Table 2.
Clinical trials used MSCs to treat neonatal diseases.
| References/year/study location | ClinicalTrials.gov identifier | Study design | Disease/pathology | Age group | No. of patient | Cell source | Route of administration | Dose | Frequency of cell administration | Follow up period | Safety outcome | Key efficacy outcome | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C | T | ||||||||||||
| Chang et al. (11), 2014, South Korea | NCT01297205 | Phase 1 dose-escalation clinical trial | BPD | 5 to 14-day old (23–29 gestational weeks) | 0 | 9 | Allogeneic UCB-MSCs (Pneumostem®) | Intratracheal | Group A: 3 patients received 1 × 107 cells/kg Group B: 6 patients received 2 × 107 cells/kg |
Single dose | 84 days | - No MSC related AE - No dose-limiting toxicities - No tumor formation |
- BPD severity reduced - Retinopathy of prematurity demanding surgery occurred less in the MSC-treated group compared to the historical corresponding control group - Significant declined in IL-6, IL-8, MMP-9, TNF-a, and TGF-b1 levels in tracheal aspirates at day 7 |
| Ahn al. (16), 2014, South Korea | NCT01632475 | Phase I trial | BPD | 5 to 14-day old (23–29 gestational weeks) | 0 | 9 | Allogeneic UCB-MSCs (Pneumostem®) | Intratracheal | Group A: 3 patients received 1 × 107 cells/kg Group B: 6 patients received 2 × 107 cells/kg |
Single dose | 24 months | - No MSC-related AE | - Infants treated with MSCs did not require supplemental oxygen upon discharge compared to 22% in the historical corresponding control group - Infants treated with MSCs did not develop asthma and did not need persistent steroid/bronchodilator therapy as long as 24 months of CA - MSC treatment minimized risk of neurodevelopmental morbidities. |
| Álvarez-Fuente et al. (17), 2018, Spain | – | Phase 1 trial | BPD | Patient1: 5-month old Patient 2: 85-day old |
0 | 2 | Allogeneic BMSCs | Intravenous | Patient1: Increasing weekly dose: 1.1 × 106 cells/kg up to 13.9 × 106 cells/kg Patient 2: 5 × 106 cells/kg per week for 3 consecutive weeks |
Patient 2 received 3 doses | – | - No MSC-related AE | - Inflammatory and lung injury biomarkers decreased - MSCs failed to reverse late stage of lung fibrosis, thus patients did not survive |
| Lin et al. (18), 2018, Taiwan | – | Case study | BPD with ARDS | 10-month old | 0 | 1 | Allogeneic BMSCs | Intratracheal | 6.25 × 106 cells/kg | Single dose | - | - No MSC-related AE | - Improvement in respiratory functions - ECMO support was detached at 25 days after transfusion - Improvement in lung fibrosis |
| Powell and Silvestri (19), 2019, USA | NCT02381366 | Phase 1, open-label, dose-escalation trial | BPD | 6 to 14-day old | 0 | 12 | Allogeneic UCB-MSCs (Pneumostem®) | Intratracheal | Group A: 6 patients received 1 × 107 cells/kg Group B: 6 patients received 2 × 107 cells/kg |
Single dose | Up to 20 months CA | - No severe AEs related to MSCs - No dose-limiting toxicities. |
- All patients developed BPD - 10/12 patients developed severe BPD showed improvement at day 84 after transfusion - Potential effectiveness could not be established. |
| Ahn et al. (12), 2018, South Korea | NCT02274428 | Phase I dose-escalation clinical trial | IVH (Grade 4) | 11.6 ± 0.9-day old | 0 | 9 | Allogeneic UCB-MSCs | Intraventricular | Group A: 3 patients received 5 × 106 cells/kg Group B: 6 patients received 1 × 107 cells/kg |
Single dose | NA | - No fatality - No anaphylactic reaction - Severe AEs observed were not related to MSC transplantation |
– |
| Akduman et al. (13), 2019, Turkey | – | Case study | NEC (SVT related) | 22-day old | 0 | 1 | Allogeneic UC-MSCs | Intravenous | 1 × 107 cells/transfusion | Single dose | 12 months | - No AE | - Intestinal blood supply improved - Saved the remaining of the necrotic intestine after laparotomy - Helped maintain the baby growth and neurodevelopment on par with babies of his age. |
AE, adverse event; ARDS, acute respiratory distress syndrome; BMSCs, bone marrow derived mesenchymal stromal cells; BPD, bronchopulmonary dysplasia; CA, corrected age; C- control; T, treatment; UC-MSCs, umbilical cord derived mesenchymal stromal cells; UCB-MSCs, umbilical cord blood derived mesenchymal stromal cells; IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis; SVT, supraventricular tachycardia.