hMSCs survive in the porcine disc for at least 6 months and express typical chondrocyte markers suggesting differentiation toward disc-like cells. As in autologous animal models the combination with a three-dimensional-hydrogel carrier seems to facilitate differentiation and survival of MSCs in the disc. Xenotransplantation seems to be valuable in evaluating the possibility for human cell therapy treatment for intervertebral discs.

Background:The syndrome angina pectoris with effort-related chest pain or discomfort is usually easy to recognize. However, vague and nonspecific symptoms may cause little reason for extensive evaluation. The prognosis of such patients in the general population has so far not been well described.Hypothesis: The study was undertaken to investigate longterm prognosis in men with chest pain considered to be nonspecific in comparison with men with typical angina pectoris (AP) or prior myocardial infarction (MI), and men without chest pain.Methods: At the second screening of the Goteborg Primary Prevention Study in [1974][1975][1976][1977]6,488 men aged 51 to 59 years at baseline were available for the present analysis. Men who had responded positively to a postal questionnaire about chest pain during exercise or at rest were interviewed by a physician according to a Rose questionnaire at the screening examination. Those with typical or probable AP were further examined by a single experienced physician. The following four groups were formed: Group 1: men who did not complain of chest pain (n = 5,545). Group 2: men who had not consulted any doctor because of chest pain, but who had chest pain according to a questionnaire (n = 441); these men were not considered to have AP according to a three-step examination by expenenced physicians. Group 3: typical AP (n = 232).Group 4: men who had suffered an MI (n = 134). Results: During 16 years of follow-up, coronary heart disease (CHD) mortality forGroups 1 4 was 8.0,19.5,24.8, and 48.5%, respectively. Mortality from all cardiovascular diseases was 1 1.5,24.5,3 1.2, and 59.0% respectively. Noncardiovasculardisease mortality was 14.1,17.7,14.3, and 8.7%, respectively. Thus, the relative risk (RR) for CHD mortality among men with nonspecific chest pain (Group 2) was 2.77 [95% confidence interval (CI) 2.20,3.50], for all cardiovascular disease mortality 2.46 (95% CI 2.00,3.02), and for noncardiovascular disease mortality I .60 (95% CI 1.28, 2.00). Total mortality in this group was as high (44%) as among those with typical AP (45%), but the highest mortality was found among men with a previous MI (68%). In men without chest pain it was 26%. Patients of Groups 2 4 had higher levels of cardiovascular risk factors than those in Group 1. Neither any specific questions in the Rose questionnaire, nor electrocardiographic changes at rest (uncommon) were of prognostic significance. Serum cholesterol, systolic blood pressure, diabetes, and smoking were significant predictors of outcome, both with respect to fatal CHD and to total mortality during the 16-year follow-up. Conclusion:We found a high cardiovascular as well as noncardiovascular mortality among patients with chest pain who had not been considered to have AP at a three-step examination procedure. It is important to be suspicious of early CHD symptoms in men (and women?) with "nonspecific" chest symptoms and to analyze their cardiovascular risk factor pattern further because they are at considerably higher risk for future events t...

Abstract. Rosengren A, Wilhelmsen L, Hagman M, Wedel H (Östra University Hospital, Göteborg; Kungälv Hospital, Kungälv; and Nordic School of Public Health, Göteborg, Sweden). Natural history of myocardial infarction and angina pectoris in a general population sample of middle-aged men: a 16-year follow-up of the Primary Prevention Study, Göteborg, Sweden. J Intern Med 1998; 244: 495᎐505.Objectives. Although many studies have described prognosis in patients with coronary heart disease (CHD), few have compared outcome in men with clinical evidence of CHD with healthy men from the general population over an extended follow-up. This study aimed to compare long-term prognosis in men with a history of myocardial infarction (MI) and in men with angina pectoris (AP) without MI, with men without clinical signs of CHD. Design. Longitudinal general population study. Setting. City of Göteborg, Sweden. Subjects. From a general population sample, 195 men who had survived an MI for 0᎐19 years (median 3 years) and 314 men with AP but no MI (uncomplicated AP) at baseline in 1974᎐77 were identified and compared with 6591 men without clinical coronary disease. All were aged 51᎐59 years. Incident non-fatal and fatal cases occurring until the beginning of 1983 were also followed (n ϭ 317). Main outcome measures.Death from CHD, from other causes and from all causes during a follow-up of at least 16 years. Results. Overall survival was 72% amongst men without coronary disease, 53% amongst men with uncomplicated AP and 34% amongst men with past MI at baseline. In survivors of MI the risk-factoradjusted relative risk (RR) of coronary death during follow-up was 6.67 (95% confidence interval (CI) 5.29᎐8.39), of dying from non-cardiovascular causes 1.35 (0.96᎐1.91), and of dying from any cause 3.20 (2.67᎐3.83). During the first 4 years after the baseline examination, the adjusted RR of CHD death was 15.96 (10.29᎐24.74), and of dying from any cause 5.22 (3.68᎐7.41). During the last 4 years of follow-up, relative risk was still 5.87 (3.44᎐10.01) for CHD death and 2.93 (2.05᎐4.18) for death from any cause. In men with uncomplicated AP, the adjusted relative risk of CHD death during the first 4 years was 4.05 (2.27᎐7.22) and 3.23 (2.10᎐4.96) during the last 4-year period. After the first year, the incident MI cases had the same average annual mortality (about 5%) as the prevalent cases. Conclusions. In survivors of MI, mortality risk remained high even after an extended follow-up. Men with angina had a better prognosis, but still a compromised survival compared with the general population.

Transplantation of mesenchymal stem cells (MSCs) has been suggested for disk degeneration, which is characterized by dysfunctional cells and low proteoglycan production. The aim of this study was to examine the effects of a 3D co-culture system using human disk cells (DCs) and MSCs on collagen and proteoglycan production. DCs and MSCs were expanded in monolayer and grown in pellet cultures for 7, 14 and 28 days and analyzed for hydroxyproline (HP), reflecting total collagen production, and glycosaminoglycan (GAG) accumulation. DCs and MSCs co-cultured at different ratios (25/75, 50/50 and 75%/25%) were examined for GAG accumulation. Collagen type II expression was analyzed immunohistochemically. In a second series, conditioned media were added to pellet cultures of degenerated DCs or MSCs. DCs from degenerated disks and MSCs demonstrated lower total collagen production than non-degenerated DC pellets. GAG production was comparable in DCs and MSCs, except in the youngest donor, with MSC producing about 10 times higher GAG/DNA. Co-cultures resulted in approximately 1.5 times higher GAG/DNA production than DCs. Increased collagen type II expression was seen in co-cultures compared to DC or MSC culture alone, except in the case with highly active MSCs. No positive effect of conditioned media was seen. In conclusion, co-culture of MSCs with degenerated DCs increased proteoglycan and collagen-type ceII production, indicating that in future clinical therapy MSCs can be transplanted without pre-differentiation in vitro. The lack of effect of conditioned media suggests that the positive effect of co-culture on matrix production is not due to soluble factors.

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