Ming-Hsiao Hu

Influence of age-related degeneration on regenerative potential of human nucleus pulposus cells

Nucleus pulposus (NP) cells, sourced from herniation surgeries, may be used as a cell‐based therapy for intervertebral disc (IVD) degeneration. But, both the regenerative potential of these degenerative adult NP cells and how to stimulate optimum matrix synthesis is not yet clear. The purpose of the current study was to understand the different phenotypic behaviors between degenerative adult NP cells and normal adolescent NP cells. Degenerative adult NP cells produced a significantly higher amount of proteoglycans and collagens than adolescent cells. Insulin‐like growth factor‐1 was the only anabolic cytokine with increased endogenous expression in degenerative adult NP cells. TGF‐β1 treatment of degenerative NP cells promoted matrix synthesis but stimulated too much type I collagen and suppressed type II collagen and aggrecan. Adult degenerative NP cells possess upregulated regenerative potential, but stimulation in addition to TGF‐β1 is needed to enhance matrix productivity and optimize the collagen expression profile.

Vascular Compression Syndrome of Sciatic Nerve Caused by Gluteal Varicosities

Sciatica is defined as pain or discomfort along the regions innervated by the sciatic nerve. Compression or irritation of lumbar spinal roots, most commonly because of lumbar disc herniation or spinal stenosis, causes sciatica in the vast majority of cases. Although it is rather uncommon, many pathologies have reported to cause nondiscogenic sciatica. A 70-year-old woman presented with intractable sciatic pain which was not elicited by posture change or cough. Sitting on the affected side provoked more pain than standing or walking. Magnetic resonance imaging revealed both spondylolisthesis with lumbar stenosis and compression of the gluteal portion of the sciatic nerve by varicotic gluteal veins. Given the atypical presentation of spinal root compression, gluteal vascular compressive neuropathy was suspected. Ligation and resection of varicotic vein resulted in relief of the patients pain. To our knowledge, cases with varicosity-caused sciatica were limited in the literature review.

Lovastatin prevents discography-associated degeneration and maintains the functional morphology of intervertebral discs

BACKGROUND CONTEXT Discography is an important diagnostic approach to identify the painful discs. However, the benefit of discography, a procedure involving needle puncture and injection of the diagnostic agent into the intervertebral disc, is controversial and has been reported to be associated with accelerated degeneration. PURPOSE To investigate the effect of lovastatin on the prevention of degeneration caused by a discography simulation procedure in rat caudal discs. STUDY DESIGN In vivo study using rat caudal discs. METHODS A single flexible 27-gauge needle puncture into rat caudal discs was performed under fluoroscopic monitoring. Different concentrations (0.1, 1, 5, and 10 μM) of lovastatin were prepared and injected into randomly chosen caudal discs. RNA expression of selected genes, histologic, and immunohistochemical staining were performed to evaluate the phenotypic effects of lovastatin on rat caudal discs. RESULTS Simulation of the discography procedure by puncturing the rat caudal discs with a 27-gauge needle and injection of saline solution induced degenerative changes in the nucleus pulposus with minimal damage to the annulus fibrosus. Aggrecan, Type II collagen, and SOX9 expressions were upregulated, whereas Type I collagen expression was significantly suppressed in discs treated with 5 and 10 μM lovastatin. Discs treated with 5 and 10 μM lovastatin were subjected to alcian blue staining and immunohistochemistry that revealed higher levels of glycosaminoglycans and an increase in the number of cells producing S-100 proteins, Type II collagen, and bone morphogenetic protein-2 (BMP-2), respectively. The most effective phenotypic repair was observed in discs treated with 10 μM lovastatin. CONCLUSIONS Intradiscal administration of lovastatin solution upregulated the expressions of BMP-2 and SOX9 and promoted chondrogenesis of rat caudal discs after needle puncture and substance injection. Therefore, we suggest that lovastatin promotes disc repair and can be used as a potential therapeutic agent for biological repair of disc degeneration after the diagnostic discography procedure.

Giant ganglionic cyst of the hip as a rare cause of sciatica

Although ganglionic cysts located at the hip joint are described infrequently, those found in this region are usually small, deep-seated, and asymptomatic. Occasionally, however, a large ganglionic cyst of the hip area is observed that becomes symptomatic following compression of adjacent neurovascular bundles. In this report, the authors describe a 51-year-old man with symptoms of sciatica caused by a giant ganglionic cyst of the posterior hip joint. Because of its intermuscular location, the cyst was not palpable, and was probably misdiagnosed previously as a herniated disc of the lumbar spine. After resection of the cyst, the patients symptoms resolved completely. This case highlights the importance of a detailed clinical examination for patients with multiple degenerative joint diseases.

The influence of oxygen concentration on the extracellular matrix production of human nucleus pulposus cells during isolation-expansion process

Nucleus pulposus (NP) cells locate in the center of avascular intervertebral discs, and thus have presumably adapted to a hypoxic environment. The purpose of this study was to investigate the influences of hypoxic condition, during isolation-expansion of human NP cells, on the cellular proliferation and extracellular matrix (ECM) synthesis in later three-dimensional cultures. Human NP tissues were obtained from patients who underwent lumbar disc surgeries. Immediately after retrieval, NP tissues from each patient were divided into two aliquots for in vitro cultivation either under classical normoxic (21% O2 ) or hypoxic (3.5% O2 ) condition. After isolation-expansion processes, microtissues of NP cells were formed and the analysis was performed after one-week culture. Experiments of pretreatment with TGF-β1 or lovastatin were designed to investigate if the isolation-expansion conditions affect the responsiveness to later exogenous treatments. Hypoxic isolation-expansion stimulated NP cell proliferation during monolayer culture. Hypoxia also upregulated mRNA levels of SOX9 and HIF-1α but downregulated type X collagen as well as improved aggrecan and type II collagen synthesis. Although TGF-β1 had no substantial effect, lovastatin pretreatment showed a greater enhancement on type II collagen expression in hypoxic group. Normoxia negatively affected the biochemical composition of regenerated ECM attributable to downregulation of SOX9 and HIF-1α, while hypoxia enhanced cellular proliferation, improved matrix production, and maintained a functional phenotype of NP cells. Hypoxic isolation-expansion of human NP cells is important to achieve better regenerative cells for later cultivation or cell transplantation.

Slipped capital femoral epiphysis in an adult with panhypopituitarism.

Slipped capital femoral epiphysis usually occurs in children going through a pubertal growth spurt, possibly because the immature proximal femoral physis is unable to bear the shear stress. It commonly occurs in adolescents between 10 and 16 years. Slipped capital femoral epiphysis in adults is uncommon, with only 10 cases reported in the literature. This article presents a case of a 29-year-old man with craniopharyngioma diagnosed when he was 19. He underwent surgery with subtotal tumor excision and postoperative radiotherapy, but received no further treatment for the panhypopituitarism concomitant with the tumor. He reported sudden onset of left hip pain after riding a bicycle and underwent surgical fixation 5 days later. He also underwent hormone replacement therapy, including prednisolone, thyroxin, desmopressin, and testosterone, and regular clinical follow-up. His hip function recovered with a painless gait. At 18-month follow-up, neither osteonecrosis nor contralateral slipped capital femoral epiphysis was noted. Furthermore, bilateral proximal femoral physes were also closed. For stable slippage as in this case, in situ pinning fixation is a commendable method. A high index of suspicion of endocrinal disorder and proper management are essential for successful treatment of adult slipped capital femoral epiphysis.

Optimization of puncture injury to rat caudal disc for mimicking early degeneration of intervertebral disc

The caudal discs of rats have been proposed as a puncture model in which intervertebral disc (IVD) degeneration can be induced and novel therapies can be tested. For biological repair, treatments for ongoing IVD degeneration are ideally administered during the earlier stages. The purpose of this study was to elucidate the optimal puncture needle size for creating a model that mimicked the earlier stages of IVD degeneration. According to the disc height index, histologic score, and MRI grading, a puncture needle sized 21G or larger induced rapid degenerative processes in rat caudal discs during the initial 2–4 weeks. The degenerative changes were severe and continued deteriorating after 4 weeks. Conversely, puncture injury induced by needles sized 25G or smaller also produced degenerative changes in rat caudal discs during initial 2–4 weeks; however, the changes were less severe. Furthermore, the degenerative process became stabilized and showed no further deterioration or spontaneous recovery after 4 weeks. In the discs punctured by 25G needles, the expression of collagen I was increased at 2–4 weeks with a gradually fibrotic transformation thereafter. The expressions of collagen II and SOX9 were enhanced initially but returned to pre‐injury levels at 4–8 weeks. The above‐mentioned findings were more compatible with earlier degeneration in discs punctured by needles sized 25G or smaller than by needles sized 21G or larger, and the appropriate timing for intradiscal administration of proposed therapeutic agents would be 4 weeks or longer after puncture.

In situ forming oxidised hyaluronic acid/adipic acid dihydrazide hydrogel for prevention of epidural fibrosis after laminectomy

Post-operative epidural fibrosis is a biological response after laminectomy that may lead to clinical symptoms, such as radicular pain. An ideal material for prevention of epidural fibrosis should be able to inhibit fibroblast adhesions and reduce formation of scar tissue. An injectable hydrogel would be the material of choice for this purpose, since it could fill an irregular surgical defect completely, gelate in situ and be delivered in a minimally-invasive manner. The objective of this study was to evaluate, in vitro and in vivo, the cytocompatibility and anti-adhesive effect of an oxidised hyaluronic acid/adipic acid dihydrazide (oxi-HA/ADH) hydrogel. Different cell types present in the spine were used to test the cytocompatibility of the hydrogel. The hydrogel extraction medium had no deleterious effects on neural cells (PC-12), but reduced fibroblasts viability (NIH/3T3). Although the hydrogel did not change the release of lactate dehydrogenase from myoblasts (C2C12) and Schwann cells (RSC96), the extraction medium concentration slightly affected the mitochondrial activity of these two cell types. qPCR showed that the hydrogel down-regulated S100a and P4hb expression in NIH/3T3 cells, supporting the hypothesis that the hydrogel might inhibit fibroblast activity. The animal study showed a reduction of scar tissue formation as well as severity of adhesion between scar tissue and the dura mater in a rat laminectomy model. Superficially, the peel-off test showed significantly decreased tenacity. In conclusion, the oxi-HA/ADH hydrogel is a promising injectable and thermosensitive material for prevention of post-operative epidural fibrosis.

Assessment of Change of Shoulder Balance in Patients with Adolescent Idiopathic Scoliosis after Correctional Surgery

To identify factors that influence shoulder balance and to determine whether a model can be made to predict shoulder balance after corrective surgery.