Table 1.
The current state of the field for lung stem cell therapies
| Lung disease | Approach for stem cell‐based therapy | Current stage of development | Challenges/Next steps |
|---|---|---|---|
| CF | • Gene corrected autologous iPSC, differentiated to lung airway progenitor cells for transplant to lung | • Research |
• Differentiation to appropriate cell type • “Making space” in the niche for engraftment • Engraftment efficiency and durability |
| hPAP | • Gene corrected autologous HSC, differentiated to macrophages for transplant to lung | • Preclinical development |
• Translation of gene correction from mouse to human HSC • Using the best gene correction technology • IND for the gene corrected cell product |
| BPD |
• Cord‐blood derived MSC delivered to lung airway • MSC (source of MSC not specified) |
• NCT02381366 Phase I–II U.S. • NCT01828957 Phase II Korea • NCT02443961 Phase I Spain |
• Safety of MSC treatment in pre‐term infants • Efficacy in placebo controlled trials • Understanding mechanism of action |
| ARDS |
• Allogeneic bone marrow derived MSC administered intravenously • Allogeneic MSC administered intravenously |
• NCT02097641 Phase II U.S. • NCT02804945 Phase II U.S. |
• Optimal source of MSCs • Evidence for efficacy • Understanding mechanism of action |
| IPF |
• Allogeneic bone marrow‐derived MSC administered intravenously • Placental MSC administered intravenously • Autologous bone‐marrow derived MSC administered endobronchially |
• NCT02013700 Phase I U.S. • NCT01385644 Phase I Australia • NCT01919827 Phase I Spain |
• Safety of MSC treatment in IPF patients • Better understanding of disease etiology • Understanding mechanism of action • Efficacy in placebo controlled trials |
| PAH |
• eNOS‐transfected autologous endothelial progenitor cells delivered to the pulmonary artery • Allogeneic cardiosphere derived cells (CDC) administered via central intravenous delivery |
• NCT00469027 Phase I Canada • NCT03001414 Phase II Canada • NCT03145298 Phase Ia/b U.S. |
• Patient recruitment • Manufacturing costs (eNOS‐EPC) • Understanding mechanism of action • Safety in PAH patients (CDC) • Efficacy in placebo controlled trials |
Abbreviations: ARDS, acute respiratory distress syndrome; BPD, bronchopulmonary dysplasia; CF, cystic fibrosis; eNOS, endothelial nitric oxide synthase; hPAP, hereditary pulmonary alveolar proteinosis; HSC, hematopoietic stem cells; IPF, idiopathic pulmonary fibrosis; iPSC, induced pluripotent stem cells; MSC, mesenchymal stem cells; PAH, pulmonary arterial hypertension.