TABLE 1

Some recent preclinical and clinical studies of lung diseases using mesenchymal stem/stromal cells (MSCs)

IndicationStudyCell sourceDoseApplication routeStudy designResultReference
COPDPreclinicalHuman MSCs, bone marrow-derived0.1, 5, 25 or 125×103 MSCs·g-1i.v.Elastase-induced emphysema in miceReduced fibrosis, reduced inflammation[10]
COPDPreclinicalHuman MSCs, cord blood-derived5×104 MSCs per mousei.v.Cigarette smoke-induced COPD in miceReduced inflammation, increased regeneration[11]
COPDPreclinicalRat MSCs6×106 MSCs per rati.t.Cigarette smoke-induced COPD in ratsReduced inflammation, improved lung function[12]
COPDPreclinicalRat MSCs, bone marrow-derived6×106 MSCs per rati.t.Cigarette smoke-induced COPD in ratsReduced inflammation[13]
COPDPreclinicalHuman MSCs, bone marrow or iPSC-derived3×106 bone marrow-derived MSCs or iPSC-derived MSCs per mousei.v.Cigarette smoke-induced COPD in miceReduced inflammation[14]
COPDClinicalAllogeneic human MSCs, bone marrow-derived, non-HLA-matched4-monthly infusions of 100×106 MSCs per patienti.v.Phase 2, prospective, randomised, double-blind, placebo (vehicle)-controlled (n=62)MSC treatment was safe, no improvement of lung function, reduced levels of CRP[15]
EmphysemaClinicalAllogeneic human MSCs, bone marrow-derived1×108 MSCs per patientBr.Phase 1, prospective, patient-blinded, randomised, placebo-controlled (n=10)MSC treatment was safe, reduced systemic inflammation[16]
ALI/ARDSPreclinicalHuman MSCs, umbilical cord- and bone marrow-derived1×107 human MSCs·kg-1i.v.Escherichia coli-induced ALI in ratsProlonged animal survival, reduced inflammation[17]
ALI/ARDSPreclinicalSyngeneic murine MSCs2.5×105 MSCs per mousei.v.LPS-induced ALI in miceReduced inflammation, reduced lung permeability[18]
ALI/ARDSPreclinicalSyngeneic murine MSCs5×105 MSCs per mousei.v.Bleomycin-induced ALI in miceProlonged animal survival, reduced inflammation[19]
ALI/ARDSPreclinicalHuman MSCs5×105 MSCs per mousei.t.LPS-induced ALI in miceProlonged animal survival, reduced pulmonary oedema[20]
ALI/ARDSPreclinicalRat MSCs, bone marrow-derived5×106 MSCs per rati.v.LPS-induced ALI in ratsReduced inflammation, reduced lung permeability[21]
ALI/ARDSPreclinicalRat MSCs, bone marrow-derived5×106 MSCs per rati.v.LPS-induced ALI in ratsReduced inflammation, reduced lung injury[22]
ALI/ARDSPreclinicalHuman MSCs, menstrual blood-derived1×106 cells per mousei.v.LPS-induced ALI in miceReduced inflammation, reduced lung permeability, reduced lung injury[23]
ALI/ARDSClinicalAllogeneic human MSCs, bone marrow-derived1×106, 5×106 or 10×106 MSCs·kg-1i.v.Phase 1, multicentre, open-label, dose-escalation study (n=9)MSC treatment was safe
Improvement of mean lung injury score and SOFA score
Decrease in levels of IL-6 and IL-8
[24]
ALI/ARDSClinicalAllogeneic human MSCs, adipose tissue-derived1×106 MSCs·kg-1i.v.Phase 1, randomised, placebo-controlled pilot study (n=12)MSC treatment was safe[25]
IPFPreclinicalAllogeneic murine MSCs, bone marrow-derived5×104 MSCs·g-1i.v.Bleomycin-induced fibrosis in miceReduced fibrosis[26]
IPFPreclinicalAllogeneic murine MSCs, bone marrow-derived5×105 MSCs per mousei.v.Bleomycin-induced fibrosis in miceReduced inflammation[27]
IPFPreclinicalHuman MSCs, Wharton's jelly-derived1×106 MSCs per mousei.v.Bleomycin-induced fibrosis in miceReduced inflammation[28]
IPFPreclinicalHuman MSCs, adipose-derived40×106 MSCs·kg-1i.v.Bleomycin-induced fibrosis in miceReduced fibrosis[29]
IPFPreclinicalSyngeneic MSCs, bone marrow-derived5×105 MSCs per mousei.t.Bleomycin-induced fibrosis in miceImproved pulmonary respiratory functions, reduced fibrosis[30]
IPFPreclinicalAutologous rat MSCs, bone marrow-derived2×106 MSCs per rati.v.Silica instillation-induced fibrosis in ratsReduced fibrosis[31]
IPFClinicalAllogeneic human MSCs, placenta-derived1×106 or 2×106 MSCs·kg-1i.v.Phase 1b, single-centre, nonrandomised, dose escalation study (n=8)MSC treatment was safe
No evidence of worsening fibrosis
[32]
IPFClinicalAutologous adipose tissue-derived MSCs5×105 MSC·kg-1i.v.Phase 1b, prospective, nonrandomised, not placebo-controlled (n=14)MSC treatment was safe[33]

COPD: chronic obstructive pulmonary disease; ALI: acute lung injury; ARDS: acute respiratory distress syndrome; IPF: idiopathic pulmonary fibrosis; i.t.: intratracheal; iPSC: induced pluripotent stem cells; HLA: human leukocyte antigen; CRP: C-reactive protein; Br.: bronchoscopy; LPS: lipopolysaccharide; SOFA: sequential organ failure assessment; IL: interleukin.