(24):5181-8. — View Citation

Krasnodembskaya A, Samarani G, Song Y, Zhuo H, Su X, Lee JW, Gupta N, Petrini M, Matthay MA. Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am J Physiol Lung Cell Mol Physiol. 2012 May 15;302(10):L1003-13. doi: 10.1152/ajplung.00180.2011. Epub 2012 Mar 16. — View Citation

Krasnodembskaya A, Song Y, Fang X, Gupta N, Serikov V, Lee JW, Matthay MA. Antibacterial effect of human mesenchymal stem cells is mediated in part from secretion of the antimicrobial peptide LL-37. Stem Cells. 2010 Dec;28(12):2229-38. doi: 10.1002/stem.544. — View Citation

Kumamoto M, Nishiwaki T, Matsuo N, Kimura H, Matsushima K. Minimally cultured bone marrow mesenchymal stem cells ameliorate fibrotic lung injury. Eur Respir J. 2009 Sep;34(3):740-8. doi: 10.1183/09031936.00128508. Epub 2009 Mar 26. — View Citation

Le Blanc K, Frassoni F, Ball L, Locatelli F, Roelofs H, Lewis I, Lanino E, Sundberg B, Bernardo ME, Remberger M, Dini G, Egeler RM, Bacigalupo A, Fibbe W, Ringdén O; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet. 2008 May 10;371(9624):1579-86. doi: 10.1016/S0140-6736(08)60690-X. — View Citation

Le Blanc K, Tammik C, Rosendahl K, Zetterberg E, Ringdén O. HLA expression and immunologic properties of differentiated and undifferentiated mesenchymal stem cells. Exp Hematol. 2003 Oct;31(10):890-6. — View Citation

Lee JW, Fang X, Gupta N, Serikov V, Matthay MA. Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16357-62. doi: 10.1073/pnas.0907996106. Epub 2009 Aug 31. — View Citation

Lee JW, Krasnodembskaya A, McKenna DH, Song Y, Abbott J, Matthay MA. Therapeutic effects of human mesenchymal stem cells in ex vivo human lungs injured with live bacteria. Am J Respir Crit Care Med. 2013 Apr 1;187(7):751-60. doi: 10.1164/rccm.201206-0990OC. — View Citation

Lee RH, Seo MJ, Reger RL, Spees JL, Pulin AA, Olson SD, Prockop DJ. Multipotent stromal cells from human marrow home to and promote repair of pancreatic islets and renal glomeruli in diabetic NOD/scid mice. Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17438-43. Epub 2006 Nov 6. — View Citation

Lee SH, Jang AS, Kim YE, Cha JY, Kim TH, Jung S, Park SK, Lee YK, Won JH, Kim YH, Park CS. Modulation of cytokine and nitric oxide by mesenchymal stem cell transfer in lung injury/fibrosis. Respir Res. 2010 Feb 8;11:16. doi: 10.1186/1465-9921-11-16. — View Citation

Lee SH, Lee EJ, Lee SY, Kim JH, Shim JJ, Shin C, In KH, Kang KH, Uhm CS, Kim HK, Yang KS, Park S, Kim HS, Kim YM, Yoo TJ. The effect of adipose stem cell therapy on pulmonary fibrosis induced by repetitive intratracheal bleomycin in mice. Exp Lung Res. 2014 Apr;40(3):117-25. doi: 10.3109/01902148.2014.881930. — View Citation

Liang J, Zhang H, Hua B, Wang H, Lu L, Shi S, Hou Y, Zeng X, Gilkeson GS, Sun L. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis. 2010 Aug;69(8):1423-9. doi: 10.1136/ard.2009.123463. Erratum in: Ann Rheum Dis. 2011 Jan;70(1):237. — View Citation

Ma N, Gai H, Mei J, Ding FB, Bao CR, Nguyen DM, Zhong H. Bone marrow mesenchymal stem cells can differentiate into type II alveolar epithelial cells in vitro. Cell Biol Int. 2011 Dec;35(12):1261-6. doi: 10.1042/CBI20110026. — View Citation

Mei SH, Haitsma JJ, Dos Santos CC, Deng Y, Lai PF, Slutsky AS, Liles WC, Stewart DJ. Mesenchymal stem cells reduce inflammation while enhancing bacterial clearance and improving survival in sepsis. Am J Respir Crit Care Med. 2010 Oct 15;182(8):1047-57. doi: 10.1164/rccm.201001-0010OC. Epub 2010 Jun 17. — View Citation

Miyahara Y, Nagaya N, Kataoka M, Yanagawa B, Tanaka K, Hao H, Ishino K, Ishida H, Shimizu T, Kangawa K, Sano S, Okano T, Kitamura S, Mori H. Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med. 2006 Apr;12(4):459-65. Epub 2006 Apr 2. — View Citation

Moodley Y, Atienza D, Manuelpillai U, Samuel CS, Tchongue J, Ilancheran S, Boyd R, Trounson A. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol. 2009 Jul;175(1):303-13. doi: 10.2353/ajpath.2009.080629. Epub 2009 Jun 4. — View Citation

Németh K, Leelahavanichkul A, Yuen PS, Mayer B, Parmelee A, Doi K, Robey PG, Leelahavanichkul K, Koller BH, Brown JM, Hu X, Jelinek I, Star RA, Mezey E. Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009 Jan;15(1):42-9. doi: 10.1038/nm.1905. Epub 2008 Nov 21. Erratum in: Nat Med. 2009 Apr;15(4):462. — View Citation

Ortiz LA, Dutreil M, Fattman C, Pandey AC, Torres G, Go K, Phinney DG. Interleukin 1 receptor antagonist mediates the antiinflammatory and antifibrotic effect of mesenchymal stem cells during lung injury. Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11002-7. Epub 2007 Jun 14. — View Citation

Ortiz LA, Gambelli F, McBride C, Gaupp D, Baddoo M, Kaminski N, Phinney DG. Mesenchymal stem cell engraftment in lung is enhanced in response to bleomycin exposure and ameliorates its fibrotic effects. Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8407-11. Epub 2003 Jun 18. — View Citation

Parekkadan B, van Poll D, Suganuma K, Carter EA, Berthiaume F, Tilles AW, Yarmush ML. Mesenchymal stem cell-derived molecules reverse fulminant hepatic failure. PLoS One. 2007 Sep 26;2(9):e941. — View Citation

Price AP, England KA, Matson AM, Blazar BR, Panoskaltsis-Mortari A. Development of a decellularized lung bioreactor system for bioengineering the lung: the matrix reloaded. Tissue Eng Part A. 2010 Aug;16(8):2581-91. doi: 10.1089/ten.TEA.2009.0659. — View Citation

Quittner AL, O'Donnell AE, Salathe MA, Lewis SA, Li X, Montgomery AB, O'Riordan TG, Barker AF. Quality of Life Questionnaire-Bronchiectasis: final psychometric analyses and determination of minimal important difference scores. Thorax. 2015 Jan;70(1):12-20. doi: 10.1136/thoraxjnl-2014-205918. Epub 2014 Oct 16. — View Citation

Rogers GB, Bruce KD, Martin ML, Burr LD, Serisier DJ. The effect of long-term macrolide treatment on respiratory microbiota composition in non-cystic fibrosis bronchiectasis: an analysis from the randomised, double-blind, placebo-controlled BLESS trial. Lancet Respir Med. 2014 Dec;2(12):988-96. doi: 10.1016/S2213-2600(14)70213-9. Epub 2014 Oct 14. Erratum in: Lancet Respir Med. 2015 Apr;3(4):e15. — View Citation

Rojas M, Xu J, Woods CR, Mora AL, Spears W, Roman J, Brigham KL. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Respir Cell Mol Biol. 2005 Aug;33(2):145-52. Epub 2005 May 12. — View Citation

Schuleri KH, Feigenbaum GS, Centola M, Weiss ES, Zimmet JM, Turney J, Kellner J, Zviman MM, Hatzistergos KE, Detrick B, Conte JV, McNiece I, Steenbergen C, Lardo AC, Hare JM. Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. Eur Heart J. 2009 Nov;30(22):2722-32. doi: 10.1093/eurheartj/ehp265. Epub 2009 Jul 8. — View Citation

Seitz AE, Olivier KN, Adjemian J, Holland SM, Prevots DR. Trends in bronchiectasis among medicare beneficiaries in the United States, 2000 to 2007. Chest. 2012 Aug;142(2):432-439. doi: 10.1378/chest.11-2209. — View Citation

Spees JL, Pociask DA, Sullivan DE, Whitney MJ, Lasky JA, Prockop DJ, Brody AR. Engraftment of bone marrow progenitor cells in a rat model of asbestos-induced pulmonary fibrosis. Am J Respir Crit Care Med. 2007 Aug 15;176(4):385-94. Epub 2007 May 11. — View Citation

Spees JL, Whitney MJ, Sullivan DE, Lasky JA, Laboy M, Ylostalo J, Prockop DJ. Bone marrow progenitor cells contribute to repair and remodeling of the lung and heart in a rat model of progressive pulmonary hypertension. FASEB J. 2008 Apr;22(4):1226-36. Epub 2007 Nov 21. — View Citation

Sueblinvong V, Loi R, Eisenhauer PL, Bernstein IM, Suratt BT, Spees JL, Weiss DJ. Derivation of lung epithelium from human cord blood-derived mesenchymal stem cells. Am J Respir Crit Care Med. 2008 Apr 1;177(7):701-11. Epub 2007 Dec 6. — View Citation

Sundin M, Orvell C, Rasmusson I, Sundberg B, Ringdén O, Le Blanc K. Mesenchymal stem cells are susceptible to human herpesviruses, but viral DNA cannot be detected in the healthy seropositive individual. Bone Marrow Transplant. 2006 Jun;37(11):1051-9. — View Citation

Tögel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol. 2005 Jul;289(1):F31-42. Epub 2005 Feb 15. — View Citation

Toonkel RL, Hare JM, Matthay MA, Glassberg MK. Mesenchymal stem cells and idiopathic pulmonary fibrosis. Potential for clinical testing. Am J Respir Crit Care Med. 2013 Jul 15;188(2):133-40. doi: 10.1164/rccm.201207-1204PP. Review. — View Citation

Tzouvelekis A, Paspaliaris V, Koliakos G, Ntolios P, Bouros E, Oikonomou A, Zissimopoulos A, Boussios N, Dardzinski B, Gritzalis D, Antoniadis A, Froudarakis M, Kolios G, Bouros D. 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. J Transl Med. 2013 Jul 15;11:171. doi: 10.1186/1479-5876-11-171. — View Citation

Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP. A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest. 2013 Jun;143(6):1590-1598. doi: 10.1378/chest.12-2094. — View Citation

Weiss DJ, Chambers D, Giangreco A, Keating A, Kotton D, Lelkes PI, Wagner DE, Prockop DJ; ATS Subcommittee on Stem Cells and Cell Therapies. An official American Thoracic Society workshop report: stem cells and cell therapies in lung biology and diseases. Ann Am Thorac Soc. 2015 Apr;12(4):S79-97. doi: 10.1513/AnnalsATS.201502-086ST. — View Citation

Weycker D, Edelsberg J, Oster G, Tino G. Prevalence and economic burden of bronchiectasis. Clin Pulm Med. 2005;12(4):205-9

Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, Cosgrove K, Vojnik R, Calfee CS, Lee JW, Rogers AJ, Levitt J, Wiener-Kronish J, Bajwa EK, Leavitt A, McKenna D, Thompson BT, Matthay MA. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015 Jan;3(1):24-32. doi: 10.1016/S2213-2600(14)70291-7. Epub 2014 Dec 17. — View Citation

Wong C, Jayaram L, Karalus N, Eaton T, Tong C, Hockey H, Milne D, Fergusson W, Tuffery C, Sexton P, Storey L, Ashton T. Azithromycin for prevention of exacerbations in non-cystic fibrosis bronchiectasis (EMBRACE): a randomised, double-blind, placebo-controlled trial. Lancet. 2012 Aug 18;380(9842):660-7. doi: 10.1016/S0140-6736(12)60953-2. — View Citation

Xu J, Mora A, Shim H, Stecenko A, Brigham KL, Rojas M. Role of the SDF-1/CXCR4 axis in the pathogenesis of lung injury and fibrosis. Am J Respir Cell Mol Biol. 2007 Sep;37(3):291-9. Epub 2007 Apr 26. — View Citation

Yamada M, Kubo H, Kobayashi S, Ishizawa K, Numasaki M, Ueda S, Suzuki T, Sasaki H. Bone marrow-derived progenitor cells are important for lung repair after lipopolysaccharide-induced lung injury. J Immunol. 2004 Jan 15;172(2):1266-72. Erratum in: J Immunol. 2004 Oct 1;173(7):4755. — View Citation

* Note: There are 63 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participant with treatment emergent serious adverse events	incidence of any treatment-emergent serious adverse events defined as the composite of death, non-fatal pulmonary embolism, stroke, hospitalization for worsening dyspnea and clinically significant laboratory test abnormalities	Week 4 post infusion
Secondary	Difference in Colony Forming Units (CFUs) in semiquantitative culture of sputum	Difference in CFUs in semiquantitative culture of sputum	Participants will be followed from 1 week to an expected average of 24 weeks following infusion.
Secondary	rate of decline of lung function	difference in absolute decline of forced expiratory volume at one second (FEV1) percent predicted	Participants will be followed from 12 weeks to an expected average of 24 weeks following infusion.
Secondary	frequency of acute exacerbations	increased cough and sputum production, fever, new or worsened dyspnea in less than 30 days, new or worsened hypoxemia in the absence of other identifiable causes	Participants will be followed from 12 weeks to an expected average of 48 weeks following infusion.
Secondary	reported dyspnea and quality of life assessment	using quality of life tool questionnaire QOL-B version 2	Participants will be followed from 4 weeks to an expected average of 48 weeks following infusion.
Secondary	death from any cause	death from any cause	Participants will be followed for the duration of the trial, which is an expected average of 48 weeks.