Library - Ulcerative colitis
Stem Cell Res Ther. 2015 Sep 9;6:170. doi: 10.1186/s13287-015-0166-2.
Human cord blood-derived platelet lysate enhances the therapeutic activity of adipose-derived mesenchymal stromal cells isolated from Crohn’s disease patients in a mouse model of colitis.
Forte D1, Ciciarello M2, Valerii MC3, De Fazio L4, Cavazza E5, Giordano R6, Parazzi V7, Lazzari L8, Laureti S9, Rizzello F10, Cavo M11, Curti A12, Lemoli RM13, Spisni E14, Catani L15.
1Institute of Hematology “L. & A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, Policlinico S. Orsola-Malpighi, University of Bologna, via G. Massarenti 9, 40138, Bologna, Italy. dorian.forte2@unibo.it.
2Institute of Hematology “L. & A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, Policlinico S. Orsola-Malpighi, University of Bologna, via G. Massarenti 9, 40138, Bologna, Italy. marilena.ciciarello2@unibo.it.
3Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126, Bologna, Italy. chiaravalerii@hotmail.it.
4Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126, Bologna, Italy. luigia.defazio2@unibo.it.
5Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126, Bologna, Italy. elena.cavazza@studio.unibo.it.
6Cell Factory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, via F. Sforza 35, 20122, Milano, Italy. rosaria.giordano@policlinico.mi.it.
7Cell Factory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, via F. Sforza 35, 20122, Milano, Italy. valentina.parazzi@gmail.com.
8Cell Factory, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, via F. Sforza 35, 20122, Milano, Italy. lorenza.lazzari@policlinico.mi.it.
9Inflammatory Bowel Disease Unit, Policlinico S. Orsola-Malpighi, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. silvio.laureti2@unibo.it.
10Inflammatory Bowel Disease Unit, Policlinico S. Orsola-Malpighi, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. fernando.rizzello@unibo.it.
11Institute of Hematology “L. & A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, Policlinico S. Orsola-Malpighi, University of Bologna, via G. Massarenti 9, 40138, Bologna, Italy. michele.cavo@unibo.it.
12Institute of Hematology “L. & A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, Policlinico S. Orsola-Malpighi, University of Bologna, via G. Massarenti 9, 40138, Bologna, Italy. antonio.curti2@unibo.it.
13Chair of Hematology, Department of Internal and Specialty Medicine (DiMI), University of Genoa, Viale Benedetto XV 6, 16132, Genoa, Italy. roberto.lemoli@unige.it.
14Department of Biological, Geological and Environmental Sciences, Biology Unit, University of Bologna, Via Selmi 3, 40126, Bologna, Italy. enzo.spisni@unibo.it.
15Institute of Hematology “L. & A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, Policlinico S. Orsola-Malpighi, University of Bologna, via G. Massarenti 9, 40138, Bologna, Italy. lucia.catani@unibo.it.
Abstract
INTRODUCTION:
Due to their immunomodulatory properties, mesenchymal stromal cells (MSCs) have been used for auto-immune disease treatment. Crohn disease (CD) and ulcerative colitis are two major inflammatory bowel diseases (IBDs), resulting from pathological immune responses to environmental or microbial antigens. Preclinical and clinical studies have suggested that MSC-based cellular therapy hold promising potential for IBD treatment. However, open issues include the selection of the proper cell dose, the source and the optimal route of administration of MSCs for more effective results. Platelet lysate has gained clinical interest due to its efficacy in accelerating wound healing. Thus, we propose to combine the administration of MSCs with a human umbilical cord blood-derived platelet lysate (hCBPL) as a novel strategy to improve MSC-based therapy for IBD resolution.
METHODS:
Colitis was induced in 8-week-old C57BL/6J mice by daily oral administration of dextran sulphate sodium (DSS) (1.5 % w/v in tap water) for 9 days. MSCs were isolated from adipose tissue of CD patients (adCD-MSCs), expanded in proliferation medium, resuspended in hCBPL or PBS and administrated via enema for three times (1 × 10(6) cells/mouse/time) every other day starting on day +7 from DSS induction. The colitis evolution was evaluated by daily monitoring of body weight, stool consistency and bleeding. Histopathological analysis was performed. Inflammatory cytokine plasma levels were determined. adCD-MSCs stained with lipophilic membrane dye Nile Red, were injected in DSS mice as described above. Colon section of mice sacrificed 24 hours after last cell administration, were analyzed by confocal microscopy.
RESULTS:
We found that adCD-MSCs could be easily isolated and expanded from CD patients. Upon injection, adCD-MSCs exerted a therapeutic effect on DSS-induced colitis. Moreover, hCBPL increased adCD-MSCs efficacy by significantly reducing colitis scores, extension of the colon inflamed area and plasma levels of inflammatory mediators. Finally, Nile Red staining of MSCs is very efficient, stable and does not impair their vitality and function. Nile Red-labelling was clearly detected in the colitic area of adCD-MSCs injected mice and it was significantly brighter in the colon sections of mice that had received adCD-MSCs/hCBPL.
CONCLUSIONS:
In summary, with this study we propose a novel and promising adCD-MSC/hCBPL-based therapy for refractory IBDs.
Vet J. 2015 Dec;206(3):385-90. doi: 10.1016/j.tvjl.2015.08.003. Epub 2015 Aug 7.
Safety and efficacy of allogeneic adipose tissue-derived mesenchymal stem cells for treatment of dogs with inflammatory bowel disease: Clinical and laboratory outcomes.
Pérez-Merino EM1, Usón-Casaús JM2, Zaragoza-Bayle C2, Duque-Carrasco J3, Mariñas-Pardo L4, Hermida-Prieto M4, Barrera-Chacón R2, Gualtieri M5.
1Department of Animal Medicine and Surgery, Veterinary Faculty, University of Extremadura, 10003 Cáceres, Spain. Electronic address: evama@unex.es.
2Department of Animal Medicine and Surgery, Veterinary Faculty, University of Extremadura, 10003 Cáceres, Spain.
3Veterinary Teaching Hospital, Veterinary Faculty, University of Extremadura, 10003 Cáceres, Spain.
4Centauri Biotech Company, 15142 Arteixo, A Coruña, Spain.
5Department of Health Animal Science and Food Safety, Section of Surgery, Veterinary Faculty, Via Celoria, 10. 20133 Milan, Italy.
Abstract
Mesenchymal stem cells (MSCs) have shown immunomodulatory and anti-inflammatory effects in experimental colitis, and promising clinical results have been obtained in humans with Crohn’s disease and ulcerative colitis. The aim of this study was to determine the safety and feasibility of adipose tissue-derived MSC (ASC) therapy in dogs with inflammatory bowel disease (IBD). Eleven dogs with confirmed IBD received one ASC intravascular (IV) infusion (2 × 10(6) cells/kg bodyweight). The outcome measures were clinical response based on percentage reduction of the validated Clinical Inflammatory Bowel Disease Activity Index (CIBDAI) and Canine Chronic Enteropathy Clinical Activity Index (CCECAI), as well as normalisation of C-reactive protein (CRP), albumin, folate and cobalamin serum concentrations at day 42 post-treatment. The Wilcoxon test was used to compare variables before and after treatment. No acute reaction to ASC infusion and no side effects were reported during follow-up in any dog. Six weeks post-treatment, the CIBDAI and CCECAI decreased significantly and albumin, cobalamin and folate concentrations increased substantially. Differences in CRP concentrations pre- and post-treatment were not significant (P = 0.050). Clinical remission (defined by a reduction of initial CIBDAI and CCECAI >75%) occurred in 9/11 dogs at day 42. The two remaining dogs showed a partial response with reduction percentages of 69.2% and 71.4%. In conclusion, a single IV infusion of allogeneic ASCs was well tolerated and appeared to produce clinical benefits in dogs with severe IBD.
KEYWORDS: Albumin; Canine; Clinical activity index; Inflammatory bowel disease; Mesenchymal stem cell; Treatment
World J Gastroenterol. 2014 Dec 28;20(48):18228-39. doi: 10.3748/wjg.v20.i48.18228.
Intravenous vs intraperitoneal mesenchymal stem cells administration: what is the best route for treating experimental colitis?
Gonçalves Fda C1, Schneider N1, Pinto FO1, Meyer FS1, Visioli F1, Pfaffenseller B1, Lopez PL1, Passos EP1, Cirne-Lima EO1, Meurer L1, Paz AH1.
1Fabiany da Costa Gonçalves, Natália Schneider, Fernanda Otesbelgue Pinto, Fabíola Schons Meyer, Bianca Pfaffenseller, Eduardo Pandolfi Passos, Elizabeth Obino Cirne-Lima, Ana Helena Paz, Centro de Pesquisa Experimental do Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Rio Grande do Sul, Brazil.
Abstract
AIM:
To investigate the therapeutic effects of mesenchymal stem cells (MSCs) transplanted intraperitoneally and intravenously in a murine model of colitis.
METHODS:
MSCs were isolated from C57BL/6 mouse adipose tissue. MSC cultures were analyzed according to morphology, cellular differentiation potential, and surface molecular markers. Experimental acute colitis was induced in C57BL/6 mice by oral administration of 2% dextran sulfate sodium (DSS) in drinking water ad libitum from days 0 to 7. Colitis mice were treated with 1 × 10(6) MSCs via intraperitoneal or intravenous injection on days 2 and 5. The disease activity index was determined daily based on the following parameters: weight loss, stool consistency and presence of blood in the feces and anus. To compare morphological and functional differences in tissue regeneration between different MSC injection modalities, mice were euthanized on day 8, and their colons were examined for length, weight, and histopathological changes. Inflammatory responses were determined by measuring the levels of different serum cytokines using a CBA Th1/Th2/Th17 kit. Apoptotic rates were evaluated by terminal deoxynucleotidyl transferase-mediated dUDP-biotin nick end labeling assay.
RESULTS:
Intravenous infusion of MSCs was more effective than intraperitoneal treatment (P < 0.001) in reducing the clinical and histopathologic severity of colitis, which includes weight loss, diarrhea and inflammation. An histological evaluation demonstrated decreased colonic inflammation based on reduced crypt loss and reduced infiltration of inflammatory cells. This therapeutic effect was most likely mediated by the down-regulation of pro-inflammatory cytokines [interleukin (IL)-6 and tumor necrosis factor (TNF)]; and by the up-regulation of anti-inflammatory cytokines (IL-10 and IL-4). Intravenous transplantation also induced high levels of IFN that lead to activation of the immunosuppressive activity of the MSCs, which did not occur with intraperitoneal transplantation (P = 0.006). An increase in apoptotic T cells was observed after intravenous, but not intraperitoneal, MSC infusion, suggesting that MSCs can induce apoptosis in resistant T cells in colonic inflammation (P = 0.027).
CONCLUSION:
Our results demonstrate that intravenous treatment is a superior method for reducing colon inflammation compared with intraperitoneal therapy.
KEYWORDS: Cell transplantation; Dextran sulfate sodium; Immunomodulation; Inflammatory bowel disease; Intravenous injection; Mesenchymal stem cell; Ulcerative colitis