Multipotent adult progenitor cells, but not tissue inhibitor of matrix metalloproteinase-3, increase tissue sparing and reduce urological complications following spinal cord injury

James M. Jones, Marc A. Depaul, Cynthia Gregory, Bradley T. Lang, Hua Xie, Meihua Zhu, Michael Rutten, Robert W. Mays, Sarah A. Busch, Shibani Pati, Kenton Gregory

Research output: Contribution to journalArticle

Abstract

Following spinal cord injury (SCI), inflammation amplifies damage beyond the initial insult, providing an opportunity for targeted treatments. An ideal protective therapy would reduce both edema within the lesion area and the activation/infiltration of detrimental immune cells. Previous investigations demonstrated the efficacy of intravenous injection of multipotent adult progenitor cells (MAPC ® ) to modulate immune response following SCI, leading to significant improvements in tissue sparing, locomotor and urological functions. Separate studies have demonstrated that tissue inhibitor of matrix metalloproteinase-3 (TIMP3) reduces blood-brain barrier permeability following traumatic brain injury in a mouse model, leading to improved functional recovery. This study examined whether TIMP3, delivered alone or in concert with MAPC cells, improves functional recovery from a contusion SCI in a rat model. The results suggest that intravenous delivery of MAPC cell therapy 1 day following acute SCI significantly improves tissue sparing and impacts functional recovery. TIMP3 treatment provided no significant benefit, and further, when co-administered with MAPC cells, it abrogated the therapeutic effects of MAPC cell therapy. Importantly, this study demonstrated for the first time that acute treatment of SCI with MAPC cells can significantly reduce the incidence of urinary tract infection (UTI) and the use of antibiotics for UTI treatment.

Original languageEnglish (US)
Pages (from-to)1416-1427
Number of pages12
JournalJournal of Neurotrauma
Volume36
Issue number9
DOIs
StatePublished - May 1 2019

Fingerprint

Tissue Inhibitor of Metalloproteinase-3
Matrix Metalloproteinase 3
Spinal Cord Injuries
Stem Cells
Cell- and Tissue-Based Therapy
Urinary Tract Infections
Myelitis
Therapeutics
Contusions
Therapeutic Uses
Blood-Brain Barrier
Intravenous Injections
Permeability
Edema
Anti-Bacterial Agents
Incidence

Keywords

  • cell therapy
  • MAPC
  • neuroprotection
  • spinal cord injury
  • TIMP3
  • urinary tract infection

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Multipotent adult progenitor cells, but not tissue inhibitor of matrix metalloproteinase-3, increase tissue sparing and reduce urological complications following spinal cord injury. / Jones, James M.; Depaul, Marc A.; Gregory, Cynthia; Lang, Bradley T.; Xie, Hua; Zhu, Meihua; Rutten, Michael; Mays, Robert W.; Busch, Sarah A.; Pati, Shibani; Gregory, Kenton.

In: Journal of Neurotrauma, Vol. 36, No. 9, 01.05.2019, p. 1416-1427.

Research output: Contribution to journalArticle

Jones, James M. ; Depaul, Marc A. ; Gregory, Cynthia ; Lang, Bradley T. ; Xie, Hua ; Zhu, Meihua ; Rutten, Michael ; Mays, Robert W. ; Busch, Sarah A. ; Pati, Shibani ; Gregory, Kenton. / Multipotent adult progenitor cells, but not tissue inhibitor of matrix metalloproteinase-3, increase tissue sparing and reduce urological complications following spinal cord injury. In: Journal of Neurotrauma. 2019 ; Vol. 36, No. 9. pp. 1416-1427.
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