Molendijk 2015.

Study characteristics
Methods	Single centre (Leiden University Medical Center, the Netherlands), phase I‐II dose‐escalation study, randomised controlled trial conducted from June 2012 through July 2014.
Participants	Twenty‐one patients with refractory perianal fistulising Crohn’s disease were randomly assigned to three active groups and one placebo group. Eligible patients were men and women of at least 18 years of age with actively draining perianal fistulising Crohn’s disease refractory to conventional therapies. Eligible patients had to have 1‐2 internal openings and 1‐3 fistula tracts.
Interventions	The patients were randomly assigned to intervention or placebo. Intervention group: different doses of local injections of 1X107 (n = 5, group 1), 3X107 (n = 5, group 2), or 9X107 (n = 5, group 3) of allogenic mesenchymal stem cells (MSCs) into the wall of curettaged fistula, around the trimmed and closed internal opening. MSCs were extracted from 5 different donors from 50‐100 Bone marrow (BM) aspirates (1 donor /1 patient in each group) demineralised bone matrix (DMB) aspirate. Control group: placebo (n = 6) injected into the wall of curettaged fistula, around the trimmed and closed internal opening. Placebo (0.9% saline +human albumin with no cells). The placebo group received 0.9% NaCl/5% human albumin solution with no cells.
Outcomes	The primary outcome, fistula healing, was determined by physical examination 6, 12, and 24 weeks later; healing was defined as the absence of discharge and <2 cm of the fluid collection—the latter determined by MRI at week 12. 1ry safety endpoint: serious adverse events at 12 weeks. Efficacy: fistula healing and reduction of number at 12 weeks MRI at 12 weeks.
Notes	Additional criteria for inclusion were diagnosis of Crohn’s disease at least 3 months before enrollment, CDAI score of <250 at screening and baseline, a stable dose of current drugs (mesalamine and steroids 4 weeks; immunosuppressive drugs 8 weeks; anti‐TNF agents 8 weeks), which were continued during the entire study period. Trial start date: June 2012. Trial ending date: July 2014. Trial registry number: NCT01144962 Funding Source: Sponsors and collaborators: Leiden University Medical Center and DigestScience Foundation. Conflict of interest: the authors disclose no conflicts.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was performed at the Immunohematology and Blood Transfusion Department by a researcher who did not have any contact with or any knowledge about the included patients."
Allocation concealment (selection bias)	Low risk	The method of allocation was not stated: "Randomization was performed at the Immunohematology and Blood Transfusion Department by a researcher who did not have any contact with or any knowledge about the included patients." "Two weeks before the intervention was planned, the patient was randomized to receive either MSCs or placebo"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The placebo group received 0.9% NaCl/5% human albumin solution with no cells.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"Safety was assessed blindly by a physician by monitoring for (serious) adverse events and changes in vital signs at the time of surgical intervention with MSC or placebo injection at the day of treatment and at all follow‐up visits." "Routine laboratory measurements were performed and complications after surgery (e.g, bleeding, wound infection, and perianal abscesses) were assessed blindly at weeks 6, 12, and 24 by a surgeon other than the surgeon who performed the surgical intervention with MSC or placebo injection."
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT analysis was done. No missing data.
Selective reporting (reporting bias)	Low risk	Both primary and secondary outcomes match the protocol.
Other bias	Low risk	No differences between baseline charcteristics