Mesenchymal properties of SJL mice-stem cells and their efficacy as autologous therapy in a relapsing–remitting multiple sclerosis model

Abstract

IntroductionMesenchymal stem cells (MSCs) are a multipotent population of adult stem cells, which may represent a promising therapeutic approach for neurological autoimmune diseases such as multiple sclerosis. The mouse is the most used species for obtaining and studying the characteristics of MSC and their potential as autologous transplants in pre-clinical models. However, conflicting data have been published disclosing intraspecies variations. The choice of the mouse strain and the tissue source appear, among others, as important factors in the experimental application of MSCs.MethodsAdipose tissue-derived MSCs obtained from the SJL/JCrl mouse strain (SJL-AdMSC) have been cultured for a long time (from passage 0 up to 15) under controlled experimental conditions, and their growth rate, morphology, stromal and haematopoietic marker expression profiles and differentiation capacity towards adipocytes, osteocytes and chondrocytes have been determined. Moreover, their preclinical efficacy has been assessed by autologous transplant in relapsing-remitting experimental autoimmune encephalomielitis (RR-EAE)-induced SJL mice (a well established mice model for the study of RR-multiple sclerosis).ResultsWe demonstrate that SJL-AdMSCs show the same fibroblastic shape, growth rate, profile of markers expression and multipotency described for MSCs in every passage evaluated (up to passage 15). Additionally, SJL-AdMSCs ameliorate the RR-EAE course, suggesting that they could modulate disease progression. Moreover, their features studied are fully comparable with the standardized Ad-MSCs obtained from the C57BL/6 mouse strain, which strengthens their use in cell therapy.ConclusionSJL-AdMSCs might be a suitable source of Ad-MSCs for studies related to the properties of MSCs and their application as promising therapeutic tools in autologous transplants in experimental medicine.

Gene therapy with mesenchymal stem cells expressing IFN‐ß ameliorates neuroinflammation in experimental models of multiple sclerosis

“…After the mice had been killed by cervical dislocation, adipose tissue fragments were obtained from s.c. abdominal fat. The isolation, culture and expansion of murine AdMSCs were performed as described previously (Marin‐Bańasco et al , ). Cells were resuspended in Complete MesenCult® Medium (STEMCELLS Technologies, Grenoble, France), supplemented with streptomycin and penicillin (PAA Laboratories GmbH, Pasching, Austria) seeded in six‐well culture plates (1 × 10 6 cells per 9.6 cm 2 dish) and, thereafter, expanded with the aforementioned medium from 1 up to 10 passages (p).…”

“…The rationale for their use in MS was originally based on their differentiation and immunoregulatory capacities (Dominici et al , ; Tyndall et al , ; Constantin et al , ; Ben‐Ami et al , ; Mizuno et al , ). In mice with experimental autoimmune encephalomyelitis (EAE), the animal model most frequently used for MS that mimics the T‐cell‐mediated demyelination that occurs in the CNS (Friese et al , ; Steinman and Zamvil, ; Moreno et al , ), the transplant of MSCs ameliorates the clinical symptoms, the infiltration of inflammatory cells into the CNS, demyelination and axonal damage (Uccelli et al , ; Constantin et al , ; Newman et al , ; Freedman et al , ; Marin‐Bańasco et al , ). Their potential mechanisms include the suppression of both innate and adaptive immune cells and the up‐regulation of the generation of regulatory T‐cells (Uccelli et al , ; Newman et al , ; Cohen, ).…”

“…In this study, we have genetically manipulated our previously characterized murine adipose‐derived MSCs (AdMSCs) (Marin‐Bańasco et al , ) to constitutively produce IFN‐ß (AdMSCs‐IFN‐ß), in order to use them as autologous and allogeneic gene therapy in models of both relapsing–remitting EAE (RR‐EAE)and chronic progressive EAE (CP‐EAE).…”

The transplantation of mesenchymal stem cells derived from unconventional sources: an innovative approach to multiple sclerosis therapy

“…Several studies performed using AD-MSCs in EAE model established that AD-MSCs-based cell therapy is able to ameliorate disease development and enhance antiinflammatory responses (Marin-Banasco et al 2014;Semon et al 2014). In study by Yousefi et al (2013), the therapeutic efficacy of intraperitoneal and intravenous transplantation of allogenic AD-MSCs (1 × 10 6 ) was compared in EAE mice.…”

“…In study by Marin-Banasco et al (2014), the efficacy of ADMSCs has been assessed by autologous transplantation in relapsing-remitting EAE (RR-EAE)-induced SJL mice.…”