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Intravenous infusion of adipose-derived stem/stromal cells improves functional recovery of rats with spinal cord injury.
Cytotherapy. 2017 07; 19(7):839-848.C

Abstract

BACKGROUND AIMS

Adipose tissue has therapeutic potential for spinal cord injury (SCI) because it contains multipotent cells known as adipose-derived stem/stromal cells (ASCs). In this study, we attempted intravenous ASC transplantation in rats with SCI to examine the effect on functional recovery.

METHODS

ASCs (2.5 × 106) were intravenously infused into SCI rats, after which hindlimb motor function was evaluated. Distribution of transplanted ASCs was investigated and growth factor/cytokine levels were determined.

RESULTS

Intravenous transplantation of ASCs promoted the functional recovery in SCI rats and reduced the area of spinal cord cavitation. A distribution study revealed that ASCs gradually accumulated at the site of injury, but long-term survival of these cells was not achieved. Levels of growth factors increased only slightly in the spinal cord after ASC transplantation. Unexpectedly, cytokine-induced neutrophil chemoattractant (CINC)-1 showed a transient but substantial increase in the spinal cord tissue and blood of the ASC group. CINC-1 was secreted by ASCs in vitro, and the sponge implantation assay showed that CINC-1 and ASCs induced angiogenesis. CINC-1 promoted functional recovery in SCI rats, which was similar to the ASCs. Expression of glial cell line-derived neurotrophic factor was greater in the ASC group than in the CINC-1 group, although both promoted extracellular signal-regulated kinase (ERK)1/2 phosphorylation; Akt phosphorylation was enhanced in the spinal cord after ASC transplantation.

CONCLUSIONS

Our findings indicated that intravenously transplanted ASCs gradually accumulated in the injured spinal cord, where cytokines such as CINC-1 activated ERK1/2 and Akt, leading to functional recovery.

Authors+Show Affiliations

Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan. Electronic address: yuki-o@marianna-u.ac.jp.Institute of Medical Science, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan.Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.Institute for Animal Experimentation, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan.Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.Department of Pharmacology, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan.Institute of Medical Science, St. Marianna University Graduate School of Medicine, Kawasaki, Kanagawa, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28478920

Citation

Ohta, Yuki, et al. "Intravenous Infusion of Adipose-derived Stem/stromal Cells Improves Functional Recovery of Rats With Spinal Cord Injury." Cytotherapy, vol. 19, no. 7, 2017, pp. 839-848.
Ohta Y, Hamaguchi A, Ootaki M, et al. Intravenous infusion of adipose-derived stem/stromal cells improves functional recovery of rats with spinal cord injury. Cytotherapy. 2017;19(7):839-848.
Ohta, Y., Hamaguchi, A., Ootaki, M., Watanabe, M., Takeba, Y., Iiri, T., Matsumoto, N., & Takenaga, M. (2017). Intravenous infusion of adipose-derived stem/stromal cells improves functional recovery of rats with spinal cord injury. Cytotherapy, 19(7), 839-848. https://doi.org/10.1016/j.jcyt.2017.04.002
Ohta Y, et al. Intravenous Infusion of Adipose-derived Stem/stromal Cells Improves Functional Recovery of Rats With Spinal Cord Injury. Cytotherapy. 2017;19(7):839-848. PubMed PMID: 28478920.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intravenous infusion of adipose-derived stem/stromal cells improves functional recovery of rats with spinal cord injury. AU - Ohta,Yuki, AU - Hamaguchi,Akemi, AU - Ootaki,Masanori, AU - Watanabe,Minoru, AU - Takeba,Yuko, AU - Iiri,Taroh, AU - Matsumoto,Naoki, AU - Takenaga,Mitsuko, Y1 - 2017/05/03/ PY - 2016/12/28/received PY - 2017/04/05/revised PY - 2017/04/07/accepted PY - 2017/5/10/pubmed PY - 2018/2/13/medline PY - 2017/5/9/entrez KW - adipose-derived stem/stromal cells KW - cytokine-induced neutrophil chemoattractant-1 KW - intravenous infusion KW - spinal cord injury SP - 839 EP - 848 JF - Cytotherapy JO - Cytotherapy VL - 19 IS - 7 N2 - BACKGROUND AIMS: Adipose tissue has therapeutic potential for spinal cord injury (SCI) because it contains multipotent cells known as adipose-derived stem/stromal cells (ASCs). In this study, we attempted intravenous ASC transplantation in rats with SCI to examine the effect on functional recovery. METHODS: ASCs (2.5 × 106) were intravenously infused into SCI rats, after which hindlimb motor function was evaluated. Distribution of transplanted ASCs was investigated and growth factor/cytokine levels were determined. RESULTS: Intravenous transplantation of ASCs promoted the functional recovery in SCI rats and reduced the area of spinal cord cavitation. A distribution study revealed that ASCs gradually accumulated at the site of injury, but long-term survival of these cells was not achieved. Levels of growth factors increased only slightly in the spinal cord after ASC transplantation. Unexpectedly, cytokine-induced neutrophil chemoattractant (CINC)-1 showed a transient but substantial increase in the spinal cord tissue and blood of the ASC group. CINC-1 was secreted by ASCs in vitro, and the sponge implantation assay showed that CINC-1 and ASCs induced angiogenesis. CINC-1 promoted functional recovery in SCI rats, which was similar to the ASCs. Expression of glial cell line-derived neurotrophic factor was greater in the ASC group than in the CINC-1 group, although both promoted extracellular signal-regulated kinase (ERK)1/2 phosphorylation; Akt phosphorylation was enhanced in the spinal cord after ASC transplantation. CONCLUSIONS: Our findings indicated that intravenously transplanted ASCs gradually accumulated in the injured spinal cord, where cytokines such as CINC-1 activated ERK1/2 and Akt, leading to functional recovery. SN - 1477-2566 UR - https://www.unboundmedicine.com/medline/citation/28478920/Intravenous_infusion_of_adipose_derived_stem/stromal_cells_improves_functional_recovery_of_rats_with_spinal_cord_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1465-3249(17)30544-3 DB - PRIME DP - Unbound Medicine ER -