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Human-induced pluripotent stem cells generated from intervertebral disc cells improve neurologic functions in spinal cord injury.

ABSTRACT: Induced pluripotent stem cells (iPSCs) have emerged as a promising cell source for immune-compatible cell therapy. Although a variety of somatic cells have been tried for iPSC generation, it is still of great interest to test new cell types, especially those which are hardly obtainable in a normal situation.In this study, we generated iPSCs by using the cells originated from intervertebral disc which were removed during a spinal operation after spinal cord injury. We investigated the pluripotency of disc cell-derived iPSCs (diPSCs) and neural differentiation capability as well as therapeutic effect in spinal cord injury.The diPSCs displayed similar characteristics to human embryonic stem cells and were efficiently differentiated into neural precursor cells (NPCs) with the capability of differentiation into mature neurons in vitro. When the diPSC-derived NPCs were transplanted into mice 9 days after spinal cord injury, we detected a significant amelioration of hindlimb dysfunction during follow-up recovery periods. Histological analysis at 5 weeks after transplantation identified undifferentiated human NPCs (Nestin(+)) as well as early (Tuj1(+)) and mature (MAP2(+)) neurons derived from the transplanted NPCs. Furthermore, NPC transplantation demonstrated a preventive effect on spinal cord degeneration resulting from the secondary injury.This study revealed that intervertebral discs removed during surgery for spinal stabilization after spinal cord injury, previously considered a "waste" tissue, may provide a unique opportunity to study iPSCs derived from difficult-to-access somatic cells and a useful therapeutic resource for autologous cell replacement therapy in spinal cord injury.

SUBMITTER: Oh J

PROVIDER: S-EPMC4529688 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Human-induced pluripotent stem cells generated from intervertebral disc cells improve neurologic functions in spinal cord injury.

Oh Jinsoo J Lee Kang-In KI Kim Hyeong-Taek HT You Youngsang Y Yoon Do Heum DH Song Ki Yeong KY Cheong Eunji E Ha Yoon Y Hwang Dong-Youn DY

Stem cell research & therapy 20150624

<h4>Introduction</h4>Induced pluripotent stem cells (iPSCs) have emerged as a promising cell source for immune-compatible cell therapy. Although a variety of somatic cells have been tried for iPSC generation, it is still of great interest to test new cell types, especially those which are hardly obtainable in a normal situation.<h4>Methods</h4>In this study, we generated iPSCs by using the cells originated from intervertebral disc which were removed during a spinal operation after spinal cord in ...[more]

PMID: 26104416

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Project description:BackgroundSpinal growth modulation has been proposed as a non-fusion strategy for treatment of idiopathic scoliosis, although the effect of this treatment modality on intervertebral disc health has not been evaluated in detail. The objectives of this in vivo study were to assess the creation of three-dimensional spinal deformity during six months of growth modulation compared with that in sham-surgery controls, and to compare, with use of magnetic resonance imaging (MRI), gross morphological, histological, and biochemical analyses, disc health between control animals and animals treated with a spinal tether.MethodsSix immature Yucatan mini-pigs underwent anterior spinal instrumentation with vertebral screws connected by a polyethylene tether over four consecutive thoracic vertebrae (T8-T11). An additional six animals underwent sham surgery (screw placement only [the control group]). Radiographs were obtained preoperatively, postoperatively, and monthly thereafter during six months of growth. Computed tomography (CT) and MRI studies were performed ex vivo, and the spines were sectioned for histological and biochemical analyses. Multivariate analysis of variance (MANOVA) was used to compare six-month postoperative data between the control and tethered animals, with the alpha level of significance set at 0.05.ResultsRadiographs and CT images demonstrated the creation of significant three-dimensional deformity (p < 0.013) in the tethered animals compared with the controls. Macroscopic, MRI, and histological evaluation revealed no signs of disc degeneration, with a bulging gelatinous nucleus pulposus, discrete fibrous anular lamellae, and uniformly hyperintense T2-signal intensity within the nuclei pulposi. Biochemical analysis demonstrated no significant difference in the nuclei pulposus between the tethered and control vertebrae; however, the water content (p < 0.001) of both sides of the anulus fibrosus and the glycosaminoglycan content (p < 0.001) of the left side of the anulus fibrosus differed significantly between the two groups.ConclusionsSix months of spinal growth modulation created significant spinal deformity in all three planes compared with what was found in the sham-surgery controls. Although disc health was qualitatively maintained, quantitative changes in the anulus fibrosus water content and the disc height were observed on the side opposite to the tether. These changes likely represent metabolic responses of the discs to compressive loads generated by the flexible tether.

Project description:Back pain associated with symptomatic disc degeneration is a common clinical condition. Intervertebral disc (IVD) cell apoptosis and senescence increase with aging and degeneration. Repopulating the IVD with cells that could produce and maintain extracellular matrix would be an alternative therapy to surgery. The objective of this study was to determine the potential of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) as a novel cell source for disc repair. In this study, we intended to confirm the potential for hUCB-MSCs to differentiate and display a chondrocyte-like phenotype after culturing in micromass and after injection into the rabbit IVD explant culture. We also wanted to confirm hUCB-MSC survival after transplantation into the IVD explant culture.This study consisted of micromass cultures and in vitro rabbit IVD explant cultures to assess hUCB-MSC survival and differentiation to display chondrocyte-like phenotype. First, hUCB-MSCs were cultured in micromass and stained with Alcian blue dye. Second, to confirm cell survival, hUCB-MSCs were labeled with an infrared dye and a fluorescent dye before injection into whole rabbit IVD explants (host). IVD explants were then cultured for 4 wks. Cell survival was confirmed by two independent techniques: an imaging system detecting the infrared dye at the organ level and fluorescence microscopy detecting fluorescent dye at the cellular level. Cell viability was assessed by staining the explant with CellTracker green, a membrane-permeant tracer specific for live cells. Human type II collagen gene expression (from the graft) was assessed by polymerase chain reaction.We have shown that hUCB-MSCs cultured in micromass are stained blue with Alcian blue dye, which suggests that proteoglycan-rich extracellular matrix is produced. In the cultured rabbit IVD explants, hUCB-MSCs survived for at least 4 wks and expressed the human type II collagen gene, suggesting that the injected hUCB-MSCs are differentiating into a chondrocyte-like lineage.This study demonstrates the abiity of hUBC-MSCs to survive and assume a chondrocyte-like phenotype when injected into the rabbit IVD. These data support the potential for hUBC-MSCs as a cell source for disc repair. Further measures of the host response to the injection and studies in animal models are needed before trials in humans.

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Human-induced pluripotent stem cells generated from intervertebral disc cells improve neurologic functions in spinal cord injury.

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Human-induced pluripotent stem cells generated from intervertebral disc cells improve neurologic functions in spinal cord injury.

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