Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial

Chest

Volumn 151, Issue 5, 2017, Pages 971-981

  Glassberg, Marilyn K ^a   Minkiewicz, Julia ^a   Toonkel, Rebecca L ^b   Simonet, Emmanuelle S ^a   Rubio, Gustavo A ^a   DiFede, Darcy ^a   Shafazand, Shirin ^a   Khan, Aisha ^a   Pujol, Marietsy V ^a   LaRussa, Vincent F ^c   Lancaster, Lisa H ^d   Rosen, Glenn D ^e   Fishman, Joel ^a   Mageto, Yolanda N ^f   Mendizabal, Adam ^g   Hare, Joshua M ^a  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b FLORIDA INTERNATIONAL UNIVERSITY   (United States)

^c University of Louisville School of Medicine   (United States)

^d VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^e BRISTOL MYERS SQUIBB   (United States)

^f UNIVERSITY OF VERMONT COLLEGE OF MEDICINE   (United States)

^g EMMES CORPORATION   (United States)

Author keywords

bone marrow; idiopathic pulmonary fibrosis; mesenchymal stem cells; safety trial

Indexed keywords

CARBON MONOXIDE;

AGED; ALLOTRANSPLANTATION; CLINICAL TRIAL; DISEASE COURSE; DYSPNEA; FEMALE; HOSPITALIZATION; HUMAN; IDIOPATHIC PULMONARY FIBROSIS; INTRAVENOUS DRUG ADMINISTRATION; LUNG DIFFUSION CAPACITY; MALE; MESENCHYMAL STEM CELL TRANSPLANTATION; MIDDLE AGED; MORTALITY; PATHOPHYSIOLOGY; PHASE 1 CLINICAL TRIAL; PROCEDURES; PULMONARY EMBOLISM; STROKE; TOTAL LUNG CAPACITY; VITAL CAPACITY; WALK TEST;

ADMINISTRATION, INTRAVENOUS; AGED; CARBON MONOXIDE; DISEASE PROGRESSION; DYSPNEA; FEMALE; HOSPITALIZATION; HUMANS; IDIOPATHIC PULMONARY FIBROSIS; MALE; MESENCHYMAL STEM CELL TRANSPLANTATION; MIDDLE AGED; MORTALITY; PULMONARY DIFFUSING CAPACITY; PULMONARY EMBOLISM; STROKE; TOTAL LUNG CAPACITY; TRANSPLANTATION, HOMOLOGOUS; VITAL CAPACITY; WALK TEST;

EID: 85019145876     PISSN: 00123692     EISSN: 19313543     Source Type: Journal    
DOI: 10.1016/j.chest.2016.10.061     Document Type: Conference Paper

References (32)

1. 1 Raghu G, Collard HR, Egan JJ, et al. An official ATS/ERS/JRS/ALAT statement: idiopathic pulmonary fibrosis: evidence-based guidelines for diagnosis and management. Am J Resp Crit Care Med.183(6):788-824.
2. 2 Travis, W.D., Hunninghake, G., King, T.E. Jr., et al. Idiopathic nonspecific interstitial pneumonia: report of an American Thoracic Society project. Am J Resp Crit Care Med 177:12 (2008), 1338–1347.
3. 3 Nishimura, K., Kitaichi, M., Izumi, T., Nagai, S., Kanaoka, M., Itoh, H., Usual interstitial pneumonia: histologic correlation with high-resolution CT. Radiology 182:2 (1992), 337–342.
4. 4 Johkoh, T., Muller, N.L., Cartier, Y., et al. Idiopathic interstitial pneumonias: diagnostic accuracy of thin-section CT in 129 patients. Radiology 211:2 (1999), 555–560.
5. 5 King, T.E. Jr., Bradford, W.Z., Castro-Bernardini, S., et al. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med 370:22 (2014), 2083–2092.
6. 6 Richeldi, L., Cottin, V., du Bois, R.M., et al. Nintedanib in patients with idiopathic pulmonary fibrosis: Combined evidence from the TOMORROW and INPULSIS((R)) trials. Res Med 113 (2016), 74–79.
7. 7 Moodley, Y., Atienza, D., Manuelpillai, U., et al. Human umbilical cord mesenchymal stem cells reduce fibrosis of bleomycin-induced lung injury. Am J Pathol 175:1 (2009), 303–313.
8. 8 Rojas, M., Xu, J., Woods, C.R., et al. Bone marrow-derived mesenchymal stem cells in repair of the injured lung. Am J Resp Cell Mol Bio 33:2 (2005), 145–152.
9. 9 Tashiro, J., Elliot, S.J., Gerth, D.J., et al. Therapeutic benefits of young, but not old, adipose-derived mesenchymal stem cells in a chronic mouse model of bleomycin-induced pulmonary fibrosis. Transl Res 166:6 (2015), 554–567.
10. 10 Ortiz, L.A., Gambelli, F., McBride, C., et al. 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 100:14 (2003), 8407–8411.
11. 11 Ishizawa, K., Kubo, H., Yamada, M., et al. Bone marrow-derived cells contribute to lung regeneration after elastase-induced pulmonary emphysema. FEBS Lett 556:1-3 (2004), 249–252.
12. 12 Spees, J.L., Pociask, D.A., Sullivan, D.E., et al. Engraftment of bone marrow progenitor cells in a rat model of asbestos-induced pulmonary fibrosis. Am J Resp Crit Care Med 176:4 (2007), 385–394.
13. 13 Spees, J.L., Whitney, M.J., Sullivan, D.E., et al. Bone marrow progenitor cells contribute to repair and remodeling of the lung and heart in a rat model of progressive pulmonary hypertension. FASEB J 22:4 (2008), 1226–1236.
14. 14 Bonfield, T.L., Koloze, M., Lennon, D.P., Zuchowski, B., Yang, S.E., Caplan, A.I., Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model. Am J Physiol 299:6 (2010), L760–L770.
15. 15 Lee, J.W., Fang, X., Gupta, N., Serikov, V., Matthay, M.A., 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 106:38 (2009), 16357–16362.
16. 16 Hare, J.M., Traverse, J.H., Henry, T.D., et al. 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 54:24 (2009), 2277–2286.
17. 17 Liang, J., Zhang, H., Hua, B., et al. Allogenic mesenchymal stem cells transplantation in refractory systemic lupus erythematosus: a pilot clinical study. Ann Rheum Dis 69:8 (2010), 1423–1429.
18. 18 Hare, J.M., Fishman, J.E., Gerstenblith, G., et al. 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 308:22 (2012), 2369–2379.
19. 19 Chambers, D.C., Enever, D., Ilic, N., et al. A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis. Respirology 19:7 (2014), 1013–1018.
20. 20 Le Blanc, K., Frassoni, F., Ball, L., et al. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 371:9624 (2008), 1579–1586.
21. 21 Tzouvelekis, A., Paspaliaris, V., Koliakos, G., et al. 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, 11, 2013, 171.
22. 22 Weiss, D.J., Casaburi, R., Flannery, R., LeRoux-Williams, M., Tashkin, D.P., A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest 143:6 (2013), 1590–1598.
23. 23 Wilson, J.G., Liu, K.D., Zhuo, H., et al. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet 3:1 (2015), 24–32.
24. 24 Heldman, A.W., DiFede, D.L., Fishman, J.E., et al. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA 311:1 (2014), 62–73.
25. 25 Golpanian, S., DiFede, D.L., Pujol, M.V., et al. Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: a phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty. Oncotarget 7:11 (2016), 11899–11912.
26. 26 Trachtenberg, B., Velazquez, D.L., Williams, A.R., et al. Rationale and design of the Transendocardial Injection of Autologous Human Cells (bone marrow or mesenchymal) in Chronic Ischemic Left Ventricular Dysfunction and Heart Failure Secondary to Myocardial Infarction (TAC-HFT) trial: a randomized, double-blind, placebo-controlled study of safety and efficacy. Am Heart J 161:3 (2011), 487–493.
27. 27 Ley, B., Bradford, W.Z., Weycker, D., Vittinghoff, E., du Bois, R.M., Collard, H.R., Unified baseline and longitudinal mortality prediction in idiopathic pulmonary fibrosis. Eur Resp J 45:5 (2015), 1374–1381.
28. 28 Lama, V.N., Phan, S.H., The extrapulmonary origin of fibroblasts: stem/progenitor cells and beyond. Proc Am Thorac Soc 3:4 (2006), 373–376.
29. 29 Phillips, R.J., Burdick, M.D., Hong, K., et al. Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis. J Clin Invest 114:3 (2004), 438–446.
30. 30 Salazar, K.D., Lankford, S.M., Brody, A.R., Mesenchymal stem cells produce Wnt isoforms and TGF-beta1 that mediate proliferation and procollagen expression by lung fibroblasts. Am J Physiol 297:5 (2009), L1002–L1011.
31. 31 Hashimoto, N., Jin, H., Liu, T., Chensue, S.W., Phan, S.H., Bone marrow-derived progenitor cells in pulmonary fibrosis. J Clin Invest 113:2 (2004), 243–252.
32. 32 Raghu, G., Collard, H.R., Anstrom, K.J., et al. Idiopathic pulmonary fibrosis: clinically meaningful primary endpoints in phase 3 clinical trials. Am J Resp Crit Care Med 185:10 (2012), 1044–1048.