• Humans
• Crohn Disease/complications
• Crohn Disease/therapy
• Rectal Fistula/therapy
• Rectal Fistula/etiology
• Male
• Female
• Retrospective Studies
• Adult
• Mesenchymal Stem Cell Transplantation/methods
• Middle Aged
• Spain
• Treatment Outcome

• Crohn's disease
• Human amnion epithelial cells
• Perianal fistula
• Stem cells

• Adult
• Humans
• Amnion
• Crohn Disease/complications
• Crohn Disease/diagnosis
• Crohn Disease/therapy
• Epithelial Cells
• Follow-Up Studies
• Hematopoietic Stem Cell Transplantation
• Mesenchymal Stem Cell Transplantation/adverse effects
• Mesenchymal Stem Cell Transplantation/methods
• Quality of Life
• Rectal Fistula/therapy
• Rectal Fistula/drug therapy
• Treatment Outcome

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

• Crohn’s disease
• Perianal fistula
• adipose-derived stem cells
• cell therapy
• darvadstrocel

• Humans
• Treatment Outcome
• Rectal Fistula/therapy
• Mesenchymal Stem Cells
• Crohn Disease/therapy
• Mesenchymal Stem Cell Transplantation

• Humans
• Crohn Disease/therapy
• Mesenchymal Stem Cells
• Treatment Outcome
• Mesenchymal Stem Cell Transplantation

• Cryptoglandular
• Perianal fistula
• Platelet concentrates
• Stromal cells
• Surgery

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.

• Crohn’s disease
• Extracellular vesicles
• Gastrointestinal fistulae
• Post-surgical fistulae
• Stem/stromal cells

• Animals
• Crohn Disease/pathology
• Crohn Disease/therapy
• Digestive System Fistula/pathology
• Digestive System Fistula/surgery
• Digestive System Fistula/therapy
• Extracellular Vesicles/metabolism
• Humans
• Mesenchymal Stem Cells/metabolism
• Regenerative Medicine/methods
• Stromal Cells/metabolism

Perianal fistula in patients with Crohn’s disease is an extremely challenging condition. The disease tends to reoccur, and with current treatment options, a large number of patients are left with active ailment and experience major morbidity. In recent years, hopeful results regarding local use of mesenchymal stem cells (MSCs) in perianal Crohn’s disease have been published. Although to this day there are no clear guidelines determining optimal dosage, injections frequency and culture conditions, their efficiency has proven to be much higher than conventionally used methods. According to studies, they can effectively induce as well as maintain fistula closure. This approach also avoids common side effects related to conventional surgical treatment.

• Crohn’s disease
• mesenchymal stem cells
• perianal Crohn’s disease
• perianal fistula

• Crohn disease
• fistulizing CD
• mesenchymal stromal cells
• perianal fistula
• stem cells
• surgical treatment

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

Inflammatory bowel disease (IBD), consisting primarily of ulcerative colitis and Crohn’s disease, is a group of debilitating auto-immune disorders, which also increases the risk of colitis-associated cancer. However, due to the chronic nature of the disease and inconsistent treatment outcomes of current anti-IBD drugs (e.g., approximately 30% non-responders to anti-TNFα agents), and related serious side effects, about half of all IBD patients (in millions) turn to alternative treatment options. In this regard, mucosal healing is gaining acceptance as a measure of disease activity in IBD patients as recent studies have correlated the success of mucosal healing with improved prognosis. However, despite the increasing clinical realization of the significance of the concept of mucosal healing, its regulation and means of therapeutic targeting remain largely unclear. Here, stem-cell therapy, which uses hematopoietic stem cells or mesenchymal stem cells, remains a promising option. Stem cells are the pluripotent cells with ability to differentiate into the epithelial and/or immune-modulatory cells. The over-reaching concept is that the stem cells can migrate to the damaged areas of the intestine to provide curative help in the mucosal healing process. Moreover, by differentiating into the mature intestinal epithelial cells, the stem cells also help in restoring the barrier integrity of the intestinal lining and hence prevent the immunomodulatory induction, the root cause of the IBD. In this article, we elaborate upon the current status of the clinical management of IBD and potential role of the stem cell therapy in improving IBD therapy and patient’s quality of life.

• Crohn′s disease
• Ulcerative colitis
• Mesenchymal stem cells
• Hematopoietic stem cells
• Mucosal healing

• I01 BX002086 BLRD VA
• I01 BX002761 BLRD VA
• R01 DK124095 NIDDK NIH HHS
• R21 CA216746 NCI NIH HHS

Objective: To evaluate the short term safety and potential therapeutic effect of allogenic adipose tissue-derived stromal/stem cells (ASCs) + cholecalciferol in patients with recent-onset T1D.

Methods: Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1 × 10⁶ cells/kg) and cholecalciferol 2000 UI/day for 3 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide (CP), insulin dose, HbA1c, time in range (TIR), glucose variability (continuous glucose monitoring) and frequency of CD4⁺FoxP3+ T-cells (flow cytometry) were evaluated at baseline (T0) and after 3 months (T3).

Results: 13 patients were included (8: group 1; 5: group 2). Their mean age and disease duration were 26.7 ± 6.1 years and 2.9 ± 1.05 months. Adverse events were transient headache (n = 8), mild local reactions (n = 7), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), mild floaters (n = 2), central retinal vein occlusion (n = 1, complete resolution). At T3, group 1 had lower insulin requirement (0.22 ± 0.17 vs. 0.61±0.26IU/Kg; p = 0.01) and HbA1c (6.47 ± 0.86 vs. 7.48 ± 0.52%; p = 0.03) than group 2. In group 1, 2 patients became insulin free (for 4 and 8 weeks) and all were in honeymoon at T3 (vs. none in group 2; p = 0.01). CP variations did not differ between groups (−4.6 ± 29.1% vs. +2.3 ± 59.65%; p = 0.83).

Conclusions: Allogenic ASCs + cholecalciferol without immunosuppression was associated with stability of CP and unanticipated mild transient adverse events in patients with recent onset T1D.

ClinicalTrials.gov registration: NCT03920397.

• adipose tissue-derived stromal/stem cells
• pancreatic function
• transplant
• type 1 diabetes
• vitamin D

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

Crohn’s disease is a pathological condition that has different options of treatment, but there are patients who need other therapeutic approach, such as the use of adipose-derived mesenchymal stem cells.

Systematic literature review to determine the different ways of adipose-derived mesenchymal stem cells administration in humans with luminal refractory and perianal fistulizing Crohn’s disease.

It was conducted a search for articles (from 2008 to 2018) on PubMed and ScienceDirect databases using the keywords Crohn’s disease, fistulizing Crohn’s disease, luminal Crohn’s disease and transplantation of mesenchymal stem cells or mesenchymal stem cells or stromal cells. Thirteen publications were selected for analysis.

Only one study referred to the luminal Crohn´s disease. The number of cells administered was variable, occurring mainly through subcutaneous adipose tissue by liposuction. It could be highlighted the autologous transplant with exclusive infusion of mesenchymal stem cells. The procedures involved in pre-transplant were mainly curettage, setons placement and stitching with absorbable suture, and conducting tests and drug treatment for luminal Crohn´s disease. During transplant, the injection of mesenchymal stem cells across the fistula path during the transplant was mainly on the intestinal tract wall.

Although the use of mesenchymal stem cells is promising, the transplant on the luminal region should be more investigated. The injection of mesenchymal stem cells, exclusively, is more explored when compared to treatment with other products. The preparation of the fistulizing tract and the location of cell transplantation involve standardized health care in most studies.

• Fistula-in-ano
• Mesenchymal stroma cells
• Perianal fistula
• Platelet-rich plasma

Perianal fistulizing Crohn’s disease (PFCD) is associated with significant morbidity and might negatively impact the quality of life of CD patients. In the last two decades, the management of PFCD has evolved in terms of the multidisciplinary approach involving gastroenterologists and colorectal surgeons. However, the highest fistula healing rates, even combining surgical and anti-TNF agents, reaches 50% of treated patients. More recently, the administration of mesenchymal stem cells (MSCs) have shown notable promising results in the treatment of PFCD. The aim of this review is to describe the rationale and the possible mechanism of action of MSC application for PFCD and the most recent results of randomized clinical trials. Furthermore, the unmet needs of the current administration process and the expected next steps to improve the outcomes will be addressed.

• Crohn’s disease
• fistula
• perianal
• stem cells

• Animals
• Crohn Disease/therapy
• Humans
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells/cytology
• Mice
• Quality of Life
• Randomized Controlled Trials as Topic
• Rectal Fistula/pathology
• Rectal Fistula/therapy
• Wound Healing

To report our experience in a compassionate use program for complex perianal fistula.

Under controlled circumstances and approved by European and Spanish laws, a compassionate use program allows the use of stem cell therapy for patients with nonhealing diseases, mostly complex fistula-in-ano, who do not meet criteria to be included in a clinical trial. Candidates had previously undergone multiple surgical interventions that had failed. The intervention consisted of surgery (with closure of the internal opening or a surgical flap performance), followed by stem cell injection. Three types of cells were used for implant: stromal vascular fraction, autologous expanded adipose-derived, or allogenic adipose-derived stem cells. Healing was evaluated at 6^th month follow-up. Outcome was classified as partial response or healing. Relapse was evaluated 1 year later. Maximum follow-up period was 48 months.

45 patients (24 male) were included; the mean age was 45 years, which ranged from 24 to 69 years. Since some of them received repeated doses, 52 cases were considered (42 fistula-in-ano, 7 rectovaginal fistulas, 1 urethrorectal fistula, 1 sacral fistula, and 1 hidradenitis suppurativa). Regarding fistula-in-ano, there were 18 Crohn's-associated and 24 cryptoglandular. 49 cases (94.2%) showed partial response starting 6.5 weeks of follow-up. 24 cases (46.2%) healed in a mean time of 5.5 months. A year later, all patients cured remained healed. No adverse effects related to stem cell therapy were reported.

Stem cells are safe and useful for treating anal fistulae. Healing can be achieved in severe cases.