Table 2.
Clinical studies on regenerative therapies in human lung disease.
| Indication/therapeutic area | Registration nr. and design | Treatment/dosing/timing | Outcome | References |
|---|---|---|---|---|
| LPS-induced human model of lung injury (n = 36) | ISRCTN 98813895 Randomized, double-blind, placebo-controlled trial |
KGF (palifermin) or placebo 60 μg/kg/day (i.v.) 3 days |
Increased Sp-D, increased alveolar IL-1Ra, MMP-9, GM-CSF (pro-repair/pro-resolving effect) | [30] |
| ARDS (n = 29) | ISRCTN95690673 Randomized, double-blind, placebo-controlled trial Phase 2 |
KGF (palifermin) or placebo 60 μg/kg (i.v.) 6 days |
No/worsening effect; fewer ventilator-free first 28 days; higher mortality at day 28 | [31] |
| AATD-emphysema (n = 262) | Randomized, double-blind, placebo-controlled trial Phase 2 |
RARγ-agonist (palovarotene-retinoid) 5 mg/day (oral) 12 months |
No effect | [52] |
| COPD-emphysema (n = 148) | Randomized, double-blind, placebo-controlled trial Phase 2 |
All-trans retinoic acid (ATRA), 13-cis retinoic acid (13-cRA:) or placebo ATRA: 1 mg/kg/d or 2 mg/kg/d (oral) 13-cRA: 1 mg/kg/d (oral) 6 months followed by a 3-month crossover period |
No effect | [53] |
| COPD (n = 6) | Randomized, double-blind, placebo-controlled trial Pilot trial |
FGF-2 2.5 ng by inhalation 3 times a day during two weeks |
Safe and well-tolerated No significant improvements in respiratory symptoms and lung function |
[54] |
| Mild/severe COVID-19 (n = 18) |
NCT04288102 Non-randomized, controlled trial Phase 1 |
UC-MSC 3 × 107 cells/infusion (i.v) Day: 0, 3, and 6 |
Safe and well-tolerated | [55] |
| Advanced COPD-emphysema (n = 4) |
NCT01110252 Single-arm trial Phase 1 |
Mononuclear cells (BMMC) 1x i.v. BMMS (autologous) |
Safe and well-tolerated | [56] |
| Moderate to severe COPD-emphysema (n = 62) |
NCT00683722 Randomized, double-blind, placebo-controlled trial Phase 2 |
BM-MSC 4x 100 × 106 cells/infusion (i.v.; allogeneic) Monthly |
Safe and well-tolerated, trend toward lower CRP | [57] |
| Severe COPD-emphysema (n = 8) |
NCT01306513 Single-arm trial Phase 1 |
BM-MSC 2x 1–2 × 106 BM-MSCs/kg (i.v.; autologous) 1 week apart |
Safe and well-tolerated; increase in alveolar septal CD31 | [58] |
| Severe COPD-emphysema (n = 10) |
NCT01872624 Randomized, patient-blinded, placebo-controlled trial Phase 1 |
BM-MSC 1x 108 cells (i.v.; allogeneic) Combined with EBV insertion |
Safe and well-tolerated, increased QoL, decreased CRP, decreased BODE and MMRC. | [59] |
| Mild-to-very severe stable COPD (n = 9) | ANZCTR12614000731695 Single-armed trial Phase I |
BM-MSC 2x 106 cells/kg (i.v.; allogeneic) 1 week apart 111indium-labeled MSC |
Safe and well-tolerated; Reduced MSC uptake in emphysema lungs, decreased systemic inflammation | [60] |
| COPD (n = 5) | Open-label, Single-armed trial Phase (1/2) |
UC-MSC 4x 1‒2x106BM-MSCs/kg (i.v.) |
Safe and well-tolerated; no significant effects | [61] |
| Moderate-to-severe COPD (n = 20) | ISRCTN70443938 Placebo-controlled trial Phase 1/2 |
UC-MSC 1x 106 cells/kg (i.v.) |
Safe and well-tolerated; decreased MMRC and CAT score, lower number of exacerbations | [62] |
| Moderately severe IPF (n = 8) |
NCT01385644 Single-arm Phase 1b |
PL-MSC 2.5 × 106 cells/mL (i.v.) |
Safe and well-tolerated | [63] |
| Moderate and progressive IPF (n = 16) | Single-arm Phase 1 |
Alveolar type II cells 4x 1‒1.2 × 109 cells bronchoscopic instillation 15 days apart |
Safe and well-tolerated | [64] |
| Non-CF bronchiectasis (n = 2) |
NCT02722642 Single-arm Pilot |
SOX9+ basal cells 106/kg body weight bronchoscopic instillation |
Recruitment ongoing (n = 20 estimated) | [65] |
BMMC: bone marrow mononuclear cell; BM-MSC: bone marrow‒derived MSC; PL-MSC: placenta-derived MSC; RARγ: γ-type retinoic acid receptor; UC-MSC: umbilical cord‒derived MSC.