Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis

Gabriela Constantin, Silvia Marconi, Barbara Rossi, Stefano Angiari, Laura Calderan, Elena Anghileri, Beatrice Gini, Simone Dorothea Bach, Marianna Martinello, Francesco Bifari, Mirco Galiè, Ermanna Turano, Simona Budui, Andrea Sbarbati, Mauro Krampera, Bruno Bonetti

Research output: Contribution to journalArticle

267 Citations (Scopus)

Abstract

Mesenchymal stem cells (MSCs) represent a promising therapeutic approach for neurological autoimmune diseases; previous studies have shown that treatment with bone marrow-derived MSCs induces immune modulation and reduces disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Here we show that intravenous administration of adipose-derived MSCs (ASCs) before disease onset significantly reduces the severity of EAE by immune modulation and decreases spinal cord inflammation and demyelination. ASCs preferentially home into lymphoid organs but also migrates inside the central nervous system (CNS). Most importantly, administration of ASCs in chronic established EAE significantly ameliorates the disease course and reduces both demyelination and axonal loss, and induces a Th2-type cytokine shift in T cells. Interestingly, a relevant subset of ASCs expresses activated α4 integrins and adheres to inflamed brain venules in intravital microscopy experiments. Bioluminescence imaging shows that α4 integrins control ASC accumulation in inflamed CNS. Importantly, we found that ASC cultures produce basic fibroblast growth factor, brain-derived growth factor, and platelet-derived growth factor-AB. Moreover, ASC infiltration within demyelinated areas is accompanied by increased number of endogenous oligodendrocyte progenitors. In conclusion, we show that ASCs have clear therapeutic potential by a bimodal mechanism, by suppressing the autoimmune response in early phases of disease as well as by inducing local neuroregeneration by endogenous progenitors in animals with established disease. Overall, our data suggest that ASCs represent a valuable tool for stem cell-based therapy in chronic inflammatory diseases of the CNS.

Original languageEnglish
Pages (from-to)2624-2635
Number of pages12
JournalStem Cells
Volume27
Issue number10
DOIs
Publication statusPublished - Oct 2009

Fingerprint

Autoimmune Experimental Encephalomyelitis
Mesenchymal Stromal Cells
Central Nervous System
Demyelinating Diseases
Integrins
Myelitis
Venules
Oligodendroglia
Fibroblast Growth Factor 2
Cell- and Tissue-Based Therapy
Autoimmunity
Intravenous Administration
Autoimmune Diseases
Multiple Sclerosis
Chronic Disease
Stem Cells
Therapeutics
Animal Models
Bone Marrow
Cytokines

Keywords

  • Adipose-derived mesenchymal stem cells
  • Chronic experimental autoimmune encephalomyelitis
  • Growth factors
  • Imaging, in vivo
  • Immune regulation
  • Neural precursors
  • T lymphocytes

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Constantin, G., Marconi, S., Rossi, B., Angiari, S., Calderan, L., Anghileri, E., ... Bonetti, B. (2009). Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells, 27(10), 2624-2635. https://doi.org/10.1002/stem.194

Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. / Constantin, Gabriela; Marconi, Silvia; Rossi, Barbara; Angiari, Stefano; Calderan, Laura; Anghileri, Elena; Gini, Beatrice; Bach, Simone Dorothea; Martinello, Marianna; Bifari, Francesco; Galiè, Mirco; Turano, Ermanna; Budui, Simona; Sbarbati, Andrea; Krampera, Mauro; Bonetti, Bruno.

In: Stem Cells, Vol. 27, No. 10, 10.2009, p. 2624-2635.

Research output: Contribution to journalArticle

Constantin, G, Marconi, S, Rossi, B, Angiari, S, Calderan, L, Anghileri, E, Gini, B, Bach, SD, Martinello, M, Bifari, F, Galiè, M, Turano, E, Budui, S, Sbarbati, A, Krampera, M & Bonetti, B 2009, 'Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis', Stem Cells, vol. 27, no. 10, pp. 2624-2635. https://doi.org/10.1002/stem.194
Constantin, Gabriela ; Marconi, Silvia ; Rossi, Barbara ; Angiari, Stefano ; Calderan, Laura ; Anghileri, Elena ; Gini, Beatrice ; Bach, Simone Dorothea ; Martinello, Marianna ; Bifari, Francesco ; Galiè, Mirco ; Turano, Ermanna ; Budui, Simona ; Sbarbati, Andrea ; Krampera, Mauro ; Bonetti, Bruno. / Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. In: Stem Cells. 2009 ; Vol. 27, No. 10. pp. 2624-2635.
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