Experimental reconstruction of the injured spinal cord

• Autorzy: Jendelova P.
• Języki publikacji: EN

Abstrakty

EN

Tremendous efforts have been made to ameliorate and improve locomotor function after spinal cord injury (SCI) by the transplantation of various types of stem cells. In our study we compared the use of non-neurogenic stem cells – bone marrow stromal cells (MSCs), an immortalized stem cell line (SPCs) derived from human fetal spinal cord tissue or human induced pluripotent stem cell-derived neural precursors (iPS-NPs) – for the treatment of a balloon-induced spinal cord compression lesion. Suspensions of stem cells were implanted into the lesion one week after SCI, while the control groups were injected with saline. Locomotor and sensitivity tests were performed weekly for two months. Animals transplanted with any cell type displayed significant motor and sensory improvement compared to the controls. Morphometric evaluation showed that the white matter was spared in all grafted animals when compared to controls, while the gray matter was spared only in animals implanted with MSCs or iPS-NPs. Two months post-implantation (PI), all types of grafted cells survived in the lesion; however, MSCs, unlike iPS-NPs and SPCs, did not differentiate nor communicate with the host tissue. Compared to SPCs, which partially filled the lesion cavity, iPS-NPs interacted more with the host tissue. Besides differentiating into MAP2-, 5TH- and Dcx-positive neurons, iPS-NPs differentiated into CNPase+ oligodendrocytes. A few cells expressed ChAT, while others were DARPP32+ . SPCs expressed mainly GFAP; however, already at two months PI we found 25% of the cells to be positive for Nkx 6.1, and at four months PI the cells were positive for ChAT and Islet2, motor neuron-specific markers. qPCR revealed the increased expression of rat and human neurotrophin genes as well as human motor neuron-specific genes. Based on staining for GAP43, SPCs cells supported endogenous neurite sprouting and regeneration. Another important therapeutic goal is treating chronic SCI, possibly by a combination of stem cells and bridging scaffolds. Hydrogel bridges seeded with MSCs were implanted into SCI one month after injury. The implanted rats were behaviorally tested, then sacrificed 6 months PI and the spinal cord lesions histologically evaluated. The hydrogels adhered well to the surrounding tissue and completely filled the post-traumatic cavity. MSCs survived in the hydrogel, and neurofilaments, blood vessels and Schwann cells infiltrated the implant. Combined therapy also prevented tissue atrophy, while behavioral analysis showed an improvement in rats with combined treatment, compared with the control group. Our results demonstrate that the transplantation of neurogenic as well as non-neurogenic stem cells into the lesioned rat spinal cord improves functional outcome by providing trophic support to the spared axons in the injured tissue. Neurogenic stem cells have the ability to interact with the host tissue and differentiate into a more mature phenotype, such as motor neurons. Treatment of chronic spinal cord injury will require a combination of cell therapy and lesion bridging. Supported by IAA500390902, GA CR: P304/12/1370, GA CR: P108/10/1560.

Słowa kluczowe

EN

experimental reconstruction; reconstruction; spinal cord; spinal cord injury; transplantation; stem cell; bone marrow; stromal cell; treatment

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.164

Twórcy

autor

Jendelova P.

• Institute of Experimental Medicine, ASCR, Prague, Czech Republic
• Department of Neuroscience, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic