Zhou 2020.

Study characteristics
Methods	Open‐label randomised‐ single centre in China (Nanjing Hospital of Chinese Medicine)
Participants	Patients with refractory Crohn's disease in the form of complicated anal fistula. Age from 12‐51 years (children included). Inclusion criteria: 1‐ Diagnosis of complex Crohn’s fistula‐in‐ano. 2‐ Patients with Crohn’s disease should control their disease in remission or mild active phase, that is, simplified CDAI is less than 6 points. 3‐ There is no evidence of cancer or precancerous lesions in enteroscopy 1 year before admission. 4‐ There are no other cardio‐cerebrovascular diseases. Exclusion criteria: 1‐ acute infection stage of anal fistula (immature fistula). 2‐ Patients with Crohn’s disease’s simplified CDAI > 6. 3‐ An autoimmune disease other than Crohn’s disease. 4‐ Patients with infectious diseases. 5‐ Patients who were allergic to anaesthetics.  6‐ Patients who cannot tolerate liposuction. 7‐ Patients who were pregnant or were trying to become pregnant.
Interventions	Intervention group: autologous adipose‐derived stem cell (ADSC). Fistula preparation: after admission, patients received fistula preparation more than 2 weeks before ADSC injection, which included fistula exploration, curettage, and drainage with seton. T5 × 106cells/mL per injection. Plus 1 × 106 cells/mL serum suspension perfused into the fistula. The dosage of ADSCs is based on the diameter and length of the fistula measured before injection, and mainly according to the results of preoperative MRI and clinical evaluation at fistula preparation. The diameter of the fistula was less than 1 cm, and 1 mL ADSCs/cm was injected into the fistula. And 2 mL ADSCs/cm was injected into the fistula in the patients with the fistula diameter ranging from 1 and 2 cm. The cells are prepared from Liposuction (AT) Control group: traditional incision thread‐drawing procedure.
Outcomes	Primary endpoint: Healing and closure of fistulas at months 3, 6, and 12. A minimum follow‐up of 24 weeks to evaluate the efficacy and safety of the ADSC.
Notes	Trial start date: Trial ending date: Trial registry number: ChiCTR1800014599 Funding Source: This study was funded by Key Medical Science and Technology Development Projects of Nanjing Commission of Health, No. ZKX17034. Conflict of interest: The authors declare that they have no competing interests.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	It is not stated in the study.
Allocation concealment (selection bias)	Unclear risk	It is not stated in the study.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Open‐label trial
Blinding of outcome assessment (detection bias) All outcomes	High risk	Open‐label trial
Incomplete outcome data (attrition bias) All outcomes	Low risk	Data up to 6 months ie. 24 weeks are present for all the patients: "All patients completed the 3‐month and 6‐month follow‐up but only 17 patients completed 12‐month follow‐up because another five received reoperation due to the recurrence and no healing of fistulas."
Selective reporting (reporting bias)	High risk	There are many differences between the protocol and the published manuscript. The authors stated in the protocol that is a case‐control study, yet they stated in their published paper that this is a randomized open‐label trial. The authors restricted the age of the studied patients in the protocol to >18 years of age, yet in the published manuscript they stated that the age of their patients ranged from 12‐51 years old. The authors stated that the sample size is 20 in control and 20 in intervention, yet in the published manuscript the total number of the studied population was 22.
Other bias	Unclear risk	The study included mainly male participants (21 males versus 1 female).

ADSC: adipose‐derived stem cell; ASCs: adipose‐derived stem cells; anti‐TNF: anti‐tumor necrosis factor; CDAI: Crohn’s Disease Activity Index; (Cx601) cells: allogeneic, expanded, adipose‐derived stem cells; GI: gastrointestinal; HSCT: Hematopoietic stem cell;  transplantation; IU: international unit; MRI: Magnetic resonance imaging; MSCs: mesenchymal stem cells; PDA‐001: human placenta‐derived cells; UC‐MSCs: expanded umbilical cord mesenchymal stem cells; NaCl: sodium chloride