Table 2B

Clinical trials of mesenchymal stromal cells in Crohn’s disease

Diseases and clinical trialsNumber of patients, source of cells, dose and route of administrationOutcomesComments
Crohn’s disease
 1. Garcia-Olmo et al (2005)82
 Phase I study
5 patients with fistulating Crohn’s disease received intralesional injections of autologous adipose derived at a dose of between 3 to 30×106 cells depending on yield.Six out of eight fistulae healed completely after 8 weeks. No adverse effectsFirst clinical trial of mesenchymal stem cells to treat Crohn’s disease. Cells were not cryopreserved. Study published before the ISCT criteria for MSC was set so cells were not assessed against the ISCT criteria.
 2. Garcia-Olmo et al (2009) 83
 Phase II multicentre randomised controlled trial
49 patients with complex fistulae. 24 received intralesional injection of 20×106 cells/kg allogeneic adipose derived stem cells; 25 received fibrin glue.Significantly better fistula healing in the treatment group (relative risk 4.43). Quality of life scores were also higher in the treatment group
 3. Duijvestein et al (2010)84
 Phase I study
9 patients with refractory Crohn’s disease received two IV infusions of 1–2×106 cells/kg autologous BM-derived MSCs 7 days apart.Well tolerated with few mild adverse events such as allergic reaction in a patient. Three patients showed improvement in Crohn’s disease activity indices 6 weeks post-treatmentThree patients required surgery due to worsening disease.
 4. Ciccocioppo et al (2011)85
 Phase I/II study in patients with fistulating Crohn’s disease
10 patients with refractory Crohn’s disease received intralesional injection of autologous BM-derived MSCs at a median dose of 20×106 cells every 4 weeks for a median four cycles (injections were stopped when patients achieved remission or exhausted supplies of autologous MSCs).Clinical improvement in all patients with seven achieving complete fistula closure and three achieving partial closure. Few adverse events were documented. Tregs also increased post-treatment and remained stable post follow-up.Cryopreserved cells were used
 5. Liang et al (2012)86
 Use of MSCs in inflammatory bowel diseases
7 patients with inflammatory bowel disease (4 Crohn’s, three ulcerative colitis) received IV infusion of allogeneic BM-derived or UC-derived MSCs at a dose of 1×106 cells/kg.Five patients achieved clinical remission at 3 months. Endoscopic improvement (assessed by endoscopic index of severity score) was also observed in three patients.Cryopreservation was not discussed
 6. de la Portilla et al (2013)87
 Phase I/IIa multicentre study
24 patients received intralesional injections of allogeneic adipose derived stem cells at a dose of 20×106 cells.More than half of patients showed healing of fistulae at 6 months. Up to 30% had complete fistula closureCryopreserved cells were used
 7. Forbes et al (2014)88
 Phase II open-label multicentre study
16 patients with refractory Crohn's disease received IV infusion of allogeneic MSCs at a dose of 2×106 cells/kg weekly for 4 weeks.Safe and well-tolerated. Clinical improvement observed in at least 12 patients, 8 of whom achieved clinical remission 42 days post-infusion.Cryopreserved cells were used
 8. Molendijk et al (2015)89
 Phase I/II double-blind, placebo-controlled, dose-escalating study
21 patients with refractory fistulating Crohn’s disease received intralesional injection of 1×107 or 3×107 or 9×107 allogeneic BM-derived MSC or placebo.Well tolerated. More significant fistulae healing in all dosing groups when compared with placebo. Most observed with 3×107 dose.Expanded half-products were cryopreserved until needed. Two weeks before treatment, they were thawed and further expanded to yield sufficient numbers of cells.
 9. Panés et al (2016)90
 Phase III randomised, double-blinded controlled study
212 treatment- refractory Crohn’s disease patients with fistulae. 107 Patients received 120×106 allogeneic adipose derived MSCs as a single intralesional dose, while 105 received placebo (saline).Significantly greater remission rates in the treatment group compared with the placebo group. Few adverse events notably proctalgia and anal abscess.First phase III study. Effective treatment option for Crohn’s disease patients that have failed conventional treatment options. Cryopreserved cells were used
 10. Dietz et al (2017)91
 Phase I trial of autologous stem cells applied in a bio-absorbable matrix
12 patients with fistula secondary to Crohn’s disease received autologous adipose-derived MSC embedded in a Gore Bio-A Fistula Plug through surgical insertion at a mean dose of 20×106 per plugProcedure was safely tolerated and few adverse events were reported. 75% of patients achieved complete healing at 3 months, while 83.3% achieved fistula closure at 6 months.Cryopreserved cells were used. Thawed cells were reincubated with a fistula plug in a polypropylene coated bioreactor for 3–6 days prior to surgery. This is the first combination of mesenchymal stromal cells in a biomaterial for local application in Crohn’s disease.
  • BM, bone marrow; MSCs, mesenchymal stromal cells; UC, umbilical cord.