title: A Refractory Celiac Patient Successfully Treated With Mesenchymal Stem Cell Infusions.
abstract: Type II refractory celiac disease (RCD), as defined according to the amount of aberrant intraepithelial lymphocytes, is a condition characterized by severe malabsorption syndrome and poor prognosis, with no effective treatment. Based on the regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs), we investigated the feasibility, safety, and efficacy of serial infusions of autologous bone marrow-derived MSCs in a 51-year-old woman with type II RCD. Mesenchymal stem cells were isolated, expanded, and characterized following standard protocols. Monitoring of the patient's malabsorption indexes, mucosal architecture, and percentage of aberrant intraepithelial lymphocytes was scheduled for the time of enrollment, at each infusion, and after 6 months. Determination of mucosal expression of interleukin (IL)-15 and its receptor was also performed. Expansion of MSCs was feasible, and the patient underwent 4 systemic infusions of 2 × 10(6) MSCs/kg body weight 4 months apart, without adverse effects. During the treatment period, she experienced gradual and durable amelioration of her general condition, with normalization of stool frequency, body mass index, laboratory test results, and mucosal architecture. Remarkably, the expression of IL-15 and its receptor almost completely disappeared. Thus, treatment of RCD with serial MSC infusions seems promising, leading to recovery from the life-threatening condition while blocking the IL-15 pathogenic pathway.
authors.affiliation: Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, Pavia, Italy. Electronic address: rachele.ciccocioppo@unipv.it.
authors.forename: Rachele
authors.initials: R
authors.lastname: Ciccocioppo
authors.affiliation: Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gallia
authors.affiliation: Cell Factory and Research Laboratory-Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Avanzini
authors.affiliation: Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Betti
authors.affiliation: Clinic Cytometry Laboratory-Department of Hematology, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Picone
authors.affiliation: Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vanoli
authors.affiliation: Department of Molecular Medicine, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Paganini
authors.affiliation: Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Biagi
authors.affiliation: Cell Factory and Research Laboratory-Department of Pediatrics, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Maccario
authors.affiliation: Department of Internal Medicine, Fondazione IRCCS Policlinico San Matteo and Università degli Studi di Pavia, Pavia, Italy.
authors.forename: Gino R
authors.initials: GR
authors.lastname: Corazza
mesh_terms: D015153:Blotting, Western / Q000379:methods; D002446:Celiac Disease / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006801:Humans; D019409:Interleukin-15 / Q000032:analysis; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D009092:Mucous Membrane / Q000166:cytology; D010288:Parenteral Nutrition / Q000379:methods*
chemical_list: D019409:Interleukin-15