Table 1 Published clinical trials related to CD
No | Auto/Allo | Tissue of origin | No. of cells | Culture period | Delivery route | No. of patients | Efficacy | Proposed mode of action | Type of CD | Phase | Ref |
|---|---|---|---|---|---|---|---|---|---|---|---|
1 | Auto | BM | 2–10 × 106/kg | 14 ± 4 days | i.v. | 16 | 45% (5/11) clinical response (2 weeks) | Resetting immune functionalities | Luminal | Phase 1 | Dhere et al., 2016 [48] |
2 | Allo | BM | 3 × 106/kg | UNK | i.v. | 50 | 70% (21/30) complete clinical remission (2 months) | Inhibiting the inflammatory process and stimulating tissue regeneration by reducing proinflammatory cytokine productions at the inflamed site | Luminal | UNK | Knyazev et al., 2013 [49] |
3 | Allo | BM | 2 × 106/kg | UNK (less than P5) | i.v. | 16 | 80% (12/15) clinical response and 53% (8/15) clinical remission (42 days) | Immunopathogenic mechanism | Luminal | Phase 2 | Forbes et al., 2014 [50] |
4 | Allo | BM | 1.5–2.0 × 106/kg | 4 weeks | i.v. | 13 | 15% (2/13) clinical response (8 weeks), one of whom achieved clinical remission | Increasing NK cell proliferation, leading to MSC lysis, and/or decreasing the intestinal infiltration of NK/NKT cells | Luminal | Phase 1–2 | Gregoire et al., 2018 [51] |
5 | Allo | UC | 1 × 106/kg | UNK | i.v. | 82 | 0% (0/41) complete remission The CDAI, HBI, and CS dosage significantly decreased in the treated group compared with those in the control group | MSC therapy has moderate immunomodulatory effects | Luminal | Phase 1–2 | Zhang et al., 2018 [52] |
6 | Allo | BM | 1.5–2.0 × 108 (i.v.), 8 × 107 (i.l.) | UNK | i.v., i.l. | 36 | 67% (8/12) simple fistula healing (3 and 6 months) | Regulating immune response and reducing inflammation | Perianal fistulas | Phase 2 | Knyazev et al., 2020 [53] |
7 | Allo | BM | 1–9 × 107 | Over 2 weeks (maximally P3) | i.l. | 21 | 53% (8/15) fistula healing (6 weeks) Low-dose (1–3 × 107 cells) administration promoted perianal fistula healing | Immunosuppressive effects at the local site | Perianal fistulas | Phase 1–2 | Molendijk et al., 2015 [54] |
8 | Allo (Remestemcel-L) | BM | 1.5–3.0 × 108 | UNK | i.l. | 6 | 0% (0/4) clinical remission The simple endoscopic scores decreased by 71% (treated group) and increased by 61% (control group) (3 months) | No description | Luminal | Phase 1–2 | Lightner et al., 2022 [55] |
9 | Allo | BM | 7.5 × 107 | UNK (less than P5) | i.l. | 22 | 31% (4/13) (treated group) and 20% (1/6) (control group) complete clinical and radiographic healing (6 months) | No description | Peripouch fistulas | Phase 1–2 | Lightner et al., 2023 [56] |
10 | Allo | BM | 3 × 107 | 4 weeks (P3) | i.l. | 10 | 40% (4/10) complete resolution of the stricture (48 weeks) | Anti-inflammatory properties and anti-fibrotic effects | Luminal stricture | Phase 1–2 | Vieujean et al., 2022 [57] |
11 | Allo | BM | 7.5 × 107 | UNK (less than P5) | i.l. | 23 | 83% (15/18) (treated group) and 40% (2/5) (control group) complete clinical and radiographic healing (6 months) | No description | Complex perianal fistulas | Phase 1–2 | Lightner et al., 2023 [58] |
12 | Allo | AT | 2–4 × 107 | UNK | i.l. | 24 | 69% (9/13) reduction in draining fistulas, and 56% (9/16) complete closure of the treated fistula (24 weeks) | Reducing chronic inflammation in the fistula by immunomodulatory signals (anti-inflammation) and releasing trophic factors with regenerative properties (anti-fibrosis) | Complex perianal fistulas | Phase 1–2 | Portilla et al., 2013 [59] |
13 | Allo (Darvadstrocel) | AT | 1.2 × 108 | UNK | i.l. | 212 | 50% (53/107) (treated group) and 34% (36/105) (placebo group) combined remission (24 weeks) | Inducing IDO and subsequent degradation of tryptophan to kynurenine in the presence of inflammatory mediators (immunomodulatory effects) | Complex perianal fistulas | Phase 3 | Panés et at., 2016 [60] |
14 | Allo (Darvadstrocel) | AT | 1.2 × 108 | UNK | i.l. | 22 | 59% (13/22) and 68% (15/22) combined remission (24 and 52 weeks, respectively) | Inhibiting T cell function, increasing Treg, reducing proinflammatory cytokine production, and increasing anti-inflammatory cytokine production (i.e., immunomodulatory effects) | Complex perianal fistulas | Phase 3 | Furukawa et al., 2023 [61] |
15 | Allo (TH-SC01) | UC | 1.2 × 108 | 15 days before first passage (cells cultured to P5) | i.l. | 10 | 60% (6/10) combined remission, and 70% (7/10) clinical response (24 weeks) | Immunomodulatory functions | Complex perianal fistulas | Phase 1 | Wei et al., 2023 [62] |
16 | Auto | AT | 2 × 107 | UNK (3–6 days for culture in a bioreactor with matrix) | i.l. (with scaffold) | 12 | 83% (10/12) complete clinical healing and radiographic markers of response (6 months) | No description | Perianal fistulas | Phase 1 | Dietz et al., 2017 [63] |
17 | Auto | AT | 3.5 × 107 | UNK (placement of the MSC-coated plug after 6 weeks) | i.l. (with scaffold) | 5 | 60% (3/5) complete cessation of drainage, and 40% (2/5) reduction in drainage (6 months) | No description in the function of MSCs. An implantable matrix is used for sustained local exposure throughout the fistula tract | Rectovaginal fistulas | Phase 1 | Lightner et al., 2020 [64] |
18 | Auto | AT | 2 × 107 | UNK (placement of the MSC-loaded plug after 6 weeks) | i.l. (with scaffold) | 20 | 78% (14/18) complete clinical healing and 67% (12/18) MRI response (6 months) | Immunomodulatory functions of MSCs. An implantable matrix is used for sustained local exposure throughout the fistula tract | Complex perianal fistulas | Phase 1 | Dozois et al., 2023 [65] |