Korean J Physiol Pharmacol.  2012 Dec;16(6):405-411. 10.4196/kjpp.2012.16.6.405.

Effects of Human Mesenchymal Stem Cell Transplantation Combined with Polymer on Functional Recovery Following Spinal Cord Hemisection in Rats

• Choi JS
• Leem JW
• Lee KH
• Kim SS
• Suh-Kim H
• Jung SJ
• Kim UJ
• Lee BH

• KMID: 2285449
• DOI: http://doi.org/10.4196/kjpp.2012.16.6.405

Abstract

The spontaneous axon regeneration of damaged neurons is limited after spinal cord injury (SCI). Recently, mesenchymal stem cell (MSC) transplantation was proposed as a potential approach for enhancing nerve regeneration that avoids the ethical issues associated with embryonic stem cell transplantation. As SCI is a complex pathological entity, the treatment of SCI requires a multipronged approach. The purpose of the present study was to investigate the functional recovery and therapeutic potential of human MSCs (hMSCs) and polymer in a spinal cord hemisection injury model. Rats were subjected to hemisection injuries and then divided into three groups. Two groups of rats underwent partial thoracic hemisection injury followed by implantation of either polymer only or polymer with hMSCs. Another hemisection-only group was used as a control. Behavioral, electrophysiological and immunohistochemical studies were performed on all rats. The functional recovery was significantly improved in the polymer with hMSC-transplanted group as compared with control at five weeks after transplantation. The results of electrophysiologic study demonstrated that the latency of somatosensory-evoked potentials (SSEPs) in the polymer with hMSC-transplanted group was significantly shorter than in the hemisection-only control group. In the results of immunohistochemical study, beta-gal-positive cells were observed in the injured and adjacent sites after hMSC transplantation. Surviving hMSCs differentiated into various cell types such as neurons, astrocytes and oligodendrocytes. These data suggest that hMSC transplantation with polymer may play an important role in functional recovery and axonal regeneration after SCI, and may be a potential therapeutic strategy for SCI.

Keyword

Electrophysiology; Mesenchymal stem cells; Polymer; Spinal cord injury

MeSH Terms

Animals
Astrocytes
Axons
Electrophysiology
Embryonic Stem Cells
Humans
Mesenchymal Stem Cell Transplantation
Mesenchymal Stromal Cells
Nerve Regeneration
Neurons
Oligodendroglia
Polymers
Rats
Regeneration
Spinal Cord
Spinal Cord Injuries
Transplants
Polymers

Figure

• 

  Fig. 1 Behavioral effects of hMSC transplantation. The behavior in hemisected rats without transplantation (n=19), with polymer transplantation (n=21), and with polymer combined with hMSC transplantation (n=22) was tested before hemisection surgery and after 1 d, 4 d, and once a week from one to eight weeks after hemisection surgery. (A) The polymer and hMSC-transplanted group significantly improved hindlimb performance in injured (left) legs at five weeks after transplantation. (B) In injured (left) hindlimb, the PWT was significantly different at five and eight weeks after transplantation (↓ or ↑: hemisection or transplantation time, *p<0.05).

• 

  Fig. 2 Representative wave forms of somatosensory evoked potentials (A), and motor evoked potentials (B) at different intensity stimulations.

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  Fig. 3 In vivo electrophysiological effects of hMSCs transplantation. (A, B) Latencies and amplitudes of SSEPs. The P1-peak latencies in polymer with hMSC group were shorter than that with the hemisection group on the injured side (A). (C, D) Latencies and amplitudes of MEPs. P1-peak amplitudes in polymer with hMSC were significantly higher than in hemisection group on the injured side (C). Asterisks indicate statistically significant differences compared to the hemisection-only group, based on Dunnett's post-hoc multiple comparison test (*p<0.05).

• 

  Fig. 4 Staining with X-gal. (A) X-gal-positive cells were observed around the injury site and in adjacent sites, indicating that transplanted cells had migrated. (B~D) High magnification of box B, C, D in A (arrowhead: X-gal positive cells). (E) The number of X-gal-positive cells along the whole section (rostral, injured, and caudal sites).

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  Fig. 5 Double staining of β-gal and Tau, GFAP or APC analyzed by confocal microscopy. (A, D, G) β-gal-positive cells. (B, E, H) Tau, GFAP, APC-positive cells. (C, F, I) merged.

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