• Adverse effects
• Anal fistulas
• Healing
• Stem cells
• Systematic review

• Humans
• Rectal Fistula/therapy
• Rectal Fistula/etiology
• Rectal Fistula/surgery
• Stem Cell Transplantation/methods
• Stem Cell Transplantation/adverse effects
• Treatment Outcome
• Male
• Adipose Tissue/cytology
• Female
• Wound Healing
• Crohn Disease/complications
• Adult
• Middle Aged
• Randomized Controlled Trials as Topic

• Crohn’s disease
• Extracellular vesicles
• IBD
• Mesenchymal stem cell
• Perianal fistulas

• Humans
• Rectal Fistula/therapy
• Rectal Fistula/etiology
• Crohn Disease/complications
• Male
• Female
• Adult
• Exosomes/transplantation
• Magnetic Resonance Imaging
• Treatment Outcome
• Middle Aged
• Mesenchymal Stem Cell Transplantation/methods
• Mesenchymal Stem Cells/cytology
• Young Adult

• efficacy
• fistula
• meta-analysis
• stem cell therapy
• systematic review
• treatment

• Humans
• Stem Cell Transplantation/methods
• Stem Cell Transplantation/adverse effects
• Systematic Reviews as Topic
• Fistula/therapy
• Treatment Outcome

• Crohn's disease
• exosomes
• nanomedicine
• ulcerative colitis

• Humans
• Extracellular Vesicles/metabolism
• Extracellular Vesicles/transplantation
• Inflammatory Bowel Diseases/therapy
• Inflammatory Bowel Diseases/metabolism
• Mesenchymal Stem Cells/metabolism
• Animals

• PID2021-122636OB-I00 Ministerio de Ciencia y Educación
• European Union
• PI20/00420 Instituto de Salud Carlos III
• CB06_04_0034 Centro de Investigación Biomédica en Red
• RYC2013-13186 Centro de Investigación Biomédica en Red
• ERDF
• 100008ID1 INVESTIGO-AGAUR
• 100036TC2 INVESTIGO-AGAUR
• CB06_04_0034 Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
• European Union
• Instituto de Salud Carlos III
• ERDF
• Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas

• Fistula
• Magnetic resonance imaging
• Rectal fistula
• Stem cell
• Wound healing

• Adipose tissue
• Adult stem cells
• Anal fistula
• Recurrent
• Regenerative medicine

• Humans
• Male
• Female
• Rectal Fistula/therapy
• Rectal Fistula/surgery
• Middle Aged
• Adult
• Adipose Tissue/transplantation
• Prospective Studies
• Recurrence
• Treatment Outcome
• Transplantation, Autologous
• Injections
• Anal Canal/surgery

• Humans
• Male
• Adult
• Middle Aged
• Female
• Treatment Outcome
• Tertiary Care Centers
• Anal Canal/surgery
• Rectal Fistula/surgery
• Retrospective Studies
• Crohn Disease/complications

• Complex
• Fistula-in-ano
• Healing
• Incontinence
• Sphincter preserving

• Humans
• Fecal Incontinence/etiology
• Fecal Incontinence/surgery
• Wound Healing
• Anal Canal/surgery
• Ligation/adverse effects
• Rectal Fistula/surgery
• Rectal Fistula/etiology
• Treatment Outcome

• University of Otago

• Complex perianal fistula
• Long-term evaluation
• Mesenchymal stem cells
• Meta-analysis

• Anorectal
• Autologous fat grafting
• Fistula

• Clinical trials
• Efficacy and safety
• Healing rate
• Mesenchymal stem cells transplantation
• Perianal fistulas
• Randomised controlled trial
• Systematic review and meta-analysis

• Humans
• Quality of Life
• Mesenchymal Stem Cell Transplantation/methods
• Treatment Outcome
• Mesenchymal Stem Cells
• Rectal Fistula/therapy
• Crohn Disease/therapy

• The National Natural Science Foundation of China
• The Changchun Scientific and Technological Development Program
• Life Spring AKY Pharmaceuticals
• The Jilin Scientific and Technological Development Program

• Adult
• Humans
• Rectal Fistula/surgery
• Treatment Outcome
• Anus Diseases/surgery
• Laser Therapy
• Low-Level Light Therapy
• Meta-Analysis as Topic
• Systematic Reviews as Topic

• National Natural Science Foundation of China
• a grant from Siming Scholars from Shuguang Hospital
• Clinical Research Plan of SHDC

Adipose-derived stem cells (ADSCs) have provided promising applications for Crohn’s disease (CD). However, the practical efficacy of ADSCs remains controversial, and their mechanism is still unclear. Based on the pathogenesis of dysregulated immune responses and abnormal lymphatic alterations in CD, vascular endothelial growth factor-C (VEGF-C) is thought to be a favourable growth factor to optimize ADSCs. We aimed to investigate the efficacy of VEGF-C-stimulated ADSCs and their dual mechanisms in both inhibiting inflammation “IN” and promoting inflammation “OUT” in the intestine.

Human stem cells isolated from adipose tissues were identified, pretreated with or without 100 ng/ml VEGF-C and analysed for the secretion of cell culture supernatants in vitro. Lymphatic endothelial cells (LECs) were treated with ADSCs-conditioned medium or co-cultured with ADSCs and VEGF-C stimulated ADSCs. Changes in LECs transmigration, and VEGF-C/VEGFR-3 mRNA levels were assessed by transwell chamber assay and qRT–PCR. ADSCs and VEGF-C-stimulated ADSCs were intraperitoneally injected into mice with TNBS-induced chronic colitis. ADSCs homing and lymphatic vessel density (LVD) were evaluated by immunofluorescence staining. Lymphatic drainage was assessed using Evans blue. Cytokines and growth factors expression was detected respectively by ELISA and qRT–PCR. The protein levels of VEGF-C/VEGFR-3-mediated downstream signals and the NF-κB pathway were assayed by western blot. Faecal microbiota was measured by 16S rRNA sequencing.

ADSCs stimulated with VEGF-C released higher levels of growth factors (VEGF-C, TGF-β1, and FGF-2) and lower expression of cytokines (IFN-γ and IL-6) in cell supernatants than ADSCs in vitro (all P < 0.05). Secretome released by VEGF-C stimulated ADSCs exhibited a stronger LEC migratory capability and led to elevated VEGF-C/VEGFR-3 expression, but these effects were markedly attenuated by VEGFR-3 inhibitor. VEGF-C-stimulated ADSCs homing to the inflamed colon and mesenteric lymph nodes (MLNs) can exert stronger efficacy in improving colitis symptoms, reducing inflammatory cell infiltration, and significantly enhancing lymphatic drainage. The mRNA levels and protein concentrations of anti-inflammatory cytokines and growth factors were markedly increased with decreased proinflammatory cytokines in the mice treated with VEGF-C-stimulated ADSCs. Systemic administration of VEGF-C-stimulated ADSCs upregulated the colonic VEGF-C/VEGFR-3 pathway and activated downstream AKT and ERK phosphorylation signalling, accompanied by decreased NF-κB p65 expression. A higher abundance of faecal p-Bacteroidetes and lower p-Firmicutes were detected in mice treated with VEGF-C-stimulated ADSCs (all P < 0.05).

VEGF-C-stimulated ADSCs improve chronic intestinal inflammation by promoting lymphatic drainage and enhancing paracrine signalling via activation of VEGF-C/VEGFR-3-mediated signalling and inhibition of the NF-κB pathway. Our study may provide a new insight into optimizing ADSCs treatment and investigating potential mechanisms in CD.

The online version contains supplementary material available at 10.1186/s13287-022-03132-3.

• Adipose derived-stem cells
• Chronic colitis
• Faecal microbiota
• Lymphatic drainage
• Paracrine
• Vascular endothelial growth factor C

• Chronic Disease
• Culture Media, Conditioned/pharmacology
• Humans
• Inflammatory Bowel Diseases/therapy
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells

• Abscess/surgery
• Anus Diseases
• Colon
• Female
• Humans
• Rectal Fistula/surgery
• Rectovaginal Fistula/surgery
• Surgeons

MSCs products as well as their derived extracellular vesicles, are currently being explored as advanced biologics in cell-based therapies with high expectations for their clinical use in the next few years. In recent years, various strategies designed for improving the therapeutic potential of mesenchymal stromal cells (MSCs), including pre-conditioning for enhanced cytokine production, improved cell homing and strengthening of immunomodulatory properties, have been developed but the manufacture and handling of these cells for their use as advanced therapy medicinal products (ATMPs) remains insufficiently studied, and available data are mainly related to non-industrial processes. In the present article, we will review this topic, analyzing current information on the specific regulations, the selection of living donors as well as MSCs from different sources (bone marrow, adipose tissue, umbilical cord, etc.), in-process quality controls for ensuring cell efficiency and safety during all stages of the manual and automatic (bioreactors) manufacturing process, including cryopreservation, the use of cell banks, handling medicines, transport systems of ATMPs, among other related aspects, according to European and US legislation. Our aim is to provide a guide for a better, homogeneous manufacturing of therapeutic cellular products with special reference to MSCs.

• Cell- and Tissue-Based Therapy
• Extracellular Vesicles
• Mesenchymal Stem Cells
• Treatment Outcome
• Umbilical Cord

• Anal fistula
• Fistulotomy
• Incontinence
• Ligation of intersphincteric fistula tract
• Recurrence
• Transanal opening of intersphincteric space

The optimal treatment of complex anal fistulas remains unclear, though many different sphincter-preserving procedures have been described. A minimally invasive technique with a better outcome is desired. The purpose of this study was to present a new technique—sphincter-preserving fistulectomy (SPF) and its clinical outcomes.

A retrospective study was performed to compare the efficacy and outcomes of SPF with ligation of the intersphincteric fistula tract (LIFT) in the management of complex anal fistulas in regards to postoperative pain, complications, wound healing time, recurrence, overall success rate, fecal continence function, and quality of life. Continence function was evaluated using the Wexner incontinence scale and anal manometry. The fecal incontinence quality of life (FIQL) scale was used to assess patients' quality of life.

From June 2020 to July 2021, 41 patients with 43 SPF procedures and 35 patients with 35 LIFT procedures were included. Postoperative pain was comparable between two groups. The morbidity rate and the mean wound healing time in the SPF group were lower than those in the LIFT group (2.3% vs. 48.6%, p < 0.001; 1.4 ± 0.3 vs. 1.7 ± 0.4 months, p = 0.001). At a mean follow-up duration of 11.4 ± 3.5 months in the SPF group and 10.7 ± 4.3 months in the LIFT group, SPF achieved a better overall success rate than LIFT (97.7% vs. 77.1%, p = 0.014). Three patients in the SPF group and 4 patients in the LIFT group who all underwent a simultaneous fistulotomy procedure complained new incontinence of flatus. There was no statistical difference between the two groups in regards to the Wexner scores (p = 0.790), the maximum resting anal canal pressure (p = 0.641), the maximum squeeze pressure (p = 0.289), and the FIQL scores including lifestyle (p = 0.188), coping (p = 0.188), depression (p = 0.850), and embarrassment (p = 0.910).

SPF is a novel, safe, and effective minimally invasive technique for the management of complex anal fistulas, with a promising success rate and negligible impairment on continence. Future prospective studies are needed to evaluate the long-term outcomes of SPF.

Anal fistula is a common disease that needs surgical treatment to be resolved. Despite a variety of surgical options, the major problem is still to cure complex fistulas without any recurrence in the long-term follow-up but, at the same time, to avoid an impairment of continence. In recent years, one solution has been the application of mesenchymal stem cells derived from adipose tissue, especially in association with other treatments, such as the use of fibrin glue or the previous application of a seton. Their initial use in fistulas associated with Crohn's disease has shown encouraging results. In this non-systematic review our aim is to analyze the use in cryptoglandular fistulas: the rate of healing is not so high, and the number of studies is limited. Therefore, further randomized controlled trials are needed to establish their efficacy in the case of complex cryptoglandular anal fistulas and their possible complications.

There are many surgical methods of sphincter preservation in treating complex anal fistula, but the therapeutic effects of each operation are different. Therefore, this study aimed to compare the impact of other treatment methods through a network meta-analysis to evaluate the best sphincter preservation method for treating complex anal fistula.

We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Journal Database, and the Wanfang Database to collate randomized controlled trials on sphincter-preserving surgery for complex anal fistula.

A total of 29 articles were included in this meta-analysis. The cure rates showed no statistically significant differences between any two interventions (P > 0.05). The recurrence rate results showed that the rate of patients after Fistulectomy was higher than others (P < 0.05). The incidence rate of complications showed that the incidence rate after fistulectomy treatment was higher than that of others (P < 0.05). The surface under the cumulative ranking (SUCRA) was used to arrange their advantages and disadvantages, and a larger SUCRA value indicates that the intervention may be more effective. The results showed that TROPIS may have the highest cure rate (SUCRA = 78.6%), stem cell transplantation (SCT) may have the lowest recurrence rate (SUCRA = 85.5%), and imLIFT may have the least complications (SUCRA = 88.2%).

According to the existing literature data, for patients with complex anal fistula, TROPIS may be the surgical method with the highest cure rate, SCT may be the treatment method with the lowest recurrence rate, and imLIFT may be the surgical method with the lowest incidence of postoperative complications.

PROSPERO, identifier: CRD42020221907.

Injection of autologous adipose tissue (AT) has recently been demonstrated to be an effective and safe treatment for anal fistulas. AT mesenchymal stem cells (AT-MSCs) mediate the healing process, but the relationship between molecular characteristics of AT-MSCs of the injected AT and fistula healing has not been adequately studied. Thus we aimed to characterize the molecular and functional properties of AT-MSCs isolated from autologous AT injected as a treatment of cryptogenic high transsphincteric perianal fistulas and correlate these findings to the healing process.

27 patients (age 45 ± 2 years) diagnosed with perianal fistula were enrolled in the study and treated with autologous AT injected around the anal fistula tract. AT-MSCs were isolated for cellular and molecular analyses. The fistula healing was evaluated by MRI scanning after 6 months of treatment. AT-MSC phenotype was compared between responders and non-responders with respect to fistula healing.

52% of all patients exhibited clinical healing of the fistulas as evaluated 6 months after last injection. Cultured AT-MSCs in the responder group had a lower short-term proliferation rate and higher osteoblast differentiation potential compared to non-responder AT-MSCs. On the other hand, adipocyte differentiation potential of AT-MSCs was higher in non-responder group. Interestingly, AT-MSCs of responders exhibited lower expression of inflammatory and senescence associated genes such as IL1B, NFKB, CDKN2A, TPB3,TGFB1.

Our data suggest that cellular quality of the injected AT-MSCs including cell proliferation, differentiation capacity and secretion of proinflammatory molecules may provide a possible mechanism underlying fistula healing. Furthermore, these biomarkers may be useful to predict a positive fistula healing outcome.

Trial registration: NTC04834609, Registered 6 April 2021. https://clinicaltrials.gov/ct2/show/NCT04834609

The online version contains supplementary material available at 10.1186/s13287-021-02644-8.

• Adipose-derived mesenchymal stem cells
• Autologous adipose tissue graft injection
• Fistula healing
• Stem cell potency
• Transsphincteric perianal fistula

Between 20 to 25% of Crohn’s disease (CD) patients suffer from perianal fistulas, a marker of disease severity. Seton drainage combined with anti-TNFα can result in closure of the fistula in 70 to 75% of patients. For the remaining 25% of patients there is room for in situ injection of autologous or allogenic mesenchymal stem cells such as adipose-derived stem/stromal cells (ADSCs). ADSCs exert their effects on tissues and effector cells through paracrine phenomena, including the secretome and extracellular vesicles. They display anti-inflammatory, anti-apoptotic, pro-angiogenic, proliferative, and immunomodulatory properties, and a homing within the damaged tissue. They also have immuno-evasive properties allowing a clinical allogeneic approach. Numerous clinical trials have been conducted that demonstrate a complete cure rate of anoperineal fistulas in CD ranging from 46 to 90% of cases after in situ injection of autologous or allogenic ADSCs. A pivotal phase III-controlled trial using allogenic ADSCs (Alofisel^®) demonstrated that prolonged clinical and radiological remission can be obtained in nearly 60% of cases with a good safety profile. Future studies should be conducted for a better knowledge of the local effect of ADSCs as well as for a standardization in terms of the number of injections and associated procedures.

• Crohn’s disease
• adipose-derived stem cells
• allogenic stem cells
• mesenchymal stem cells
• perianal fistula

• Adipose Tissue/cytology
• Animals
• Clinical Trials as Topic
• Crohn Disease/complications
• Crohn Disease/therapy
• Humans
• Rectal Fistula/complications
• Rectal Fistula/therapy
• Stem Cell Transplantation
• Stem Cells/cytology

Polytrauma is a major clinical problem due to its impact on morbidity and mortality, especially among the younger population. Its pathophysiology is not completely elucidated, and the study of the involvement of certain cell populations with therapeutic potential, such as mesenchymal stromal cells (MSCs), is an area of growing interest, as mesenchymal cells have anti-inflammatory, immunoregulatory, and osteogenic potential.

In the present preliminary work, we have evaluated the characteristics of MSCs in terms of proliferation, immunophenotype, cell cycle, clonogenic capacity, and multilineage differentiation ability in a series of 18 patients with polytrauma and compared them to those from otherwise healthy patients undergoing elective spinal surgery.

MSCs from polytrauma patients displayed higher proliferative potential with significantly higher cumulative population doublings, increased expression of some important cell adhesion molecules (CD105, CD166), and an early pre-osteogenic differentiation ability compared to those of the control group.

MSCs could potentially be of help in the repair process of polytrauma patients contribute to both cell-tissue repair and anti-inflammatory response. This potential should be further explored in larger studies.

The online version contains supplementary material available at 10.1186/s13287-021-02500-9.

• Bone regeneration
• Cellular therapy
• MSC
• Mesenchymal stem cells
• Mesenchymal stromal cells
• Polytrauma

Cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery. A fistula is typically defined as a pathological communication between two epithelialized surfaces. More specifically, perianal fistula manifests as an abnormal tract between the anorectal canal and the perianal skin. Perianal fistulas are often characterized by significantly decreased patient quality of life. The cryptoglandular theory of perianal fistulas suggests their development from the proctodeal glands, which originate from the intersphincteric plane and perforate the internal sphincter with their ducts. Involvement of proctodeal glands in the inflammatory process could play a primary role in the formation of cryptoglandular perianal fistula. The objective of this narrative review was to investigate the current knowledge of the pathogenesis of cryptoglandular perianal fistula with the specific aims of characterizing the potential role of proinflammatory factors responsible for the development of chronic inflammation. Further studies are crucial to improve the therapeutic management of cryptoglandular perianal fistulas.

• Cryptoglandular perianal fistula
• adipokines
• cytokines
• pathogenesis
• proctodeal glands
• proinflammatory factors

Multipotent mesenchymal stromal cells (MSCs) are currently the most extensively studied type of adult stem cells in advanced stages of development in the field of regenerative medicine. The biological properties of MSCs have generated great hope for their therapeutic use in degenerative and autoimmune conditions that, at present, lack effective treatment options. Over the last decades, MSCs have been typically obtained from adult bone marrow, but the extraction process is highly invasive and the quality and numbers of isolated cells is drastically influenced by patient age, medication and associated comorbidities. Therefore, there is currently an open discussion on the convenience of allogeneic over autologous treatments, despite potential disadvantages such as rejection by the host. This shift to the allogeneic setting entails the need for high production of MSCs to ensure availability of sufficient cell numbers for transplantation, and therefore making the search for alternative tissue sources of highly proliferative MSC cultures with low levels of senescence occurrence, which is one of the greatest current challenges in the scale up of therapeutic cell bioprocessing. Herein we (i) present the main isolation protocols of MSCs from bone marrow, adipose tissue and Wharton’s jelly of the umbilical cord; and (ii) compare their qualities from a bioprocess standpoint, addressing both quality and regulatory aspects, in view of their anticipated clinical use.

• Adipose tissue
• Bone marrow
• MSCs isolation protocols
• Multipotent mesenchymal stromal cells
• Umbilical cord
• Wharton’s jelly

• Anal fistula
• Fistulotomy
• Incontinence
• Recurrence
• Surgery

• Crohn’s fistula
• Healing rate
• Stem cells
• Treatment-related adverse events

• HPV
• Prognosis
• Relapse-free survival
• Tongue cancer stem cells
• Tongue squamous cell carcinoma

• advanced therapies
• allogeneic adipose-derived mesenchymal stromal cells
• bioengineered dermis
• recalcitrant ulcers
• tissue engineering

Complex cryptoglandular perianal fistula (CPAF) is a kind of anal fistula that may cause anal incontinence after surgery. Minimally invasive surgery of anal fistula is constantly emerging. Over the past 20 years, there are several sphincter-sparing surgeries, one of which is autologous adipose-derived stem cell (ADSC) transplantation. However, to date, there is no study regarding the treatment of complex CPAF with ADSC in China. This is the first study in China on the treatment of complex CPAF with ADSC to evaluate its safety and efficacy.

Totally, 24 patients with complex CPAF were enrolled in this prospective case-control study from January 2018 to December 2019 in the National Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine. Patients were divided into ADSC group and endorectal advancement flap (ERAF) group according to their desire. The healing of fistulas (healing of all treated fistulas at baseline, confirmed by doctor’s clinical assessment and magnetic resonance imaging or transrectal ultrasonography) was evaluated at week 12 after treatment. In addition to their safety evaluation based on adverse events monitored at each follow-up, the patients were also asked to complete some scoring scales at each follow-up including pain score with visual analog score (VAS) and anal incontinence score with Wexner score.

The closure rates within ADSC group and ERAF group at week 12 were 54.55% (6/11) and 53.85% (7/13), respectively, without significant difference between them. VAS score in ADSC group was significantly lower than that in ERAF group at the 5th day postoperatively [1(0,2) VS 2(2,4), p = 0.011], but no differences were observed at the other time. Wexner score of all patients was not increased with no significant differences between the two groups. Adverse events were observed fewer in ADSC group (27.27%) than that in ERAF group (53.85%), but there was no significant difference between them.

This study indicated safety and efficiency of ADSC for the treatment of complex CPAF in the short term, which is not inferior to that of ERAF. ADSC may provide a promised and potential treatment for complex CPAF conforming to the future of the treatment, which is reconstruction and regeneration.

ChiCTR, ChiCTR1800014599. Registered 23 January 2018—retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=24548

• Autologous adipose-derived stem cells
• Complex cryptoglandular perianal fistula
• Efficacy
• Endorectal advancement flap
• Safety

• Adipose tissue
• Airway defects restoration
• Fistula
• Head and neck
• Lipotransfer
• Mesenchymal stromal cells
• Minimally invasive treatments
• Regenerative medicine
• Respiratory tract
• Tracheoesophageal fistula

• Adipose Tissue
• Humans
• Quality of Life
• Regenerative Medicine
• Respiratory Tract Fistula
• Stromal Cells
• Treatment Outcome

• Ministero della Salute

• COVID-19
• Case series
• Cellular therapy
• Mechanical ventilation
• Mesenchymal stromal cells
• Pneumonia
• SARS-CoV-2

The aim of this clinical trial (ID Number NCT01803347) was to determine the safety and efficacy of autologous adipose‐derived stem cells (ASCs) for treatment of cryptoglandular fistula. This research was conducted following an analysis of the mistakes of a same previous phase III clinical trial. We designed a multicenter, randomized, single‐blind clinical trial, recruiting 57 patients. Forty‐four patients were categorized as belonging to the intent‐to‐treat group. Of these, 23 patients received 100 million ASCs plus intralesional fibrin glue (group A) and 21 received intralesional fibrin glue (group B), both after a deeper curettage of tracks and closure of internal openings. Fistula healing was defined as complete re‐epithelialization of external openings. Those patients in whom the fistula had not healed after 16 weeks were eligible for retreatment. Patients were evaluated at 1, 4, 16, 36, and 52 weeks and 2 years after treatment. Results were assessed by an evaluator blinded to the type of treatment. After 16 weeks, the healing rate was 30.4% in group A and 42.8% in group B, rising to 55.0% and 63.1%, respectively, at 52 weeks. At the end of the study (2 years after treatment), the healing rate remained at 50.0% in group A and had reduced to 26.3% in group B. The safety of the cellular treatment was confirmed and no impact on fecal continence was detected. The main conclusion was that autologous ASCs for the treatment of cryptoglandular perianal fistula is safe and can favor long‐term and sustained fistula healing.

• complex cryptoglandular fistula
• mesenchymal stem cells
• phase III