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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:Background contextEndplate (EP) injury plays critical roles in painful IVD degeneration since Modic changes (MCs) are highly associated with pain. Models of EP microfracture that progress to painful conditions are needed to better understand pathophysiological mechanisms and screen therapeutics.PurposeEstablish in vivo rat lumbar EP microfracture model and assess crosstalk between IVD, vertebra and spinal cord.Study design/settingIn vivo rat EP microfracture injury model with characterization of IVD degeneration, vertebral remodeling, spinal cord substance P (SubP), and pain-related behaviors.MethodsEP-injury was induced in 5 month-old male Sprague-Dawley rats L4-5 and L5-6 IVDs by puncturing through the cephalad vertebral body and EP into the NP of the IVDs followed by intradiscal injections of TNFα (n=7) or PBS (n=6), compared with Sham (surgery without EP-injury, n=6). The EP-injury model was assessed for IVD height, histological degeneration, pain-like behaviors (hindpaw von Frey and forepaw grip test), lumbar spine MRI and μCT, and spinal cord SubP.ResultsSurgically-induced EP microfracture with PBS and TNFα injection induced IVD degeneration with decreased IVD height and MRI T2 signal, vertebral remodeling, and secondary damage to cartilage EP adjacent to the injury. Both EP injury groups showed MC-like changes around defects with hypointensity on T1-weighted and hyperintensity on T2-weighted MRI, suggestive of MC type 1. EP injuries caused significantly decreased paw withdrawal threshold, reduced axial grip, and increased spinal cord SubP, suggesting axial spinal discomfort and mechanical hypersensitivity and with spinal cord sensitization.ConclusionsSurgically-induced EP microfracture can cause crosstalk between IVD, vertebra, and spinal cord with chronic pain-like conditions.Clinical significanceThis rat EP microfracture model was validated to induce broad spinal degenerative changes that may be useful to improve understanding of MC-like changes and for therapeutic screening.

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.

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

Publications

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

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