Marilyn Glassberg, MD
Professor of Medicine and Surgery
Miller School of Medicine, University of Miami
Miami, Florida

Chambers DC, Enever D, Ilic N, et al. A phase 1b study of placenta-derived mesenchymal stromal cells in patients with idiopathic pulmonary fibrosis. Respirology. 2014;19(7):1013-1018.

IPF is characterized by impaired pulmonary function associated with pulmonary scarring. This process has been attributed to failed tissue repair following epithelial injury.1,2 Mesenchymal stromal cells (MSC) are present in all vascularized tissues and organs and can differentiate into multiple tissues.3,4 These multipotent cells can be obtained from a variety of tissues such as placenta, umbilical cord, bone marrow, and adipose. The present study by Chambers et al examines the safety of infused placenta-derived MSC in patients with IPF.

Study Design

  • Phase 1b, open-label, single center, nonrandomized, dose-escalation study
  • 8 patients with moderate to severe IPF
    • ATS/ERS criteria5
    • Honeycombing > 5% in ≤ 3 of 6 lung zones
    • FVC ≥ 50% pred
    • DLCO ≥ 25% pred
  • Primary endpoint: Safety
  • Secondary endpoints
    • Changes in lung function (FVC and DLCO)
    • 6-min walk distance (6MWD)
    • Gas exchange (resting PaO2) at 1, 3, and 6 months post-MSC infusion
    • Lung fibrosis score (HRCT) at 3 and 6 months compared with baseline
  • MSC derived from two placentas
  • Dosing: 1 × 106 MSC/kg escalated to 2 × 106 MSC/kg
  • Infused via a large peripheral arm vein


Several minor and transient adverse events attributable to the MSC infusion occurred during the first 4 hours. One patient developed a small bowel obstruction and new lingular and left lower lobe consolidation 5 days after receiving 1 × 106 MSC/kg. The pulmonary consolidation resolved with antibiotic treatment but was thought to be possibly related to the MSC infusion. Three episodes of bronchitis/chest infection in one subject at 4, 6 and 15 weeks post-infusion were possibly related to MSC treatment but resolved with antibiotic therapy. One patient in the low dose group experienced an IPF exacerbation 176 days after infusion that resolved with prednisolone and was felt to be unrelated to MSC treatment. One patient in the high dose group experienced disease progression with worsening lung function and oxygenation at 6 months, possibly related to MSC treatment. There were no clinically significant changes in any of the peripheral blood safety parameters.

Patients’ median FVC fell transiently at 1 and 3 months, but returned to baseline. The DLCO and 6MWD remained stable at 1, 3 and 6 months. Neither the lung fibrosis score nor resting PaO2 changed significantly during the study. The authors conclude that this small study showed no evidence of increased safety risk associated with MSC infusion beyond normal IPF disease progression.

Expert Opinion
Multipotent cells from a variety of tissues such as placenta, umbilical cord, adipose, and other tissues are being actively investigated in other diseases and recent studies in IPF suggest that this study is similar to one reported by Tzouvelekis et al with endobronchial administration of adipose-derived stromal cells-stromal vascular fraction.6 Taken together, these studies suggest that the use of MSCs in patients with IPF is safe, carefully designed clinical trials of MSCs are warranted.7,8 Other clinical trials are recruiting patients and will expand these findings (http://www.clinicaltrials.gov).
There are several open issues in this area, including

  • Best source of MSC (placental tissue, adipose tissue, or bone marrow)
  • Safety and efficacy of autologous vs allogeneic cells
  • Optimal in vitro cell processing
  • Best route of administration (IV, endobronchial, other?)
  • Optimal dosing (cell number, frequency and number of doses)
  • Monitoring patients and criteria for success of clinical trials
  • Patient selection
  • Interaction with pirfenidone or nintedanib and staging of treatments

In summary, MSCs for IPF appear to have a good safety profile. Larger multicenter trials addressing safety and efficacy may be warranted in the near future.


1. Faner R, Rojas M, Macnee W, Agusti A. Abnormal lung aging in chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2012;186:306–313.

2. Sisson TH, Mendez M, Choi K, et al. Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis. Am J Respir Crit Care Med. 2010;181:254–263.

3. Antunes MA, Laffey JG, Pelosi P, Rocco PR. Mesenchymal stem cell trials for pulmonary diseases. J Cell Biochem. 2014;115(6):1023-1032.

4. Glenn JD, Whartenby KA. Mesenchymal stem cells: Emerging mechanisms of immunomodulation and therapy. World J Stem Cells. 2014;6(5):526-539.

5. 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 Respir Crit Care Med. 2011;183:788–824.

6. 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. 2013;11:171.

7. 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;188(2):133-140.

8. Glassberg MK, Toonkel RL. Moving stem cell therapy to patients with idiopathic pulmonary fibrosis. Respirology. 2014;19(7):950-951.