Bone marrow mesenchymal stem cell-derived extracellular vesicle infusion for amyotrophic lateral sclerosis.

In this pilot safety study, we hypothesized that a human bone marrow stem cell-derived extracellular vesicle (hBM-MSC EV) investigational product (IP) would be safe and exhibit potential efficacy in amyotrophic lateral sclerosis (ALS) patients. Ten ALS patients received two 10-ml intravenous infusions of the IP given 1 month apart and evaluated over 3 months. There were no serious adverse events or adverse events related to the IP and 30% of subjects' ALS functional rating scale-revised (ALSFRS-R) scores did not decline.

Perianal Fistulizing Crohn's Disease: Utilizing the TOpClass Classification in Clinical Practice to Provide Targeted Individualized Care.

Background & Aims: Perianal fistulation is a challenging phenotype of Crohn's disease, with significant impact on quality of life. Historically, fistulae have been classified anatomically in relation to the sphincter complex, and management guidelines have been generalized, with lack of attention to the clinical heterogenicity seen. The recent 'TOpClass classification system' for perianal fistulizing Crohn's disease (PFCD) addresses this issue, and classifies patients into defined groups, which provide a focus for fistula management that aligns with disease characteristics and patient goals.

A novel extracellular vesicle paradigm for the treatment of COVID-19 induced acute respiratory distress syndrome (ARDS).

Efficacy of mesenchymal stem cells (MSCs) for treatment of acute respiratory distress syndrome (ARDS) suggests bioactive bone marrow MSC extracellular vesicles (BM-MSC EVs) may be effective. A patient with severe COVID-19 associated ARDS who was presumed to expire was treated with a BM-MSC EV preparation (14 doses over two months) as a rescue treatment for refractory COVID ARDS. Near complete reversal of lung inflammation and fibrosis (per computed tomography), near complete restoration of mobility, hospital discharge (3 months) with resumption of normal activities of daily living (one year) and return to work occurred.

Stem Cells and Stem Cell-Derived Factors for the Treatment of Inflammatory Bowel Disease with a Particular Focus on Perianal Fistulizing Disease: A Minireview on Future Perspectives.

Inflammatory bowel disease remains a difficult disease to effectively treat, especially fistulizing Crohn's disease. Perianal fistulas in the setting of Crohn's disease remain an area of unmet need with significant morbidity in this patient population. Up to one third of Crohn's patients will have perianal fistulizing disease and current medical and surgical interventions are of limited efficacy.

Perianal Fistulizing Crohn's Disease-Associated Anorectal and Fistula Cancers: Systematic Review and Expert Consensus.

Background & Aims: Perianal fistulizing Crohn's disease (PFCD)-associated anorectal and fistula cancers are rare but often devastating diagnoses. However, given the low incidence and consequent lack of data and clinical trials in the field, there is little to no guidance on screening and management of these cancers. To inform clinical practice, we developed consensus guidelines on PFCD-associated anorectal and fistula cancers by multidisciplinary experts from the international TOpClass consortium.

Patient engagement and satisfaction with early phase cell therapy clinical trials at a tertiary inflammatory bowel disease center.

Several clinical trials are underway investigating cell and gene therapy, and while these trials are meant to significantly impact patient care, they rely on patient engagement and participation. Unfortunately, clinical trials generally require extensive commitment by subjects. While several studies are using validated surveys to measure patient-reported outcomes, there is a lack of characterization of the patient experience as a subject in these trials.

Safety of bone marrow derived mesenchymal stem cell extracellular vesicle injection for lumbar facet joint pain.

A 3-month pilot study to evaluate the safety of injecting a bone marrow-derived mesenchymal stem cell extracellular vesicle advanced investigational product (IP) into the lumbar facet joint space as a treatment for chronic low back pain. 20 healthy adults were treated with IP injections (0.5 ml/joint) and evaluated by three functional assessments 1, 3, 7, 14, 30, 60 and 90 days later.

Tofacitinib Is Associated With Increased Risk of Postoperative Venous Thromboembolism in Patients With Ulcerative Colitis.

Background: In 2019, the Food and Drug Administration issued a black box warning for increased risk of venous thromboembolism in patients with rheumatoid arthritis exposed to tofacitinib. There are limited data regarding postoperative venous thromboembolism risk in patients with ulcerative colitis exposed to tofacitinib.

Objective: To assess whether preoperative exposure to tofacitinib is associated with increased odds of postoperative venous thromboembolism.

The mode of delivery does not influence the occurrence of post-partum perianal disease flares in patients with inflammatory bowel disease.

Introduction: Perianal disease occurs in up to 34% of inflammatory bowel disease (IBD) patients. An estimated 25% of women will become pregnant after the initial diagnosis, thus introducing the dilemma of whether mode of delivery affects perianal disease. The aim of our study was to analyze whether a cesarean section (C-section) or vaginal delivery influence perianal involvement.

Treatment effect of ex vivo expanded allogeneic bone marrow-derived mesenchymal stem cells for the treatment of fistulizing Crohn's disease are durable at 12 months.

Background: Mesenchymal stem cells have been administered via direct injection to treat perianal Crohn's fistulizing disease. We herein sought to determine the safety and durability of treatment response to 12 months with 3 individual phase IB/IIA clinical trials of mesenchymal stem cells for refractory perianal, rectovaginal, and ileal pouch fistulas in the setting of Crohn disease.

Methods: Three phase IB/IIA randomized placebo-controlled single-blinded clinical trials were performed for (1) perianal fistulas, (2) rectovaginal fistula, and (3) ileal pouch in situ with anovaginal and/or perianal fistulas.

Surgical Options for the Treatment of Perianal and Anovaginal Fistulas in the Setting of Ileoanal Pouch Crohn's Disease: Experience of a Tertiary Center.

Background: The leading cause of pouch failure following ileal pouch-anal anastomosis are peri-pouch fistulas and pelvic sepsis.

Objective: Determine the overall efficacy of current surgical therapy for the treatment of perianal and anovaginal fistulizing disease related to Crohn's disease phenotype of the pouch.

Design: Retrospective cohort study of a prospectively maintained, IRB-approved database.

Safety and Efficacy of Intravenous ExoFlo in the Treatment of Complex Regional Pain Syndrome.

Background: Complex regional pain syndrome (CRPS) is an extremely painful disorder driven primarily by inflammation.

Objectives: We hypothesized that the immunomodulatory biologic, ExoFloTM, composed of bone marrow mesenchymal stem cell-derived extracellular vesicles, could be safely administered to CRPS patients and alleviate symptoms.

Study Design: Ten patients received 2 intravenous (IV) infusions, each containing 15 mL ExoFlo, on day one and day 4.

A phase IB/IIA study of ex vivo expanded allogeneic bone marrow-derived mesenchymal stem cells for the treatment of rectovaginal fistulizing Crohn's disease.

Background: Crohn-related rectovaginal fistulas are notoriously difficult to treat. Studies of mesenchymal stem cells for the treatment of perianal Crohn fistulizing disease have largely excluded rectovaginal fistulas. The aim of this study was to determine the safety and efficacy of mesenchymal stem cells for refractory rectovaginal fistulizing Crohn disease.