Case reportMesenchymal Stromal Cell Infusions as Rescue Therapy for Corticosteroid-Refractory Adult Autoimmune Enteropathy
Section snippets
Case Report
In March 2009, a 61-year-old woman was hospitalized for severe malabsorption syndrome due to chronic diarrhea lasting 2 years. Findings from stool examinations for occult blood and pathogens were negative; findings from lower endoscopy were unremarkable, whereas upper endoscopy with biopsy showed villous atrophy and inflammatory infiltrate of the duodenal mucosa. Although the results of serologic screening for celiac disease (the search for antiendomysium and anti–tissue transglutaminase
Patient Outcome
No adverse event was recorded during MSC infusion or in the following 22 months. A few days after the second infusion, the patient experienced a dramatic amelioration of her clinical condition and regularization of stool frequency, permitting her hospital discharge within 1 week. One month later, enterocyte autoantibodies were no longer detectable, and patchy recovery of duodenal mucosa at endoscopic and histologic examination was clearly evident (Figure 1, B), together with normalization of
Discussion
In the past decade, MSCs have been proposed and used as a new therapeutic strategy in immune-mediated disorders.13 Regarding chronic inflammatory bowel disease, we have already successfully treated fistulizing Crohn disease refractory to conventional treatments with local injections of autologous bone marrow–derived MSCs.14 After a benefit was observed in a mouse model of multiorgan autoimmunity,6 we used MSC infusions as described herein as rescue therapy in a patient with life-threatening
Conclusion
These data suggest that MSC infusions are safe and useful in the short term for treating AIE, mainly when refractory to current therapies. The increase in regulatory T-cell and plasma cell numbers in the gut mucosa may play a role in silencing the pathogenic pathways leading to autoantibody production and tissue injury. However, further in vivo studies are needed to explain the lack of long-lasting benefits and to define the optimal conditions for the use of MSCs as immunotherapy.
Acknowledgments
We thank Dr Paola Bianchi for detection of antienterocyte antibody, Dr Sergio Rutella for critical reading of the manuscript, and Mrs Susan West for careful revision of the English language.
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2021, Cell Stem CellCitation Excerpt :Through similar paracrine mechanisms, MSCs exert significant immunoregulatory functions that are capable of influencing both adaptive and innate immune responses once MSCs are activated by the inflammatory microenvironment (Krampera, 2011). MSC-mediated immunoregulation has been confirmed by preclinical and clinical studies based on systemic or local MSC administration in a broad spectrum of inflammatory and autoimmune diseases, such as graft-versus-host disease (GvHD) (Le Blanc et al., 2008), Crohn’s disease and fistulising or ulcerative enteropathies (Garcia-Olmo et al., 2009; Ciccocioppo et al., 2012; Ciccocioppo and Corazza, 2016), as well as cardiovascular diseases (Patel and Genovese, 2011; Toma et al., 2011), acute kidney damage (Tögel et al., 2005), colitis and sepsis (Gonzalez-Rey et al., 2009), and other diseases. Similar results in favor of the therapeutic efficacy of autologous or allogeneic MSC infusion were obtained in solid organ transplantation, reducing the need for concomitant immunosuppression (Podestà et al., 2019).
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2019, CytotherapyCitation Excerpt :In other words, we need to figure out what would be a biologically sound interval among the infusions on the basis of the half-life of the MSC effects rather than that of MSCs themselves. In this regard, we would mention the experience collected from treating a woman with life-threatening malabsorption syndrome due to adult autoimmune enteropathy with two intravenous infusions of autologous bone marrow–derived MSCs 2 weeks apart [107]. Although the therapy led to disappearance of the specific anti-enterocyte autoantibodies and to growth of intestinal villi, thus allowing the patient to overcome the critical stage, the benefit lasted only 3 months.
Adipose mesenchymal stromal cells: Definition, immunomodulatory properties, mechanical isolation and interest for plastic surgery
2019, Annales de Chirurgie Plastique EsthetiqueCitation Excerpt :Lymphocytes are the leucocytes implicated in adaptive immune response, and two main lines may be distinguished: T and B. With regard to T lymphocytes, MSCs inhibit proliferation [45,46], cytotoxicity and IFN-γ production [45,46]. MSCs induce differentiation into regulatory T lymphocyte (Treg)CD4posCD25highFOXP3pos [47–51]. MSCs can also impact secretory profile and, consequently, lymphocyte function.
Grant Support: This study was supported in part by grants from Fondazione Celiachia Italia (“Studio di possibili fattori ambientali e sviluppo di nuove strategie terapeutiche nelle complicanze della malattia celiaca”) (G.R.C); Ministero dell'Istruzione, dell'Università e della Ricerca, Progetti di Rilevante Interesse Nazionale; Associazione Italiana per la Ricerca sul Cancro; Ospedale Pediatrico Bambino Gesù, Roma; and the Associazione Italiana per la Ricerca sul Cancro special project “5 per mille” (F.L.).