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J Control Release. 2018 May 28;278:49-56. doi: 10.1016/j.jconrel.2018.03.034. Epub 2018 Apr 3.

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

Author information

1
Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, Milano 20156, Italy.
2
Department of Environmental Health Sciences, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, Milan 20156, Italy.
3
EPIGET LAB, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy; Unit of Rigenerative Medicine - Cell Factory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
4
Department of Chemistry, Materials and Chemical engineering "Giulio Natta", Politecnico di Milano, via Mancinelli 7, Milano 20131, Italy.
5
Department of Oncology, IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", via La Masa 19, Milan 20156, Italy.
6
Unit of Rigenerative Medicine - Cell Factory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
7
Department of Neuroscience, IRCCS Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, Milano 20156, Italy. Electronic address: pietro.veglianese@marionegri.it.

Abstract

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.

KEYWORDS:

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

PMID:
29621597
DOI:
10.1016/j.jconrel.2018.03.034
[Indexed for MEDLINE]

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