Table 1.
Summary of clinical trials in KD using MSC registered at ClinicalTrials.Gov. Search done on 23rd April 2021.
| NCT number | Status | Phases | Start date | Cell source | Donor source | Dose frequency (N) | Infusion route | Results | References |
|---|---|---|---|---|---|---|---|---|---|
| Acute Kidney Injury | |||||||||
| NCT00733876 | Completed | Phase 1 | 2008 | BM-MSC | Allogeneic | 2 × 106 cells/kg body mass N = 1 |
Ia | No AE or SAE ↓40% hospitalization stay and readmission CKD was stable up to 16 mo follow-up No hemodialysis required |
(14–17) |
| NCT01602328 | Completed | Phase 2 | 2012 | BM-MSCa | Allogeneic | 2 × 106 cells/kg body mass N = 1 |
Iv | ~Recovery, need for dialysis, 30-day mortality, AE and SAE between treated and control groups | (18) |
| NCT01275612 | Withdrawn | Phase 1 | 2010 | BM-MSC | Autologous | 1 × 10∧6 cells/kg N = 1 |
Iv | Patients evaluated not meet the primary criterion | (19) |
| NCT04194671 | Not yet recruiting | Phase 1|Phase 2 | 2020 | UC-MSC | Allogeneic | NA N = 2, 7 d apart |
Iv | ||
| NCT03015623 | Active, not recruiting | Phase 1|Phase 2 | 2017 | BM-MSC2 | Allogeneic | SBI-101 + 2.5 × 108 vs. 7.5 × 108 | Time of hemodialysis | ||
| NCT04445220 | Recruiting | Phase 1|Phase 2 | 2020 | BM-MSCb | Allogeneic | SBI-101 + 2.5 × 108 vs. 7.5 × 108 | Time of hemodialysis | ||
| Sepsis-Induced AKI | |||||||||
| NCT02421484 | Completed | Phase 1 | 2015 | BM-MSC | Allogeneic | 0.3 vs. 1 vs. 3 × 106 cells/kg body mass N = 1 |
Iv | No AE or SAE ~Efficacy between treated and control groups |
(20) |
| NCT03369275 | Not yet recruiting | Phase 2 | 2018 | BM-MSC | Allogeneic | 3 × 106 cells/kg body mass N = 1 |
Iv | ||
| Chronic and End-Stage Kidney Disease | |||||||||
| NCT02966717 | Active, not recruiting | Phase 2 | 2016 | BM-MSC | Allogeneic | 1 × 106 cells/kg body mass N = 2, 2 weeks apart |
iv | ||
| NCT02166489 | Completed | Phase 1 | 2014 | BM-MSC | Autologous | 2 × 106 cells/kg body mass N = 1 |
iv | No AE or SAE ~ Renal function |
(21) |
| NCT02195323 | Completed | Phase 1 | 2014 | BM-MSC | Autologous | 2 × 106 cells/kg body mass N = 1 |
iv | ||
| NCT03321942 | Unknown status | Phase 1 | 2017 | AT-MSC | Autologous | NA | iv | ||
| NCT03939741 | Recruiting | Phase 1|Phase 2 | 2019 | SVF | Autologous | 1 × 106 in 5 mL N = 1 |
iv | ||
| Focal Segmental Glomerulosclerosis | |||||||||
| NCT02382874 | Completed | Phase 1 | 2015 | BM-MSC | Autologous | 2 × 106 cells/kg body mass N = 1 |
iv | ||
| Atherosclerotic Renovascular Disease | |||||||||
| NCT04392206 | Recruiting | Phase 1 | 2020 | AT-MSC | Allogeneic | 3 vs. 5 × 106 cells/kg body mass N = 1 |
Time of hemodialysis | ||
| NCT01840540 | Completed | Phase 1 | 2013 | AT-MSC | Autologous | 1 × 105 vs. 2.5 × 105 cells/kg body mass N = 1 |
ia | ↑ Cortical perfusion ↑ Renal blood flow ↓ Tissue hypoxia ↑ GFR 3 mo follow-up |
(22) |
| NCT02266394 | Completed | Phase 1 | 2014 | AT-MSC | Autologous | NA | ia | ||
| Diabetic Nephropathy | |||||||||
| NCT01843387 | Completed | Phase 1|Phase 2 | 2013 | BM-MSCc | Allogeneic | 1.5 vs. 3 108 cells N = 1 |
iv | Trend to stabilized or improved eGFR | (23) |
| NCT03288571 | Not yet recruiting | Phase 1|Phase 2 | 2019 | UC-MSC | Allogeneic | NA N = 3, 2 w apart in each kidney |
intra-renal | ||
| NCT04216849 | Recruiting | Phase 1|Phase 2 | 2020 | UC-MSC | Allogeneic | 1.5 × 106 cells/kg body mass N = 5, course of 32 w |
iv | ||
| NCT04562025 | Recruiting | Phase 1 | 2020 | UC-MSC | Allogeneic | 1 × 106 cells/kg body mass N = 3, weekly |
iv | ||
| NCT02585622 | Recruiting | Phase 1|Phase 2 | 2017 | BM-MSCd | Allogeneic | 0.8 vs. 1.6 vs. 2.4 × 108 cells N = 1 |
iv | ||
| NCT04125329 | Recruiting | Phase 1 | 2020 | UC-MSC | Allogeneic | 1 × 106 cells/kg body mass N = 3, monthly |
iv | ||
| NCT03840343 | Recruiting | Phase 1 | 2019 | AT-MSC | Autologous | 2.5 vs. 5 × 105 cells/kg body mass/ N = 2, 3 mo apart |
ia | ||
| Lupus Nephritis | |||||||||
| NCT00698191 | Completed | Phase 1|Phase 2 | 2007 | BM-MSC/UC-MSC | Allogeneic | 1 × 106 cells/kg body mass N = 1 |
iv | ↓ Proteinuria ↑ Disease improvement |
(24–26) |
| NCT01741857 | Completed | Phase 1|Phase 2 | 2012 | UC-MSC | Allogeneic | 1 × 106 cells/kg body mass N = 2, 7 d apart |
iv | ↓ Proteinuria ↑ Disease improvement |
(27) |
| NCT00659217 | Unknown status | Phase 1|Phase 2 | 2008 | BM-MSC | Autologous | NA N = 1 |
iv | ||
| NCT01539902 | Withdrawn | Phase 2 | 2012 | UC-MSC | Allogeneic | 5 × 107 N = 2, 7 d apart |
iv | ~ Remission rates in treated and placebo groups | (28) |
| NCT03580291 | Not yet recruiting | Phase 2 | 2018 | UC-MSC | Allogeneic | 2 × 106 cells/kg body mass N = 2, 7 d apart |
iv | ||
| NCT03458156 | Active, not recruiting | Phase 1 | 2017 | UC-MSC | Allogeneic | 1 × 106 cells/kg body mass N = 1 |
iv | ||
| NCT03174587 | Completed | Phase 1 | 2017 | BM-MSC | Allogeneic | 1, 2 and 3 × 106 cells/kg body mass⊲ N = 3 |
iv | No AE Infusion was tolerated |
(29) |
| NCT04522505 | Active, not recruiting | Phase 1 | 2017 | BM-MSC | Allogeneic | 1, 2, 3 and 106 cells/kg body mass⊲ N = 3 |
iv | ||
| NCT04835883 | Recruiting | Phase 2 | 2019 | BM-MSC | Allogeneic | 2 × 106 cells/kg body mass N = 2, 12 d apart |
iv | ||
| NCT04318600 | Completed | Phase 1 | 2014 | Amniotic-MSC | Allogeneic | 1 × 106 cells/kg body mass N = 3, monthly |
iv | ||
| NCT03917797 | Recruiting | Phase 2 | 2019 | UC-MSC | Allogeneic | NA | iv | ||
| NCT03673748 | Not yet recruiting | Phase 2 | 2021 | BM-MSC | Allogeneic | 1.5 × 106 cells/kg body mass N = 1 |
iv | ||
| NCT02633163 | Recruiting | Phase 2 | 2018 | UC-MSC | Allogeneic | 1 vs. 5 × 106 cells/kg body mass N = 1 |
iv | ||
| Kidney Transplant | |||||||||
| NCT00659620 | Unknown status | Phase 1|Phase 2 | 2008 | BM-MSC | Autologous | NA | iv | ||
| NCT00658073 | Completed | Phase 1 | 2008 | BM-MSC | Autologous | 1-2 × 106 cells/kg body mass N = 2, 24 h and 2 w after Tx |
iv | ↓ Acute Rejection ↓ Risk of opportunistic infections, ↑ eGFR 1-year follow-up |
(30) |
| NCT00734396 | Completed | Phase 1|Phase 2 | 2009 | BM-MSC | Autologous | 1 × 106 cells/kg body mass N = 1 |
iv | No AE Resolution of tubulitis without IF/TA in two patients |
(31) |
| NCT00752479 | Completed | Phase 1|Phase 2 | 2008 | BM-MSC | Allogeneic | 2 × 106 cells/kg body mass N = 1, 7 d post Tx |
iv | ↑ Serum Creatinine > Acute Graft Dysfunction ↑ Regulatory T cells ↓ Memory CD8+ T cells |
(32) |
| 2 × 106 cells/kg body mass N = 1, Tx |
iv | ↓ Memory CD8+ T cells ↓ Donor-specific CD8+ T cell cytolytic response ↑ Expansion of CD4+CD25+FoxP+ Treg cells |
(33) | ||||||
| NCT02012153 | Recruiting | Phase 1 | 2013 | BM-MSC | Autologous | 2 × 106 cells/kg body mass N = 1, 1 d before Tx |
iv | ↑ Graft function for 5 to 7 years follow-up ↓ CD8+ T cell in 3 of 4 patients ↓ex vivo T cell donor-specific cytotoxicity |
(34) |
| ↑ CD4+CD25+FoxP+ Treg cells ↑ Naïve and transitional B cells. 1 patient successfully discontinued immunotherapy with CsA |
|||||||||
| NCT02492490 | Unknown status | Phase 1|Phase 2 | 2014 | SVF | Autologous | 1 × 106 cells/kg body mass N = 4, 0, 7, 14, 21 d after Tx |
iv | ||
| NCT02561767 | Completed | Phase 1|Phase 2 | 2015 | BM-MSC | Autologous | 1 × 106 cells/kg body mass N = 4, 0, 7, 14, 21 d after Tx |
iv | No AE or SAE ↑ GFR. Renal function stable ↑ B cell levels |
(35) |
| NCT02563366 | Unknown status | Phase 1|Phase 2 | 2015 | BM-MSC | Allogeneic | 1 × 106 cells/kg body mass N = 4, 0, 7, 14, 21 d after Tx |
iv | ||
| NCT02490020 | Completed | Phase 1 | 2016 | UC-MSC | Allogeneic | iv: 2 × 106 cells/kg body mass, 48 h before Tx +/− ia: 5 × 106 cells/kg body mass, during Tx N = 2 |
iv + ia | No AE No MSC engraftment → Post-operative complications → eGFR |
(36, 37) |
| NCT02563340 | Unknown status | Phase 1|Phase 2 | 2015 | BM-MSC | Allogeneic | 1 × 106 cells/kg body N = 4, 2 w apart |
iv | ||
| NCT02492308 | Unknown status | Phase 1|Phase 2 | 2014 | SVF | Autologous | 1 × 106 cells/kg body N = 4, 0, 7, 14, 21 d after Tx |
iv | ||
| NCT02409940 | Completed | Phase 1 | 2013 | BM-MSC | Allogeneic/ Autologous | 0.2-3 × 106 cells/kg body N = 2, 1 d pre- and 30 d post-Tx |
iv | No AE or SAE ↑ Graft function ↑ CD4+CD25+FoxP+ Treg cells ↓ CD4+T cell proliferation |
(38, 39) |
| NCT02565459 | Recruiting | Phase 1 | 2015 | BM-MSC | Allogeneic | 1 vs. 2 × 106 cells/kg body mass N = 1, Tx |
iv | ||
| NCT02387151 | Completed | Phase 1 | 2015 | BM-MSC | Allogeneic | 1.5 - 2 × 106 cells/kg body mass N = 2 |
iv | (40) | |
| NCT02057965 | Active, not recruiting | Phase 2 | 2014 | BM-MSC | Autologous | 1 vs. 2 × 106 cells/kg body mass N = 2, 6 and 7 w after Tx |
iv | (41) | |
| NCT03478215 | Recruiting | Phase 2 | 2016 | BM-MSC | Autologous | 1, 2, and 3 × 106 cells/kg body mass⊲ N = 1 |
iv at surgery | ||
| NCT01429038 | Completed | Phase 1|Phase 2 | 2012 | BM-MSC | Allogeneic | 1.5 vs. 3 × 106 cells/kg body mass N = 2, 3 and 5 d post Tx |
iv | No MSC engraftment 2 Kidney/MSC HLA MM 1 MSC MM |
(42) |
MSC From Commercial Entities:
a
AC607 (AlloCure Inc.),
b
SBI-101 plasmapheresis device in combination with MSC (Sentien Biotechnologies Inc.),
c
Rexlemestrocel-L (Mesoblast Ltd.),
d
ORBCEL-MTM (Orbsen Therapeutics Lt.).
~, Similar; ↑, Increase; ↓, Decrease; ⊲, Dose-escalated study.
AE, Adverse events; AKI, Acute Kidney Injury; AT, Adipose Tissue; BM, Bone Marrow; CsA, Cyclosporin A; d, day; eGFR, estimated Glomerular Filtration Rate; GFR, Glomerular Filtration Rate; HLA, Human Leukocyte Antigen; ia, intra-arterial; IF, Interstitial fibrosis; iv, intra-venous; Kg, Kilogram; MM, Mismatch; mo, month; MSC, Mesenchymal Stromal Cell; NA, Not Available; SAE, Severe adverse events; SVF, Stromal Vascular Fraction; TA, Tubular Atrophy; Treg, Regulatory T cells; Tx, Transplant; UC, Umbilical Cord; w, week; y, year.