Systemic administration of human adipose-derived stem cells reverts nociceptive hypersensitivity in an experimental model of neuropathy

Paola Sacerdote, Stefania Niada, Silvia Franchi, Elena Arrigoni, Alice Rossi, Vijay Yenagi, Laura De Girolamo, Alberto Emilio Panerai, Anna Teresa Brini

Research output: Contribution to journalArticle

Abstract

Over the last decade, it has been proved that mesenchymal stem cells (MSCs) elicit anti-inflammatory effects. MSCs from adipose tissue (hASCs) differentiate into cells of the mesodermal lineage and transdifferentiate into ectodermal-origin cells. Although there are various etiologies to chronic pain, one common feature is that painful states are associated with increased inflammation. We believe in hASCs as a therapeutic tool also in pathologies involving neuroinflammation and neuronal tissue damage. We have investigated the effect of hASCs injected in a model of neuropathic pain [(mouse sciatic nerve chronic constriction injury (CCI)]. hASCs from 5 donors were characterized, and no major differences were depicted. hASCs were cryopreserved and grown on demand. About 1×106, 3×106, and 6×106 hASCs were intravenously injected into normal immunocompetent mice. No mouse died, and no macroscopic toxicity or behavioral changes were observed, confirming the safety of hASCs. hASCs, intravenously (i.v.) injected into C57BL/6 mice when the neuropathic pain was already established, induced a significant reduction in mechanical allodynia and a complete reversion of thermal hyperalgesia in a dose-response fashion, already 1 day after administration. Moreover, the hASCs effect can be boosted by repeated administrations, allowing a prolonged therapeutic effect. Treatment decreased the level of the CCI-induced proinflammatory cytokine interleukin (IL)-1β and activated the anti-inflammatory cytokine IL-10 in the lesioned nerve. hASCs treatment also restored normal inducible nitric oxide synthase expression in the spinal cord of CCI animals. Our data suggest that hASCs are worthy of further studies as an anti-inflammatory therapy in the treatment of neuropathic pain or chronic inflammatory diseases.

Original languageEnglish
Pages (from-to)1252-1263
Number of pages12
JournalStem Cells and Development
Volume22
Issue number8
DOIs
Publication statusPublished - Apr 15 2013

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Hypersensitivity
Theoretical Models
Stem Cells
Neuralgia
Constriction
Anti-Inflammatory Agents
Hyperalgesia
Mesenchymal Stromal Cells
Wounds and Injuries
Cytokines
Therapeutics
Therapeutic Uses
Nitric Oxide Synthase Type II
Cell Lineage
Sciatic Nerve
Interleukin-1
Inbred C57BL Mouse
Chronic Pain
Interleukin-10
Adipose Tissue

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Hematology

Cite this

Systemic administration of human adipose-derived stem cells reverts nociceptive hypersensitivity in an experimental model of neuropathy. / Sacerdote, Paola; Niada, Stefania; Franchi, Silvia; Arrigoni, Elena; Rossi, Alice; Yenagi, Vijay; De Girolamo, Laura; Panerai, Alberto Emilio; Brini, Anna Teresa.

In: Stem Cells and Development, Vol. 22, No. 8, 15.04.2013, p. 1252-1263.

Research output: Contribution to journalArticle

Sacerdote, Paola ; Niada, Stefania ; Franchi, Silvia ; Arrigoni, Elena ; Rossi, Alice ; Yenagi, Vijay ; De Girolamo, Laura ; Panerai, Alberto Emilio ; Brini, Anna Teresa. / Systemic administration of human adipose-derived stem cells reverts nociceptive hypersensitivity in an experimental model of neuropathy. In: Stem Cells and Development. 2013 ; Vol. 22, No. 8. pp. 1252-1263.
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