Table 3.
Summarizes the Clinical Studies of MSCs in Treating IBD Completed in Recent Years
| Author, Time and Country | Phase | Clinical Indication | Number | SC Sources Route | Adjuvant Therapy | Follow-Up Period | Primary Outcomes | Ref. |
|---|---|---|---|---|---|---|---|---|
| Oyama Y. 2005, USA | I | Refractory CD | 12 | Auto-HSCs IV | CTX and equine ATG | 7–37 months | 11 patients entered a sustained remission, only 1 patient has developed a recurrence of active CD, which occurred 15 months after HSCT. | [170] |
| Burt R. K. 2010, USA | I | Severe CD | 24 | Auto-HSCs IV | CTX and equine ATG | 1–5 years | Eighteen of 24 patients are 5 or more years after transplantation. | [105] |
| Clerici M. 2011, Italy | N/A | Active moderate-severe CD | 7 | Auto-HSCs IV | CTX and rabbit ATG | 1 year | Most of whom showed clinical and endoscopic complete remission and were maintained for one year. | [171] |
| Hasselblatt P. 2012, Germany | I/II | Refractory CD | 12 | Auto-PBSCs IV | High-dose CTX | 0.5–10.3 years | 5 patients achieved a clinical and endoscopic remission within 6 months after auto-PBSCT. 7/9 relapses patients reduced maintenance dose of conventional drugs. |
[172] |
| Hawkey C J. 2015, United Kingdom | III | Refractory CD | 45 | Auto-HSCs IV | High-dose CTX | 1 year | Compared with conventional therapy, did not result in a statistically significant improvement in sustained disease remission at 1 year. | [107] |
| Kotlarz D. 2012, Germany | II | IBD with IL-10 gene defect | 66 | Allo-HSCs IV | Lemtrada F-ara-A treosulfan | 2 years | Allo-HSCT was performed in 5 patients to induce sustained clinical remission. | [173] |
| Liang J. 2012, China | N/A | Refractory IBD 4 CD, 3 UC | 7 | Allo-MSCs IV | Steroids and/or immunosuppressants | Mean 19 months | Diarrhea frequency and abdominal pain/cramps gradually improved in all the seven patients, and the index score decreases. | [174] |
| Forbes G. M. 2013 Australia | II | Luminal CD | 16 | Allo-MSCs Local | Corticosteroid, AZA | 42 days | In a phase 2 study, administration of allogeneic MSCs reduced CDAI and CDEIS scores in patients with refractory luminal CD. | [112] |
| GarciaOlmo D. 2003, Spain | II | RFCD | 1 | ASCs Local | Olsalazine | 3 months | Since the surgical procedure 3 month ago the patient has not experienced vaginal flatus or fecal incontinence through her vagina. | [175] |
| GarciaOlmo D. 2009, Spain | II | Complex PFCD | 24 | ASCs Local | Fibrin glue | 1 year | Combination therapy appears to achieve higher rates of healing than fibrin glue alone. | [176] |
| Guadalajara H. 2011, Spain | II | PFCD | 49 | ASCs Local | Fibrin glue | 3 years | A low proportion of the stem cell-treated patients with closure after the procedure. Remained free of recurrence after more than 3 years of follow-up. | [177] |
| Herreros M. D. 2012, Spain | III | Complex Anal fistula | 200 | ASCs Local | Fibrin glue | 1 year | Achieving healing rates of approximately 40% at 6 months and of more than 50% at 1-year follow-up. | [178] |
| Dietz A. B. 2017 USA | I | Perianal CD | 12 | Auto-ASCs. Local | Nothing | <6 month | 10/12 (83%) achieved combined remission at 24 weeks by fistula exam and MRI. | [179] |
| Dige A. 2019 Denmark | I | Perianal CD | 21 | Auto-ASCs. Repeatable Local |
Nothing | <6 month | 12/21 (57%) achieved clinical remission 6 months after last injection. 8/9 patient who underwent MRI had complete resolution at 6 months. |
[180] |
| Lightner A. L. 2020 USA | I | Rectovaginal CD | 5 | Auto-ASCs. Local |
Nothing | <6 month | 3/5 (60%) with complete clinical response. 2/5 (40%) with partial clinical response. 0/5 patients with radiographic remission |
[181] |
| Nikolic M. 2021 Austria | I | Rectovaginal CD | 4 | Allo-ASCs. Local | Nothing | <6 month | Fistula closure and absence of drainage on exam at 6 months. 1/4 (25%) achieved clinical healing at 6 months. | [182] |
| Cho Y. B. 2015, Korea | II | Perianal CD | 41 | Auto-ASCs. Local | Nothing | >6 month | At 24 months, complete healing was observed in 21/26 (80.8%) patients in mPP group and 27/36 (75%) in mITT group. | [183] |
| Ciccocioppo R. 2015, Italy | I | Perianal CD | 10 | Auto-BM-MSCs. Local | Nothing | >6 month | Fistula relapse-free survival was 88% at 1 year, 50% at 2 years, and remaining at 37% for the remainder of the six-year follow-up. Mean CDAI score decreased from 300 to 150 at 6 years. |
[184] |
| Garcia-Olmo D. 2015, Spain | I | CD (3 with Perianal CD) | 10 | Auto-ASCs. Local / IV. | Nothing | >6 month | 2/3 (66%) of CD patients achieved complete healing (re-epithelialization and absence of suppuration at 1 year) at 1 year. | [185] |
| Park K. J. 2016, Korea | I | Perianal CD | 6 | Auto-ASCs. Local | Nothing | >6 month | 2/3 (66.7%) in group 1 and 1/3 (33.3%) in group 2 achieved clinical healing at 8 months. | [186] |
| García-Arranz M. 2016, Spain | I/II | Rectovaginal CD | 10 | Auto-ASCs. Local | Nothing | >6 month | Of 5 total patients who completed study, 3 achieved clinical healing (60%) (re-epithelialization of both vaginal and rectal sides and absence of drainage) at 52 weeks. | [187] |
| Panés J. 2018 Austria | III | Perianal CD | 212 | Auto-ASCs (107 Local) Placebo (105) |
Nothing | >6 month | Using mITT, 58/103 (56.3%) of patients in treatment arm achieved combined remission (absence of external openings on exam and absence of collections > 2 cm on MRI) vs 39/101 (38.6%) in control arm at week 52. | [157] |
| Wainstein C. 2018, Chile | I | Perianal CD | 9 | Auto-ASCS Local | Nothing | >6 month | 8/9 (88.9%) patients with complete healing (absence of suppuration from the external fistula opening and complete epithelialization), 1/9 (11.1%) patients with partial healing at median follow-up of 31 months. | [188] |
| Knyazev O. V. 2018 Russia | II | Perianal CD | 36 | Auto-BM-MSCs Local | Nothing | >6 month | At 3 and 6 months, healing of 66.6% (8/12) in group 1, 60% (6/10) in group 2, and 7.14% (1/14) in group 3. At 1-year, healing of 58.3% (7/12) in group 1, 60% (6/10) in group 2, and 14.3% (2/14) in group 3. |
[189] |
| Herreros M. D. 2019, Spain | I/II | CD (18 with perianal CD) | 45 | Auto-ASCs allo-ASCs Local / IV |
Nothing | >6 month | 55.5% of CD patients achieved healing (absence of suppuration). CD patients receiving SVF, auto-ASCs and allo-ASCs were cured by 40%, 66.6% and 55.5% respectively. |
[190] |
| Barnhoorn M. C. 2020, The Netherlands | I | Perianal CD | 21 | Auto-BM-MSCs Local | Nothing | >6 month | Group 1: 3/4 (75%) healing at 4 years. Group 2: 4/4 (100%) healing at 4 years. Group 3: 2/5 (20%) healing at 4 years. Group 4: 0/3 (0%) healing at 4 years. |
[145] |
| Zhou C. 2020, China | II | Perianal CD | 22 | Auto-ASCs Local | Nothing | >6 month | 3 months: 10/11 (91%) in treatment arm vs 5/11 (45.5%) in placebo arm. 6 months: 8/11 (72.7%) in treatment arm vs 6/11 (54.5%) in placebo arm. 12 months: 7/11 (63.6%) in treatment arm vs 6/11 (54.5%) in placebo arm. |
[191] |
| Laureti, S. 2020, Italy | II | Perianal CD | 15 | ASCs Lipogems® Local | Nothing | >6 month | 10/15 (66.7%) with combined remission (closure of all external openings on exam and absence of collections > 3mm on MRI) at 24 months. | [192] |
| Melmed G. Y. 2015, Italy | Ib/IIa | Luminal CD | 50 | PDA-001 1U, 4U IV |
Nothing | >6 month | Decrease in CDAI by ≥100 points and/or 25% from baseline at weeks 4 and 6. Phase I b: primary efficacy not reported Phase IIb: Placebo: 0/16 1U PDA-001: 5/15 (33%) 4U PDA-001: 5/13 (38.5%) |
[193] |
| Dhere T. 2016, USA | I | Luminal CD | 12 | Auto- BM-MSCs IV | N/A | >6 month | 5/11 (45.4%) achieved clinical response (decrease in CDAI by ≥ 100 points at 2 weeks). | [194] |
| Hu J. 2016, China | I/II | With UC | 70 | UCBSCs IV | N/A | >6 month | 29/34 (85.3%) with clinical response (decrease in total Mayo UC activity score of ≥3 and ≥30% from baseline) in group I vs 6/36 (16.7%) at 3 months. | [154] |
| Knyazev O. V. 2016 Russia | I | With UC | 22 | Auto-BM-MSCs IV | AZA | >6 month | Remission rate of 50% (6/12) in treatment group vs 10% (1/10) in control group at 3 years. Remission duration of 22 months in treatment group vs 20 months in control group at 3 years. |
[195] |
| Gregoire C. 2018 Belgium | I/II | Luminal CD | 13 | Auto-BM-MSCs IV. | N/A | >6 month | 2/13 (15.4%) with clinical response (decrease in CDAI by ≥100 points) at 8 weeks. | [153] |
| Zhang J. 2018, China | I | Luminal CD | 82 | UCBSCs IV. | Corticosteroid | >6 month | Decrease in CDAI, HBI, and corticosteroid usage. | [111] |
| Knyazev O V. 2018 Russia | I/II | Luminal CD | 34 | BM-MSCs IV. | AZA | >6 month | Clinical remission (CDAI < 150) at 12 months. | [113] |
Abbreviations: Allo, Allogeneic; ASCs, adipose mesenchymal stem cells; Auto, Autogenous; BM-MSCs, Bone marrow mesenchymal stem cells; CD, Crohn’s disease; CDAI, Crohn’s disease activity index; CDEIS, Crohn’s Disease Endoscopic Index of Severity; HBI, Harvey-Bradshaw index; HSCT, hematopoietic stem cell transplantation; IBD, Inflammatory bowel disease; IL-10, interleukin-10; IP, intraperitoneal injection; IV, intravenous injection; mPP, Massively Parallel Processing; MRI, Magnetic resonance imaging; MSCs, mesenchymal stem cells; MSCT, mesenchymal stem cells transplantation; PBSCT, Peripheral blood stem cell transplantation; PDA-001, Human placenta-derived cells; PFCD, perianal fistula Crohn’s disease; RFCD, rectovaginal fistula CD; SCs, stem cells; SVF, Stromal Vascular Fraction; UC, Ulcerative colitis; UCBSCs, Umbilical Cord Blood stem cells; CTX, Cyclophosphamide; ATG, antithymocyte globulin; F-ara-A, fludarabine; AZA, azathioprine; N/A, Not provided.