Percutaneous transplantation of human umbilical cord blood–derived multipotent stem cells in a canine model of spinal cord injury

Laboratory investigation

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  • 1 Departments of Veterinary Surgery and
  • 2 Veterinary Anatomy, Konkuk University; and
  • 3 Seoul Cord Blood Bank, Histostem Company, Seoul, Republic of Korea
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Object

The authors describe a method for percutaneous transplantation of human umbilical cord blood (hUCB)–derived multipotent stem cells (MSCs) under fluoroscopic guidance. The investigators then tested whether percutaneous transplantation of hUCB-derived MSCs improved neurological functional recovery after acute spinal cord injury (SCI).

Methods

The authors induced SCI in 10 dogs by percutaneous balloon compression. The 10 injured dogs were assigned randomly to the following groups (2 dogs each): Group 1, evaluated 2 weeks after sham transplantation; Group 2, evaluated 2 weeks after transplantation; Group 3, evaluated 4 weeks after sham transplantation; Group 4, evaluated 4 weeks after transplantation; and Group 5, evaluated 4 weeks after multispot transplantations. The dogs with sham transplantation (Groups 1 and 3) received the same volume of saline, as a control. A spinal needle was advanced into the spinal canal, and the investigators confirmed that the end of the spinal needle was located in the ventral part of spinal cord parenchyma by using contrast medium under fluoroscopic guidance. The hUCB-derived MSCs were transplanted into the cranial end of the injured segment in 6 injured dogs at 7 days after SCI.

Results

Two dogs in Group 2 showed no improvement until 2 weeks after transplantation. Three of 4 dogs (Groups 4 and 5) that received cellular transplants exhibited gradual improvement in hindlimb locomotion from 3 weeks after cell transplantation. The CM-DiI–labeled hUCB-derived MSCs were observed in the spinal cord lesions at 4 weeks posttransplantation and exerted a significant beneficial effect by reducing cyst and injury size. The transplanted cells were positive for NeuN, glial fibrillary acidic protein, and von Willebrand factor.

Conclusions

The percutaneous transplantation technique described here can be easily performed, and it differs from previous techniques by avoiding surgical exposure and allowing cells to be more precisely transplanted into the spinal cord. This technique has many potential applications in the treatment of human SCI by cell transplantation. The results also suggest that transplantation of hUCB-derived MSCs may have therapeutic effects that decrease cavitation for acute SCI.

Abbreviations used in this paper: GFAP = glial fibrillary acidic protein; hUCB = human umbilical cord blood; MNC = mononuclear cell; MSC = multipotent stem cell; PBS = phosphate-buffered saline; SCI = spinal cord injury; SEP = sensory evoked potential; vWF = von Willebrand factor.

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Contributor Notes

Address correspondence to: Hwi-Yool Kim, Ph.D., Department of Veterinary Surgery, College of Veterinary Medicine, Konkuk University Room No 222, #1 Hwayang-Dong, Kwangjin-Gu, Seoul 143-701, South Korea. email: hykim@konkuk.ac.kr.
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