Repair, regenerative and supportive therapies of the annulus fibrosus: achievements and challenges

Lumbar discectomy is a very effective therapy for neurological decompression in patients suffering from sciatica due to hernia nuclei pulposus. However, high recurrence rates and persisting post-operative low back pain in these patients require serious attention. In the past decade, tissue engineering strategies have been developed mainly targeted to the regeneration of the nucleus pulposus (NP) of the intervertebral disc. Accompanying techniques that deal with the damaged annulus fibrous are now increasingly recognised as mandatory in order to prevent re-herniation to increase the potential of NP repair and to confine NP replacement therapies. In the current review, the requirements, achievements and challenges in this quickly emerging field of research are discussed

Mechanical circulatory support with left ventricular assist devices induces increased expression of stem cell factor and its receptor

Introduction: Previous studies have demonstrated the involvement of mast cells (MCs) in cardiac remodeling during heart failure. LVADs cause an influx of MCs into the failing heart, but the underlying mechanism is unknown. We hypothesize that stem cell factor (SCF) induces migration of MCs to the heart. This study investigates the potential role of SCF and its receptor (C-Kit) in promoting the recruitment of stem cell derived MCs during heart failure and following LVAD support. Methods: Myocardial samples were collected from 10 patients undergoing LVAD implantation (Pre-LVAD) paired with samples taken at the time of heart transplantation (Post-LVAD). Biopsies of 4 normal hearts served as controls. We assessed gene expression of SCF and C-Kit. Additionally, we stained for SCF, C-Kit and tryptase protein and utilized In-situ hybridization to determine the origin of SCF. Results: Real-time PCR: SCF mRNA is significantly increased (P<0.01) following mechanical circulatory support as compared to paired heart failure tissue. C-Kit mRNA was significantly increased post-LVAD, as compared to normal tissues (p<0.05). Immunohistochemistry: The C-Kit protein was only expressed on cardiac mast cells. In-Situ hybridization: SCF mRNA was found in endothelial cells, myocytes and interstitial cells. This was confirmed by antibody staining for the SCF protein. Conclusions: LVADs cause an increase of SCF and C-Kit gene expression during unloading. SCF appears to be an important mechanism for the recruitment and maturation of MCs involved in cardiac remodeling, and we suggest that pharmacologic or biologic modification of SCF may provide a new therapeutic path for heart failure treatment

The possible role of a cardiac mast cell derived protease during adverse cardiac remodeling

Introduction: The role of cardiac mast cells (MC) in the progression to heart failure has recently become increasingly evident. Cathepsin g is a neutrophil- and mast cell- derived protease, which can convert angiotensin I to angiotensin II and thereby activate the TGF-β pathway resulting in myocyte necrosis, hypertrophy and increased fibrosis. This study focuses on mast cell-derived cathepsin g in the human heart during heart failure and following mechanical unloading by means of heart assist devices (LVADs). Methods: Myocardial tissue was obtained from 10 patients with end-stage cardiomyopathy at the time of LVAD implantation (pre-LVAD) and following orthotopic heart transplantation (post-LAVD). In addition, biopsies of 4 normal hearts served as a control group. Paraffin embedded sections were dual stained for cathepsin g and tryptase, a known marker for mast cells, using standard immunohistochemistry protocols. Total cathepsin g positive (pos.) mast cells were counted. Results: No cathepsin g pos. MCs were found in normal hearts. However, we found evidence for cathepsin g in cardiac MCs in heart failure tissues (Pre-LVAD). During heart failure 46% of total MCs were cathepsin g pos. as compared to after mechanical unloading where only 11% of total MCs were cathepsin g pos. (p<0.001). Conclusion: Heart failure causes an increase of myocardial MCs. Cathepsin g pos. MC accumulate during heart failure and their total percentage decreases after ventricular unloading. This coincides with the decrease in myocyte necrosis, hypertrophy and fibrosis. Thus, cathepsin g may play a role in the progression to heart failure by activating angiotensin II