Mesenchymal stem cells encapsulated into biomimetic hydrogel scaffold gradually release CCL2 chemokine in situ preserving cytoarchitecture and promoting functional recovery in spinal cord injury

JOURNAL OF CONTROLLED RELEASE

卷:278

Article

Papa, S.¹  Vismara, I¹  Mariani, A.²  Barilani, M.^3,4  Rimondo, S.⁵  De Paola, M.²  Panini, N.⁶  Erba, E.⁶  Mauri, E.⁵  Rossi, F.⁵  Forloni, G.¹  Lazzari, L.⁴  Veglianese, P.¹ 

[1] IRCCS Ist Ric Farmacol Mario Negri, Dept Neurosci, Via La Masa 19, I-20156 Milan, Italy

[2] IRCCS Ist Ric Farmacol Mario Negri, Dept Environm Hlth Sci, Via La Masa 19, I-20156 Milan, Italy

[3] Univ Milan, EPIGET LAB, Dept Clin Sci & Community Hlth, Milan, Italy

[4] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Unit Rigenerat Med Cell Factory, Milan, Italy

[5] Politecn Milan, Dept Chem Mat & Chem Engn Giulio Natta, Via Mancinelli 7, I-20131 Milan, Italy

[6] IRCCS Ist Ric Farmacol Mario Negri, Dept Oncol, Via La Masa 19, I-20156 Milan, Italy

关键词: Hydrogel;    Mesenchymal stem cells;    Spinal cord injury;    Human chemokine (C-C motif) ligand 2;    CCL2;    Microglia/macrophages;    Motor neurons;   

DOI  :  10.1016/j.jconrel.2018.03.034

来源: Elsevier

【 摘 要 】

Spinal cord injury (SCI) is an acute neurodegenerative disorder caused by traumatic damage of the spinal cord. The neuropathological evolution of the primary trauma involves multifactorial processes that exacerbate the pathology, worsening the neurodegeneration and limiting neuroregeneration. This complexity suggests that multi-therapeutic approaches, rather than any single treatment, might be more effective. Encouraging preclinical results indicate that stem cell-based treatments may improve the disease outcome due to their multi-therapeutic ability. Mesenchymal Stem Cells (MSCs) are currently considered one of the most promising approaches. Significant improvement in the behavioral outcome after MSC treatment sustained by hydrogel has been demonstrated. However, it is still not known how hydrogel contribute to the delivery of factors secreted from MSCs and what factors are released in situ. Among different mediators secreted by MSCs after seeding into hydrogel, we have found CCL2 chemokine, which could account for the neuroprotective mechanisms of these cells. CCL2 secreted from human MSCs is delivered efficaciously in the lesioned spinal cord acting not only on recruitment of macrophages, but driving also their conversion to an M2 neuroprotective phenotype. Surprisingly, human CCL2 delivered also plays a key role in preventing motor neuron degeneration in vitro and after spinal cord trauma in vivo, with a significant improvement of the motor performance of the rodent SCI models.

【 授权许可】

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