Cardiovascular disease in pregnancy: Prevalence and obstetric outcomes in a Swedish population-based cohort study between 2000 and 2019.

INTRODUCTION: The prevalence of cardiovascular disease during pregnancy (cardiovascular disease diagnosed before, during or up to 6 months after childbirth) and the risk of adverse outcomes associated with it have not been previously described in Sweden. This study examined trends in prevalence of cardiovascular disease and its association with maternal and perinatal outcomes, overall and by timing of diagnosis in relation to pregnancy. MATERIAL AND METHODS: This population-based observational retrospective cohort study consisted of women aged 15-49 years who were registered in the Swedish Medical Birth Register 2000-2019. Prevalence was defined as annual diagnosis of cardiovascular disease per pregnant woman as numerator and all pregnant women per year as denominator. Adverse maternal and perinatal outcomes were analyzed using time-dependent Cox regression and Poisson regression models. Outcomes were obtained during and after childbirth up to 1 year postpartum, depending on the outcome. RESULTS: There were 2 069 107 births to 1 186 137 women (911 101 primiparous). The prevalence of cardiovascular disease among pregnant women in Sweden during 2000-2019 increased from 0.31% to 1.34%, for non-congenital cardiovascular disease, this was primarily driven by arrythmia (0.11%-0.58%). Primiparous women with cardiovascular disease had a higher risk of eclampsia over-all (aHR 4.50, 95% CI 2.01-10.05) and when diagnosed during pregnancy (aHR 3.22, 95% CI 1.21-8.61); admission to psychiatric ward overall (aHR 2.51, 95% CI 1.30-4.83), and when diagnosed during pregnancy (aHR 2.54, 95% CI 1.21-5.34); and one-year mortality when diagnosed before pregnancy (aHR 1.67, 95% CI 1.16-2.42) and when diagnosed postpartum (aHR 6.59, 95% CI 3.38-12.84), compared to those without cardiovascular disease. Children born to women with cardiovascular disease diagnosed both overall and in relation to timing of diagnosis had an increased risk of being born preterm and small for gestational age. CONCLUSIONS: Cardiovascular disease prevalence among pregnant women in Sweden increased during 2000-2019, primarily driven by arrhythmias. In primiparous women, the timing of diagnosis of cardiovascular disease is important for maternal and perinatal outcomes, including when diagnosed postpartum. This calls for awareness among all staff when planning pregnancy and monitoring women with cardiovascular disease throughout pregnancy and in the postpartum period.

Heart disease in pregnancy and risk of pre-eclampsia: a Swedish register-based study.

BACKGROUND AND AIMS: Pre-eclampsia complicates 3-5% of pregnancies worldwide and is associated with adverse outcomes for the mother and the offspring. Pre-eclampsia and heart failure have common risk factors, including hypertension, obesity and diabetes. It is not known whether heart failure increases the risk of pre-eclampsia. This study examines whether pregestational heart failure increases the risk of pre-eclampsia. METHODS: In a registry-based case-cohort study that included all pregnancies in Sweden (n=3 125 527) between 1990 and 2019, all pregnancies with pre-eclampsia (n=90 354) were identified and up to five control pregnancies (n=451 466) for each case were chosen, matched on the mother's birth year. Multiple logistic regression analysis was used to evaluate the impact of heart failure on the risk of pre-eclampsia, with adjustment for established risk factors and other cardiovascular diseases. RESULTS: Women with heart failure had no increased risk for pre-eclampsia, OR 1.02 (95% CI 0.69 to 1.50). Women with valvular heart disease had an increased OR of preterm pre-eclampsia, with an adjusted OR of 1.78 (95% CI 1.04 to 3.06). Hypertension and diabetes were independent risk factors for pre-eclampsia. Obesity, multifetal pregnancies, in vitro fertilisation, older age, Nordic origin and nulliparity were more common among women who developed pre-eclampsia compared with controls. CONCLUSION: Women with heart failure do not have an increased risk of pre-eclampsia. However, women with valvular heart disease prior to pregnancy have an increased risk of developing preterm pre-eclampsia independent of other known risk factors.

Early suppression policies protected pregnant women from COVID-19 in 2020: A population-based surveillance from the Nordic countries.

INTRODUCTION: The Coronavirus 2019 Disease (COVID-19) pandemic reached the Nordic countries in March 2020. Public health interventions to limit viral transmission varied across different countries both in timing and in magnitude. Interventions indicated by an Oxford Stringency Index ≥50 were implemented early (March 13-17, 2020) in Denmark, Finland, Norway and Iceland, and on March 26, 2020 in Sweden. The aim of the current study was to assess the incidence of COVID-19-related admissions of pregnant women in the Nordic countries in relation to the different national public health strategies during the first year of the pandemic. MATERIAL AND METHODS: This is a meta-analysis of population-based cohort studies in the five Nordic countries with national or regional surveillance in the Nordic Obstetric Surveillance System (NOSS) collaboration: national data from Denmark, Finland, Iceland and Norway, and regional data covering 31% of births in Sweden. The source population consisted of women giving birth in the included areas March 1-December 31, 2020. Pregnant women with a positive SARS-CoV-2 PCR test ≤14 days before hospital admission were included, and admissions were stratified as either COVID-19-related or non-COVID (other obstetric healthcare). Information about public health policies was retrieved retrospectively. RESULTS: In total, 392 382 maternities were considered. Of these, 600 women were diagnosed with SARS-CoV-2 infection and 137 (22.8%) were admitted for COVID-19 symptoms. The pooled incidence of COVID-19 admissions per 1000 maternities was 0.5 (95% confidence interval [CI] 0.2 to 1.2, I2 = 77.6, tau2 = 0.68, P = 0.0), ranging from no admissions in Iceland to 1.9 admissions in the Swedish regions. Interventions to restrict viral transmission were less stringent in Sweden than in the other Nordic countries. CONCLUSIONS: There was a clear variation in pregnant women's risk of COVID-19 admission across countries with similar healthcare systems but different public health interventions to limit viral transmission. The meta-analysis indicates that early suppression policies protected pregnant women from severe COVID-19 disease prior to the availability of individual protection with vaccines.

Risk of uterine rupture in multiparous women after induction of labor with prostaglandin: A national population-based cohort study.

OBJECTIVE: To assess whether, after induction of labor with prostaglandin, multiparous (≥2 para) women have an increased risk of uterine rupture compared with nulliparous or uniparous women. METHODS: This was a retrospective population-based cohort study including women who underwent induction with prostaglandin in all maternity wards in Sweden between May 1996 and December 2019 (n = 56 784). The study cohort was obtained by using data from the Swedish Medical Birth Register, which contains information from maternity and delivery records. The main outcome measure was uterine rupture. RESULTS: Overall, multiparous women induced with prostaglandin had an increased risk of uterine rupture compared with nulliparous women (adjusted odds ratio [OR], 3.33 [95% confidence interval (CI), 1.38-8.04]; P < 0.007). Multiparous women with no previous cesarean section (CS) induced with prostaglandin had more than three times higher risk of uterine rupture (crude OR, 3.55 [95% Cl, 1.48-8.53]; P = 0.005) compared with nulliparous women and four times higher risk compared with uniparous women (OR, 4.10 [95% CI, 1.12-15.00]; P < 0.033). Multiparous women with previous CS had a decreased risk of uterine rupture compared with uniparous women with one previous CS (crude OR, 0.41 [95% Cl, 0.21-0.78]; P = 0.007). CONCLUSION: Our study implies that multiparity in women with no previous CS is a risk factor for uterine rupture when induced with prostaglandin. This should be taken into consideration when deciding on the appropriate method of induction.

Variations across Europe in hospitalization and management of pregnant women with SARS-CoV-2 during the initial phase of the pandemic: Multi-national population-based cohort study using the International Network of Obstetric Survey Systems (INOSS).

INTRODUCTION: The majority of data on COVID-19 in pregnancy are not from sound population-based active surveillance systems. MATERIAL AND METHODS: We conducted a multi-national study of population-based national or regional prospective cohorts using standardized definitions within the International Network of Obstetric Survey systems (INOSS). From a source population of women giving birth between March 1 and August 31, 2020, we included pregnant women admitted to hospital with a positive SARS-CoV-2 PCR test ≤7 days prior to or during admission and up to 2 days after birth. The admissions were further categorized as COVID-19-related or non-COVID-19-related. The primary outcome of interest was incidence of COVID-19-related hospital admission. Secondary outcomes included severe maternal disease (ICU admission and mechanical ventilation) and COVID-19-directed medical treatment. RESULTS: In a source population of 816 628 maternities, a total of 2338 pregnant women were admitted with SARS-CoV-2; among them 940 (40%) were COVID-19-related admissions. The pooled incidence estimate for COVID-19-related admission was 0.59 (95% confidence interval 0.27-1.02) per 1000 maternities, with notable heterogeneity across countries (I2 = 97.3%, P = 0.00). In the COVID-19 admission group, between 8% and 17% of the women were admitted to intensive care, and 5%-13% needed mechanical ventilation. Thromboprophylaxis was the most frequent treatment given during COVID-19-related admission (range 14%-55%). Among 908 infants born to women in the COVID-19-related admission group, 5 (0.6%) stillbirths were reported. CONCLUSIONS: During the initial months of the pandemic, we found substantial variations in incidence of COVID-19-related admissions in nine European countries. Few pregnant women received COVID-19-directed medical treatment. Several barriers to rapid surveillance were identified. Investment in robust surveillance should be prioritized to prepare for future pandemics.

Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.

Importance: Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown. Objective: To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening. Design, Setting, and Participants: Cross-sectional study of a population-based cohort of women in Sweden (n = 10 528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected. Exposures: Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures. Main Outcomes and Measures: Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100. Results: A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk. Conclusions and Relevance: Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.

Placenta accreta spectrum-A single-center retrospective observational cohort study of multidisciplinary management over time.

OBJECTIVE: To evaluate whether the results of a previous study that showed a decrease in blood loss and transfusions with a multidisciplinary approach, including a fixed team when delivering women diagnosed with placenta accreta spectrum at Sahlgrenska University Hospital, remained low throughout time, and to investigate hospital stay and maternal and neonatal complications during a time period with varying team structure compared with previous periods. METHODS: A retrospective observational cohort study comparing data from medical records including three cohorts of women diagnosed with placenta accreta spectrum between October 2003 and December 2020. Cohort 1 consisted of women delivered before the multidisciplinary approach was introduced. Cohort 2 and cohort 3 were both managed in a multidisciplinary manner, but while cohort 2 was managed by a fixed team, cohort 3 was managed by several different senior specialists. The data were analyzed using Kruskal-Wallis test. RESULTS: Blood loss and need for transfusion were significantly lower for cohort 3 and cohort 2 compared with cohort 1. No significant difference was found between cohort 3 and cohort 2. CONCLUSION: The multidisciplinary management and surgical method employed at Sahlgrenska University Hospital have lowered blood loss and the need for transfusions, even over time.

Prenatal detection of placenta previa and placenta accreta spectrum: Evaluation of the routine mid-pregnancy obstetric ultrasound screening between 2013 and 2017.

OBJECTIVE: To examine the detection rate of placenta previa and placenta accreta spectrum (PAS) by routine mid-pregnancy obstetric ultrasound and to estimate risk factors and prevalence within this cohort. METHODS: This was an observational cohort study with prospectively collected data. Women attending routine mid-pregnancy obstetric ultrasound at the Sahlgrenska University Hospital with a suspected cup-shaped placenta (cohort 1, n = 339) and women diagnosed with placenta previa or PAS (cohort 2, n = 227) were analyzed according to detection rate, risk factors, and prevalence. RESULTS: The detection rates of placenta previa and PAS were 49% (98) and 25% (14), respectively. However, 216 (99%) women with placenta previa were diagnosed prenatally, as were 14 (50%) women with PAS. In vitro fertilization was identified as the strongest independent risk factor for placenta previa (odds ratio 6.96; 95% confidence interval 4.77-10.16, P < 0.001). Risk factors were present for all women with PAS. The prevalence of placenta previa was 44/10 000 deliveries, and for PAS, 5.6/10 000 deliveries. CONCLUSION: The existing routine mid-pregnancy obstetric ultrasound screening showed low detection rate for placenta previa and PAS. Adding risk factors could improve the detection rate.

Study protocol: establishment of a multicentre pre-eclampsia database and biobank in Sweden: GO PROVE and UP MOST, a prospective cohort study.

INTRODUCTION: Pre-eclampsia, a multisystem disorder in pregnancy, is one of the most common causes of maternal morbidity and mortality worldwide. However, we lack methods for objective assessment of organ function in pre-eclampsia and predictors of organ impairment during and after pre-eclampsia. The women's and their partners' experiences of pre-eclampsia have not been studied in detail. To phenotype different subtypes of the disorder is of importance for prediction, prevention, surveillance, treatment and follow-up of pre-eclampsia.The aim of this study is to set up a multicentre database and biobank for pre-eclampsia in order to contribute to a safer and more individualised treatment and care. METHODS AND ANALYSIS: This is a multicentre cohort study. Prospectively recruited pregnant women ≥18 years, diagnosed with pre-eclampsia presenting at Sahlgrenska University Hospital, Uppsala University Hospital and at Södra Älvsborgs Hospital, Sweden, as well as normotensive controls are eligible for participation. At inclusion and at 1-year follow-up, the participants donate biosamples that are stored in a biobank and they are also asked to participate in various organ-specific evaluations. In addition, questionnaires and interviews regarding the women's and partner's experiences are distributed at follow-up. ETHICS AND DISSEMINATION: By creating a database and biobank, we will provide the means to explore the disorder in a broader sense and allow clinical and laboratory discoveries that can be translated to clinical trials aiming at improved care of women with pre-eclampsia. Further, to evaluate experiences and the psychological impact of being affected by pre-eclampsia can improve the care of pregnant women and their partners. In case of incidental pathological findings during examinations performed, they will be handled in accordance with clinical routine. Data are stored in a secure online database. Biobank samples are identified through the women's personal identification number and pseudonymised after identification in the biobank before analysis.This study was approved by the regional ethical review board in Gothenburg on 28 December 2018 (approval number 955-18) and by the Swedish Ethical Review Authority on 27 February 2019 (approval number 2019-00309).Results from the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN13060768.

COVID-19 in pregnancy-characteristics and outcomes of pregnant women admitted to hospital because of SARS-CoV-2 infection in the Nordic countries.

INTRODUCTION: Population-based studies about the consequences of SARS-CoV-2 infection (COVID-19) in pregnancy are few and have limited generalizability to the Nordic population and healthcare systems. MATERIAL AND METHODS: This study examines pregnant women with COVID-19 in the five Nordic countries. Pregnant women were included if they were admitted to hospital between 1 March and 30 June 2020 and had a positive SARS-CoV-2 PCR test ≤14 days prior to admission. Cause of admission was classified as obstetric or COVID-19-related. RESULTS: In the study areas, 214 pregnant women with a positive test were admitted to hospital, of which 56 women required hospital care due to COVID-19. The risk of admission due to COVID-19 was 0.4/1000 deliveries in Denmark, Finland and Norway, and 3.8/1000 deliveries in the Swedish regions. Women hospitalized because of COVID-19 were more frequently obese (p < 0.001) and had a migrant background (p < 0.001) compared with the total population of women who delivered in 2018. Twelve women (21.4%) needed intensive care. Among the 56 women admitted due to COVID-19, 48 women delivered 51 infants. Preterm delivery (n = 12, 25%, p < 0.001) and cesarean delivery (n = 21, 43.8%, p < 0.001) were more frequent in women with COVID-19 compared with women who delivered in 2018. No maternal deaths, stillbirths or neonatal deaths were reported. CONCLUSIONS: The risk of admission due to COVID-19 disease in pregnancy was low in the Nordic countries. A fifth of the women required intensive care and we observed higher rates of preterm and cesarean deliveries. National public health policies appear to have had an impact on the risk of admission due to severe COVID-19 disease in pregnancy. Nordic collaboration is important in collecting robust data and assessing rare outcomes.

Lessons learnt from anonymized review of cases of peripartum hysterectomy by international experts: A qualitative pilot study.

Severe obstetric complications are not extensively studied and individual cases are used too little and inappropriately in quality improvement activities, due to limited numbers and prioritization of quantitative research. Nordic and European experts performed a qualitative pilot study using anonymized cases of peripartum hysterectomy. It was feasible to anonymize narratives and we learned lessons in the form of themes for improved clinical care and future research. Therefore, we plan a Nordic anonymized review of the care of women who have undergone peripartum hysterectomy based on narratives. The qualitative outcomes of clinically relevant themes for quality improvement and research will add value to the quantitative analyses from the Nordic medical birth registries. In the longer term, we believe that qualitative audits should be an essential part of the process of continuing improvement in maternity care.

Sociodemographic disparities in stage-specific incidences of endometrial cancer: a registry-based study in West Sweden, 1995-2016.

Background: For a few types of cancer, lower socioeconomic status (SES) is associated with higher incidence, and for even more cancer types it is associated with having a less favorable tumor stage at diagnosis. For endometrial cancer (EC), however, there is no clear evidence of such associations with SES. There is a need for analysis of sociodemographic disparities in EC incidences according to stage at diagnosis, which may provide support for trying to improve early detection of EC. Material and methods: Stage-specific incidences of endometrioid and non-endometrioid endometrial carcinomas [EECs (∼90% of all EC cases) and NECs (∼10%)] were analyzed for the population of the Western Swedish Healthcare Region, taking into account year (1995-2016), age, educational level (low, intermediate and high), and immigrant status (Swedish-born, foreign-born). All EC cases were identified and data were obtained from population-based registries. Results: Stage distribution of diagnosed EECs differed significantly according to the educational level of patients who were aged between 50 and 74 years at diagnosis, but not in the case of younger or older patients. An analysis based on 3113 EEC cases aged 50-74 years at diagnosis revealed marked disparities in the stage-II to stage-IV EEC incidences but not in the stage-I EEC incidence. Compared to women with a high level of education, the incidence rate ratios of stage-I, stage-II and stage-III and -IV EEC in women with a low level of education were 1.00 (95% CI: 0.90-1.12), 1.65 (1.13-2.42), and 1.82 (1.33-2.49), respectively. For NEC, we found no such association. Conclusions: Elevated incidences of stage-II to stage-IV EEC in 50- to 74-year-old women with a low level of education suggest that there should be targeted health service trials aimed at improving awareness of EC. Well-targeted EC awareness programs might lead to considerable health benefits.

DNA ploidy status, S-phase fraction, and p53 are not independent prognostic factors for survival in endometrioid endometrial carcinoma FIGO stage I-III.

OBJECTIVES: To assess the effects on relative survival of established and new prognostic factors in stage I-III grade 1-3 endometrioid endometrial carcinoma and in the subgroup of stage I grade 1-2. METHODS: This was a population-based, retrospective study including all women (n=1113) in the western Swedish healthcare region diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I-III grade 1-3 endometrioid endometrial carcinoma in 2006-2011. Histology, grade, stage, and age were prospectively reported to the regional clinical and national cancer registers. DNA ploidy and S-phase fraction were analyzed by flow cytometer. S-phase fraction cut-off was set at ≥8%. Tumor biopsies were classified as diploid if there was one G0/G1 peak or the DNA index was 1.0±0.04. Overexpression of p53 as determined by immunohistochemistry was positive if strong nuclear staining was found in >30% of the neoplastic cells. RESULTS: Based on univariable statistical analyses we found that 5-year relative survival was significantly associated with S-phase fraction, DNA ploidy, p53, stage, grade, and age. Excess mortality for S-phase fraction ≥8%, aneuploidy, and p53 overexpression was 8, 14, and 8 and times higher, respectively. However, in a multivariable regression model, adjusted for stage, grade, and age, S-phase fraction, DNA ploidy, and p53 were not statistically independent prognostic factors (p=0.413, p=0.107, p=0.208, respectively) for 5-year relative survival in stage I-III grade 1-3 endometrioid endometrial carcinoma. In a subgroup analysis of stage I grade 1-2, aneuploidy identified a subgroup with impaired 5-year relative survival. CONCLUSION: We can conclude that S-phase fraction, DNA ploidy, and p53 overexpression did not improve identification of high-risk patients by stage, grade, and age in stage I-III endometrioid endometrial carcinoma. In stage I, aneuploidy and grade 2 predicted lower relative survival rates than other variables.

Population-based cohort study of the effect of endometrial cancer classification and treatment criteria on long-term survival.

OBJECTIVE: To evaluate if increased individualization in endometrial cancer classification/treatment affected relative survival. METHODS: The present retrospective register-based population study included data from all women in the western Swedish healthcare region who were treated for endometrial cancer between January 1, 1995, and December 31, 2011. Outcomes and prognostic data were retrieved from the western Swedish healthcare region's cancer and clinical endometrial cancer registries. Patients were stratified based on two different treatment programs (cohort 1 January 1, 1995, to September 10, 2006, and cohort 2 September 11, 2006, to December 31, 2011) and relative survival was compared. RESULTS: Data from 4338 patients were included; 2936 in cohort 1 and 1402 in cohort 2. Among endometrioid endometrial carcinomas, the 5-year relative survival rate for did not differ significantly between the groups (P=0.751); radiotherapy was used more frequently in cohort 1 (P<0.001). Among non-endometrioid endometrial carcinomas, relative survival was lower in cohort 1 (P=0.006); radiotherapy use was more frequent in cohort 1 and chemotherapy use was more frequent in cohort 2 (P=0.001). CONCLUSION: Increased individualization in endometrioid endometrial cancer management did not improve relative survival. Improved relative survival was observed for non-endometrioid endometrial cancer; possibly due to increased adjuvant chemotherapy use. This article is protected by copyright. All rights reserved.

Transplantation of human mesenchymal stems cells into intervertebral discs in a xenogeneic porcine model.

STUDY DESIGN: Experimental and descriptive study of a xenotransplantation model in minipigs. OBJECTIVE: To study survival and function of human mesenchymal stem cells (hMSCs) after transplantation into injured porcine spinal discs, as a model for cell therapy. SUMMARY OF BACKGROUND DATA: Biologic treatment options of the intervertebral disc are suggested for patients with chronic low back pain caused by disc degeneration. METHODS: Three lumbar discs in each of 9 minipigs were injured by aspiration of the nucleus pulposus (NP), 2 weeks later hMSCs were injected in F12 media suspension (cell/med) or with a hydrogel carrier (Puramatrix) (cell/gel). The animals were sacrificed after 1, 3, or 6 months. Disc appearance was visualized by magnetic resonance imaging. Immunohistochemistry methods were used to detect hMSCs by antihuman nuclear antibody staining, and further performed for Collagen II, Aggrecan, and Collagen I. SOX 9, Aggrecan, Versican, Collagen IA, and Collagen IIA and Collagen IIB human mRNA expression was analyzed by real-time PCR. RESULTS: At magnetic resonance imaging all injured discs demonstrated degenerative signs. Cell/gel discs showed fewer changes compared with cell/med discs and only injured discs at later time points. hMSCs were detected in 9 of 10 of the cell/gel discs and in 8 of 9 of the cell/med discs. Immunostaining for Aggrecan and Collagen type II expression were observed in NP after 3 and 6 months in gel/cell discs and colocalized with the antihuman nuclear antibody. mRNA expression of Collagen IIA, Collagen IIB, Versican, Collagen 1A, Aggrecan, and SOX9 were detected in both cell/med and cell/gel discs at the time points 3 and 6 months by real-time PCR. CONCLUSION: 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.