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Abstract Defects in ataxin-3 proteins and CAG repeat expansions in its coding gene ATXN3 cause Spinocerebellar Ataxia Type 3 (SCA3) or Machado-Joseph disease (MJD) polyglutamine neurodegenerative disease. The mutant proteins aggregate as inclusion bodies in cells and compete with wild-type ataxin-3, which leads to neuronal dysfunction or death and impairs Beclin1-mediated autophagy. It has been reported that Mesenchymal stem cells (MSCs) can reliably treat several neurodegenerative diseases. Herein, we used a Transcription Factor EB (TFEB) nuclear translocation-mediated MSCs co-culture approach to reconstitute autophagy and lysosomal biogenesis, and reduce SCA3-like behaviors in induced pluripotent stem cells (iPSCs)-derived neuron cells models. Our iPSCs model showed enhanced expression of autophagy proteins, attenuated the expression and toxic effects of mutant ataxin-3 on neurons, and alleviated the effects of ataxin-3 on autophagy. Therefore, MSCs are associated with autophagy-inducing therapy and compared to animal models, our MSCs co-culture could be used as a novel and potential therapeutic approach to study SCA3 disease and other neurodegenerative diseases.

Abstract 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. We hypothesized the delivery route would not alter post-partum perianal manifestations in the setting of previously healed perianal disease. Methods All consecutive eligible IBD female patients between 1997 and 2022 who delivered were included. Prior perianal involvement, perianal flare after delivery and delivery method were noted. Results We identified 190 patients with IBD who had a total of 322 deliveries; 169 (52%) were vaginal and 153 (48%) were by C-section. Nineteen women (10%) experienced 21/322 (6%) post-partum perianal flares. Independent predictors were previous abdominal surgery for IBD (OR, 2.7; 95% CI, 1–7.2; p = 0.042), ileocolonic involvement (OR, 3.3; 95% CI, 1.1–9.4; p = 0.030), previous perianal disease (OR, 22; 95% CI, 7–69; p

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. No adverse events occurred despite repeated dosing of investigational product, highlighting safety of this potential therapy for ARDS.

Abstract Background Mesenchymal stem cells (MSCs) are a well-established immunomodulatory agent which can also promote tissue repair and regeneration. Recent studies have demonstrated MSCs as a novel therapeutic for inflammatory bowel disease (IBD), a chronic idiopathic inflammatory disorder of the gastrointestinal tract. However, the precise role of MSCs in regulating immune responses is controversial, and its significance in the pathogenesis remains IBD undefined. In addition, MSCs’ acellular product, extracellular vesicles (EVs), may also play an important role in the armamentarium of therapeutics, but how EVs compare to MSCs remains unknown due to the lack of side-by-side comparative investigation. We herein compared MSCs and MSC-derived EVs for the treatment of IBD using a DSS-induced colitis model. Methods A DSS-induced colitis model was used. At day 4, mice received adipose-derived MSCs, MSC-derived EVs, or placebo. Weight loss, stool consistency, and hematochezia was charted. At day 8, murine colons were harvested, histologic analysis performed, and serum/tissue cytokine analysis conducted. Results MSCs and EVs demonstrated equivalent immunosuppressive function in DSS-treated mice through decreased colonic lymphocyte infiltration and attenuated disease severity after both MSC and EV treatment. Furthermore, both MSCs and EVs have an equivalent ability to inhibit inflammation in the DSS colitis model by inhibiting JAK, JNK 1/2, and STAT3 signaling. Conclusions These results suggest that (i) both MSCs and EVs are effective therapeutic candidates for a DSS-induced mouse colitis model, (ii) MSCs and EVs have similar immunosuppressive and anti-inflammatory functions, and (iii) EVs may present a novel future therapeutic for the treatment of IBD.

Abstract Background Precision or individualized medicine is increasingly pervasive across medical and surgical disciplines. However, the concept has not been introduced in regenerative medicine. Main body Targeted and engineered cellular and acellular therapy, specific to individuals or disease states, could significantly improve the efficacy of these autologous therapies. Currently, generic mesenchymal stem cell therapy is being widely used across multiple pathologies, some of which may not respond well to mesenchymal stem cell therapy. Engineered cell therapy may be a way to address this generic one-size-fits-all approach. Conclusions The future of regenerative medicine lies in the concept of precision cell-based therapy.

Background: Vedolizumab (VDZ) is a gut-specific α4-β7 integrin antagonist that has demonstrated efficacy in Crohn’s disease (CD) and ulcerative colitis (UC). The safety of VDZ in the perioperative period remains unclear. The aim of this study was to evaluate postoperative complications and perioperative safety in VDZ-treated patients undergoing nonintestinal operations. Methods: A case-matched study was performed at two inflammatory bowel disease (IBD) referral centers. Adult patients with CD and UC who underwent a nonintestinal surgical procedure during treatment with VDZ were included. Patients who had their last VDZ infusion up to 12 weeks before the procedure were considered exposed and were matched in a 1:1 ratio to patients without VDZ therapy, according to type of surgical procedure, age, and sex. The primary outcome was overall risk of early postoperative infectious complications (up to 30 days after surgery), readmissions, reoperations, surgical site infections, and other infections. The VDZ and control groups were subsequently compared using the Pearson χ 2 test and Wilcoxon rank sum. Results: We identified 34 patients treated with VDZ who underwent 36 nonintestinal surgical procedures. These patients were matched with 36 control procedures. Postoperative complications were not different between the VDZ-treated and control cohorts for all outcomes analyzed: infectious complications occurred in 14% versus 8% ( p = 0.45), superficial surgical site infections 6% versus 0% ( p = 0.15), reoperations 6% versus 3% ( p = 0.56) and readmissions 11% versus 6% ( p = 0.37). Conclusions: VDZ-treated patients with IBD undergoing nonintestinal procedures did not have an increased risk of overall postoperative infections or other complications compared with matched controls.

An Ehrlichia muris–like (EML) pathogen was detected among 4 patients in Minnesota and Wisconsin during 2009. We characterized additional cases clinically and epidemiologically. During 2004–2013, blood samples from 75,077 patients from all 50 United States were tested by PCR from the groEL gene for Ehrlichia spp. and Anaplasma phagocytophilum. During 2007–2013, samples from 69 (0.1%) patients were positive for the EML pathogen; patients were from 5 states: Indiana (1), Michigan (1), Minnesota (33), North Dakota (3), and Wisconsin (31). Most (64%) patients were male; median age was 63 (range 15–94) years; and all 69 patients reported likely tick exposure in Minnesota or Wisconsin. Fever, malaise, thrombocytopenia, and lymphopenia were the most common symptoms. Sixteen (23%) patients were hospitalized (median 4 days); all recovered, and 96% received doxycycline. Infection with the EML pathogen should be considered for persons reporting tick exposure in Minnesota or Wisconsin.