Effect of the combination of mesenchymal stromal cells and chondroitinase ABC on chronic spinal cord injury.

Abstract

Transplantation of mesenchymal stromal cells (MSCs) has been identified as a potential therapeutic modality for treating spinal cord injury (SCI). Degradation of chondroitin sulfate proteoglycans (CSPGs) using the enzyme chondroitinase ABC (chABC) can promote functional recovery after SCI. The effect of the simultaneous administration of MSCs and chABC on chronic SCI was investigated. Sixteen dogs were assigned to one of the following four groups: (i) canine adipose tissue-derived MSCs (cADMSCs), (ii) chABC, (iii) cADMSCs + chABC and (iv) control. Treatments were carried out 3 weeks after SCI; cADMSCs (1 × 10(7) cells suspended in 150 μL of PBS), chABC (5 U/mL, 150 μL), cADMSCs + chABC (1 × 10(7) cells suspended in 150 μL of chABC), or phosphate-buffered saline (150 μL) were injected into the spinal cord at three locations to a depth of 3 mm using a 30-gauge needle. The spinal cord was harvested 8 weeks after transplantation. In a behavioral assessment, dogs treated with cADMSCs + chABC and cADMSCs alone showed significantly better functional recovery 8 weeks after transplantation compared with the control and chABC groups (P < 0.05). In addition, the combination of cADMSCs and chABC increased the expression of digested CSPGs (2B6), β3 tubulin, and NF-M. However, the levels of COX2 (P < 0.05), and tumor necrosis factor-α was higher in the treatment groups than in the control. In conclusion, transplantation of cADMSCs + chABC was more effective in improving clinical signs and neural regeneration, but a strategy for anti-inflammation after the treatment for chronic SCI would be needed for further improvement.

• Authors: Seung Hoon Lee, Yongsun Kim, Daeun Rhew, Minyong Kuk, Mijung Kim, Wan Hee Kim, Oh-Kyeong Kweon
• Journal: Cytotherapy (Cytotherapy) Vol. 17 Issue 10 Pg. 1374-83 (Oct 2015) ISSN: 1477-2566 [Electronic] England
• PMID: 26188966 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Chemical References

• Chondroitin Sulfate Proteoglycans
• Neurofilament Proteins
• Tubulin
• Tumor Necrosis Factor-alpha
• neurofilament protein M
• Cyclooxygenase 2
• Chondroitin ABC Lyase

Topics

• Animals
• Chondroitin ABC Lyase (administration & dosage)
• Chondroitin Sulfate Proteoglycans (metabolism)
• Combined Modality Therapy
• Cyclooxygenase 2 (metabolism)
• Dogs
• Female
• Male
• Mesenchymal Stem Cell Transplantation (methods)
• Mesenchymal Stem Cells (metabolism)
• Nerve Regeneration
• Neurofilament Proteins (metabolism)
• Recovery of Function
• Spinal Cord Injuries (drug therapy, surgery, therapy)
• Treatment Outcome
• Tubulin (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)