Survival, differentiation, and migration of bioreactor-expanded human neural precursor cells in a model of Parkinson disease in rats.

OBJECT: Fetal tissue transplantation for Parkinson disease (PD) has demonstrated promising results in experimental and clinical studies. However, the widespread clinical application of this therapeutic approach is limited by a lack of fetal tissue. Human neural precursor cells (HNPCs) are attractive candidates for transplantation because of their long-term proliferation activity. Furthermore, these cells can be reproducibly expanded in a standardized fashion in suspension bioreactors. In this study the authors sought to determine whether the survival, differentiation, and migration of HNPCs after transplantation depended on the region of precursor cell origin, intracerebral site of transplantation, and duration of their expansion. METHODS: Human neural precursor cells were isolated from the telencephalon, brainstem, ventral mesencephalon, and spinal cord of human fetuses 8-10 weeks of gestational age, and their differentiation potential characterized in vitro. After expansion in suspension bioreactors, the HNPCs were transplanted into the striatum and substantia nigra of parkinsonian rats. Histological analyses were performed 7 weeks posttransplantation. RESULTS: The HNPCs isolated from various regions of the neuraxis demonstrated diverse propensities to differentiate into astrocytes and neurons and could all successfully expand under standardized conditions in suspension bioreactors. At 7 weeks posttransplantation, survival and migration were significantly greater for HNPCs obtained from the more rostral brain regions. The HNPCs differentiated predominantly into astrocytes after transplantation into the striatum or substantia nigra regions, and thus no behavioral improvement was observed. CONCLUSIONS: Understanding the regional differences in HNPC properties is prerequisite to their application for PD cell restoration strategies.

Graft Utilization in the Bridging Reconstruction of Irreparable Rotator Cuff Tears: A Systematic Review.

BACKGROUND: Rotator cuff tears are one of the most common conditions affecting the shoulder. Because of the difficulty in managing massive rotator cuff tears and the inability of standard techniques to prevent arthropathy, surgeons have developed several novel techniques to improve outcomes and ideally alter the natural history. PURPOSE: To systematically review the existing literature and analyze reported outcomes to evaluate the effectiveness of using a bridging graft reconstruction technique to treat large to massive irreparable rotator cuff tears. STUDY DESIGN: Systematic review. METHODS: A systematic search of PubMed, EMBASE, CINAHL, and CENTRAL was employed with the key terms "tear," "allograft," and "rotator cuff." Eligibility was determined by a 3-phase screening process according to the outlined inclusion/exclusion criteria. Data in relation to the primary and secondary outcomes were summarized. The results were synthesized according to the origin of the graft and the level of evidence. RESULTS: Fifteen studies in total were included in this review: 2 comparative studies and 13 observational case series. Both the biceps tendon and the fascia lata autograft groups had significantly superior structural integrity rates on magnetic resonance imaging at 12-month minimum follow-up when compared with their partial primary repair counterparts (58% vs 26%, P = .036; 79% vs 58%, P < .05), respectively. Multiple noncomparative case series investigating allografts, xenografts, and synthetic materials for bridging reconstruction of large to massive rotator cuff tears demonstrated high structural healing rates (74%-90%, 73%-100%, and 60%-90%, respectively). Additionally, both comparative studies and case series demonstrated a general improvement of patients' functional outcome scores. CONCLUSION: Using a graft for an anatomic bridging rotator cuff repair results in improved function on objective testing and may be functionally better than nonanatomic or partial repair of large to massive rotator cuff tears. Allograft or xenograft techniques appear to be favorable options, given demonstrated functional improvement, imaging-supported graft survival, and lack of harvest complication risk. More high-quality randomized controlled studies are needed to further assess this technique.

Reconstruction of Focal Femoral Head Cartilage Defects With a Chitin-Based Scaffold.

It is well known that articular cartilage defects have little capability to heal. For grade III or IV cartilage defects, surgical intervention may be required for symptomatic patients. Microfracture is a commonly used surgical technique to address these injuries. However, microfracture has drawbacks, which include the risk of ossification of the newly formed tissue, as well as the imperfect and fragile nature of the fibrous cartilage. Given the challenges associated with microfracture, BST-CarGel (Piramal Healthcare, Laval, Quebec, Canada) has been developed to stabilize and support the nascent clot. This chitin-based polymer is mixed with the patient's own blood and inserted onto the microfractured defect. The polymer allows normal clot formation and provides a matrix to strengthen the clot, prevent retraction, and increase its adhesiveness to the natural tissue. We present, with a video example, a detailed arthroscopic technique for using BST-CarGel to fill a focal femoral head cartilage defect.

Graft Utilization in the Augmentation of Large-to-Massive Rotator Cuff Repairs: A Systematic Review.

BACKGROUND: Current treatment options for symptomatic large-to-massive rotator cuff tears can reduce pain, but failure rates remain high. Surgeons have incorporated synthetic and biologic grafts to augment these repairs, with promising results. Multiple reviews exist that summarize these products; however, no systematic review has investigated the grafts' ability to maintain structural integrity after augmentation of large-to-massive rotator cuff repairs. PURPOSE: To systematically review and evaluate the effectiveness of grafts in the augmentation of large-to-massive rotator cuff repairs. STUDY DESIGN: Systematic review. METHODS: A comprehensive search of 4 reputable databases was completed. Inclusion criteria were (1) large-to-massive rotator cuff tear, (2) graft augmentation of primary repairs ± primary repair control group, and (3) minimum clinical and radiologic follow-up of 12 months. Two reviewers screened the titles, abstracts, and full articles and extracted the data from eligible studies. Results were summarized into evidence tables stratified by graft origin and level of evidence. RESULTS: Ten studies fit the inclusion criteria. Allograft augmentation was functionally and structurally superior to primary repair controls, with intact repairs in 85% versus 40% of patients (P < .01). This was supported by observational study data. Xenograft augmentation failed to demonstrate superiority to primary repair controls, with worse structural healing rates (27% vs 60%; P =.11). Both comparative studies supported this finding. There have also been many reports of inflammatory reactions with xenograft use. Polypropylene patches are associated with improved structural (83% vs 59% and 49%; P < .01) and functional outcomes when compared with controls and xenograft augmentation; however, randomized data are lacking. CONCLUSION: Augmentation of large-to-massive rotator cuff repairs with human dermal allografts is associated with superior functional and structural outcome when compared with conventional primary repair. Xenograft augmentation failed to demonstrate a statistically significant difference and may be associated with worse rerupture rates and occasional severe inflammatory reactions. Polypropylene patches have initial promising results. Research in this field is limited; future researchers should continue to develop prospective, randomized controlled trials to establish clear recommendations.

Lateral Decubitus All-Arthroscopic Latarjet Procedure for Treatment of Shoulder Instability.

Shoulder instability can be a challenging condition to treat when it becomes refractory to soft-tissue procedures or when bone loss exceeds 25% to 27% of the glenoid. The Bristow-Latarjet procedure has been developed and popularized to deal with these concerns. Traditionally, the procedure has been performed as an open approach; however, this has been recently supplanted by novel arthroscopic techniques. We present a technique for the procedure performed with the patient in a semi-lateral decubitus position that assists with optimal graft placement on the native glenoid. We use the cannulated Bristow-Latarjet Instability Shoulder System (DePuy Mitek, Raynham, MA). After a diagnostic arthroscopic evaluation, we use multiple arthroscopic anterior portals to debride the rim of the glenoid. The coracoid is prepared and taken down arthroscopically, and the cannulated guide is attached and advanced through an arthroscopically created subscapularis split. With the shoulder held in a reduced position, we are then able to drill and anchor the graft to the native glenoid. The patient is able to begin gentle range-of-motion exercises immediately postoperatively.

Functional improvement with low-dose dopaminergic grafts in hemiparkinsonian rats.

OBJECTIVE: The beneficial functional effects of neural transplantation in Parkinson's disease are often directly attributed to the number of surviving dopaminergic cells within a graft. However, recent clinical trials of fetal neural transplantation suggest that a high number of dopaminergic cells may induce serious side effects. In this study, we explored the ability of low-dose dopaminergic grafts to produce functional benefits in the 6-hydroxydopamine rodent model of Parkinson's disease over a long period of observation. METHODS: Twelve rats received either 50,000 or 400,000 fetal ventral mesencephalic cells implanted into the striatum. Rotational behavior was assessed after the lesion and at 3, 6, 9, and 12 weeks after transplantation. Twelve weeks after transplantation, animals were perfused, and microtome sections were stained for tyrosine hydroxylase, glial fibrillary acidic protein, heat-shock protein 27, and vimentin. RESULTS: The low-dose group had a three-fold increase in tyrosine hydroxylase-positive cell survival rate compared with the high-dose group rate. The low-dose group also had a mean cell diameter significantly higher than the high-dose group. There was no significant difference between groups in fiber density; however, a higher percentage of longer fibers was encountered in the low-dose group. The low-dose group had a lower degree of trauma in the striatum, as assessed by optical density scores from glial fibrillary acidic protein, heat-shock protein 27, and vimentin staining. There was significant improvement in rotational behavior in the high-dose group at 3 weeks after transplantation, whereas the rotational behavior normalized in the low-dose group at 6 weeks after grafting. There was no significant difference in rotational behavior scores between groups at 6 weeks after grafting. CONCLUSION: This study demonstrates that over time, a low-dose dopaminergic graft has the capability of eliciting the same functional effect as a high-dose graft. Furthermore, low-dose grafts may increase graft survival, fiber outgrowth, and dopamine production and decrease trauma to the brain.