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

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>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).</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p></jats:sec>

Schwann cell-like remyelination following transplantation of human umbilical cord blood (hUCB)-derived mesenchymal stem cells in dogs with acute spinal cord injury

“…However, we previously reported that these hUCBMSCs survived in dogs with SCI for 4 weeks [9]. Further, Saporta et al [5] have previously reported that intravenously infused hUCB cells survived in the injured spinal cord until 3 weeks after the infusion and this had improved motor functions in a rat after SCI.…”

“…Characterization and differentiation of isolated hUCB-MSCs were performed in another study using the same cell source and isolation technique [7,10,16]. It was also suggested that these hUCB-MSCs are capable of differentiating into neural cells in vitro [17] and in vivo [9,16]. The hUCB-MSCs were provided for pure research purposes by the Seoul Cord Bank (Histostem Co., Ltd., Seoul, Korea).…”

“…All procedures followed the methods described previously [9]. Seven injured dogs (No 4-10) were transplanted with hUCBMSCs.…”

“…hUCB-MSCs were prepared according to methods previously described [7,9], with some modification. In brief, freshly collected human UCB samples from full-term deliveries were obtained after obtaining written, informed donor consent.…”

“…Further, these hUBC-MSCs are readily available and less immunogenic compared to other sources [7,8]. We previously reported that hUCB-MSCs could improve motor function in injured dogs [9], while, in a human trial, a female patient with chronic SCI was reported to show slight improvement in sensory and motor functions after hUCB-MSC transplantation [10].…”