Figures
- FIGURE 1
Recent advances in the knowledge of different trajectories and aetiology (taxonomy) for COPD. Information from [1], [19] and [20].
- FIGURE 2
Different factors secreted (secretome) by mesenchymal stromal/stem cells (MSCs) and physiological processes that may act as potential targets for cell-based therapy. CAT: catalase; CCL: chemokine (C-C motif) ligand; CX3CL1: C-X3-C motif chemokine ligand 1; CXCL: chemokine (C-X-C motif) ligand; EGF: epidermal growth factor; FGF: fibroblast growth factor; FLT3: Fms related receptor tyrosine kinase 3; GM-CSF: granulocyte–macrophage colony-stimulating factor; Gpx: glutathione peroxidase; HGF: hepatocyte growth factor; IDO: indoleamine 2,3-dioxygenase; IGF-1: insulin-like growth factor 1; IL: interleukin; IP10: interferon-induced protein 10; KGF: keratinocyte growth factor; LAP: latency-associated peptide; NGF-3: nerve growth factor 3; PGE2: prostaglandin E2; PIGF: phosphatidylinositol glycan anchor biosynthesis class F; SOD: superoxide dismutase; TGF: transforming growth factor; TNF-α; tumour necrosis factor-α; VEGF: vascular endothelial growth factor.
- FIGURE 3
Outline of cell-based therapy methodologies for COPD treatment in nine published clinical trials. Studies by a) Ribeiro-Paes et al. [64] and Stessuk et al. [5], b) Weiss et al. [65], c) Stolk et al. [67], d) de Oliveira et al. [68], e) Armitage et al. [70], f) Le Thi Bich et al. [71], g) Hoang et al. [73] and h) Squassoni et al. [74]. 6MWT: 6-min walk test; AD-MSC: adipose tissue-derived mesenchymal stem cell; BM-MSC: bone marrow-derived mesenchymal stem cell; BMMC: bone marrow mononuclear cell; CBC: complete blood count; CSE: clinical simulation; CT: computed tomography; EBV: endobronchial valve; LVRS: lung volume reduction surgery; PFT: pulmonary function test; UC-MSC: umbilical cord-derived mesenchymal stem cell.
- FIGURE 4
Experimental design of the clinical protocol proposed by Squassoni et al. [74]. Reproduced from [74] with permission.
Tables
- TABLE 1
Studies that evaluated the use of stem cell therapies in COPD with published results
Registry code Enrolment (S/C) Patient conditions Intervention (cell source) Cell dosage Delivery route Main outcomes Ref. NCT01110252 4/4 Severe COPD Autologous BMMCs 1×108 cells·mL−1 Intravenous Autologous cell therapy for COPD patients is a safe procedure and free of adverse effects [5, 64] NCT00683722 62/46 Moderate-to-severe COPD Allogenic MSCs 1×108 cells per infusion (2×106 cells·min−1) Intravenous No infusion toxicities, deaths or adverse effects were observed
Systemic MSC administration appears to be safe[65] NCT01306513 10/7 Severe emphysema Autologous MSCs 1–2×106 cells·kg−1 Intravenous Procedure is safe and free of adverse effects [67] NCT04018729 10/10 Severe COPD Allogenic BM-MSCs 1×108 cells per 30 mL (2×107 cells·min−1) Intrabronchial No administration-related toxicities were observed, nor serious adverse effects or death [68] ACT12614000731695 9/9 Mild-to-very severe COPD Allogenic BM-MSCs 2×106 cells·kg−1 Intravenous MSC infusion showed no attributable adverse side-effects and was well tolerated [70] ISRCTN70443938 20/20 Moderate-to-severe COPD Allogenic UC-MSCs 1.5×106 cells·kg−1 Intravenous No infusion-related toxicities, death or severe adverse events were observed [71] NCT02412332 20/20 Moderate-to-severe COPD Autologous BMMCs and/or AD-MSCs 1×108 cells per infusion (single infusion); 5×107 cells per infusion (co-infusion) Intravenous Co-infusion of BMMCs and AD-MSCs is a safe procedure [74] NCT04433104 40/– – Allogenic UC-MSCs 1×106 cells·kg−1 Intravenous Study is not yet complete [73] The cell-based therapy methodologies for each clinical trial mentioned in this table are represented in figure 3. ACT: Australian Clinical Trial (australianclinicaltrials.gov.au); AD-MSC: adipose tissue-derived mesenchymal stem cell; BM-MSC: bone marrow-derived mesenchymal stem/stromal cell; BMMC: bone marrow mononuclear cell; ISRCTN: International Standard Registered Clinical Trial Number (isrctn.com); MSC: mesenchymal stem/stromal cell; NCT: National Clinical Trial (clinicaltrials.gov); S/C: started/completed; UC-MSC: umbilical cord-derived mesenchymal stem cell.
- TABLE 2
Clinical trials for COPD registered at clinicaltrials.gov (accessed 9 September 2022)
Registry code Enrolment (S/C) Follow-up Intervention (cell source) Delivery route Current status Phase NCT03044431 207/148 6 months Autologous PB-SCs and/or BM-MSCs Intravenous Completed NA NCT04047810 15/– 1 day Allogeneic MSCs Intravenous Ongoing (recruiting) I NCT02645305 20/– 12 months Autologous AD-MSCs Intravenous Unknown I/II NCT01110252 4/4 30 days Autologous BMMCs Intravenous Completed NA NCT02412332 20/20 12 months Autologous BMMCs and/or AD-MSCs Intravenous Unknown I/II NCT04433104 40/– 12 months Allogeneic UC-MSCs Intravenous Ongoing (recruiting) I/II NCT02216630 26/– 12 months Autologous AD-MSCs Intravenous Completed I/II NCT04206007 9/– 15 months Allogeneic UC-MSCs Intravenous Ongoing (recruiting) I NCT03228121 0/0 6 months Autologous MSCs Intravenous Withdrawn NA NCT05147688 20/– 48 months Allogeneic UC-MSCs Intravenous Ongoing (recruiting) I NCT03040674 489/241 6 months Autologous PB-SCs and/or BM-MSC Intravenous Completed NA NCT04018729 34/– 6 months BM-MSCs Endobronchial Unknown II/III NCT00683722 62/62 24 months Allogeneic MSCs (Prochymal) Intravenous Completed II NCT02161744 9/– 12 months Autologous AD-MSCs Intravenous Terminated (poor enrolment) I NCT03899298 5000/– 120 months Amniotic tissue-derived and UC-MSCs Intravenous plus nebuliser Ongoing (not yet recruiting) I NCT01916577 15/15 12 months Autologous BMMCs (mobilisation) Plerixafor applied subcutaneously Completed I NCT02041000 0/0 6 months Autologous AD-MSCs Intravenous Withdrawn NA NCT01953523 3000/– 120 months Autologous AD-MSCs Intravenous, intra-articular and soft tissue injection Completed NA NCT02348060 100/– 12 months Autologous AD-MSCs NM Unknown NM NCT01559051 0/0 6 months Autologous AD-MSCs Intravenous Withdrawn (company dissolved) I/II NCT03021681 18/– 24 months Autologous bronchial basal cells Bronchoscope transfusion Completed NA NCT04918706 30/– 48–60 months Allogeneic BM-MSCs Intravenous Ongoing (recruiting) II NCT01849159 0/0 24 months Allogeneic BM-MSCs Intravenous Withdrawn I/II NCT01758055 12/– 12 months Autologous BM-MSCs Endobronchial Unknown I NCT01306513 10/10 12 months Autologous BM-MSCs Intravenous Completed I AD-MSC: adipose tissue-derived mesenchymal stem cell; BM-MSC: bone marrow-derived mesenchymal stem cell; BMMC: bone marrow mononuclear cell; MSC: mesenchymal stem/stromal cell; NCT: National Clinical Trial (clinicaltrials.gov); NA: not applicable; NM: not mentioned; PB-SC: peripheral blood stem cell; S/C: started/completed; UC-MSC: umbilical cord-derived mesenchymal stem cell.
