BACKGROUND: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking. AIMS: To examine the usability of darvadstrocel therapy in managing perianal CD. METHODS: We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression. RESULTS: Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported. CONCLUSION: Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.
- MeSH
- Crohnova nemoc * terapie komplikace MeSH
- dospělí MeSH
- indukce remise MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- rektální píštěl * terapie etiologie MeSH
- retrospektivní studie MeSH
- spokojenost pacientů MeSH
- transplantace mezenchymálních kmenových buněk * metody škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
BACKGROUND: Portal vein embolization (PVE) and PVE with autologous mesenchymal stem cell application (PVE-MSC) increases future liver remnant volume (FLRV). The aim of this study was to compare both methods from the aspect of FLRV growth, progression of colorectal liver metastases (CLM), CLM resectability and long-term results. PATIENTS AND METHODS: Fifty-five patients with CLM and insufficient FLRV were included in the study. FLVR growth and CLM volume were evaluated using computed tomography. Liver resection was performed in patients with FLVR >30% of total liver volume. RESULTS: In the PVE (N=27) group, FLRV growth was observed in 23 patients (85.2%) and in 100% of patients in the PVE-MSC (N=28) group (p<0.05). The rapidity of FLRV and CLM growth did not differ between groups. R0 resection was performed in 14 (51.8%) and 24 (85.7%) patients from the PVE and PVE-MSC (p<0.02) groups, respectively. The 3-year overall and progression-free survival rates were 85.75% and 9.3% in the PVE group and 68.7% and 17.1% in the PVE-MSC group, respectively (p<0.67 and p<0.84, respectively). CONCLUSION: PVE-MSC allows for more effective growth of FLRV and resectability of CLM compared to PVE. The two methods do not differ in their long-term results.
- MeSH
- časové faktory MeSH
- Kaplanův-Meierův odhad MeSH
- kolorektální nádory mortalita patologie MeSH
- kombinovaná terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory jater mortalita sekundární terapie MeSH
- přežití po terapii bez příznaků nemoci MeSH
- regenerace jater * MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- senioři MeSH
- terapeutická embolizace škodlivé účinky metody MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky mortalita MeSH
- transplantace mezenchymálních kmenových buněk * škodlivé účinky mortalita MeSH
- vena portae * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Stem cells biology is one of the most frequent topic of physiological research of today. Spinal fusion represents common bone biology challenge. It is the indicator of osteoinduction and new bone formation on ectopic model. The purpose of this study was to establish a simple model of spinal fusion based on a rat model including verification of the possible use of titanium microplates with hydroxyapatite scaffold combined with human bone marrow-derived mesenchymal stem cells (MSCs). Spinous processes of two adjacent vertebrae were fixed in 15 Wistar rats. The space between bony vertebral arches and spinous processes was either filled with augmentation material only and covered with a resorbable collagen membrane (Group 1), or filled with augmentation material loaded with 5 × 10⁶ MSCs and covered with a resorbable collagen membrane (Group 2). The rats were sacrificed 8 weeks after the surgery. Histology, histomorphometry and micro-CT were performed. The new model of interspinous fusion was safe, easy, inexpensive, with zero mortality. We did not detect any substantial pathological changes or tumor formation after graft implantation. We observed a nonsignificant effect on the formation of new bone tissue between Group 1 and Group 2. In the group with MSCs (Group 2) we described minor inflamatory response which indicates the imunomodulational and antiinflamatory role of MSCs. In conclusion, this new model proved to be easy to use in small animals like rats.
- MeSH
- bederní obratle patofyziologie radiografie chirurgie MeSH
- časové faktory MeSH
- fúze páteře škodlivé účinky přístrojové vybavení metody MeSH
- hydroxyapatit MeSH
- kostní destičky MeSH
- kultivované buňky MeSH
- lidé MeSH
- modely u zvířat MeSH
- osteogeneze MeSH
- osteointegrace MeSH
- potkani Wistar MeSH
- protézy - design MeSH
- regenerace * MeSH
- rentgenová mikrotomografie MeSH
- titan MeSH
- tkáňové podpůrné struktury MeSH
- transplantace mezenchymálních kmenových buněk škodlivé účinky přístrojové vybavení metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
BACKGROUND: Mesenchymal stromal cells attract much interest in tissue regeneration because of their capacity to differentiate into mesodermal origin cells, their paracrine properties and their possible use in autologous transplantations. The aim of this study was to investigate the safety and reparative potential of implanted human mesenchymal stromal cells (hMSCs), prepared under Good Manufacturing Practice (GMP) conditions utilizing human mixed platelet lysate as a culture supplement, in a collagenase Achilles tendon injury model in rats. METHODS: Eighty-one rats with collagenase-induced injury were divided into two groups. The first group received human mesenchymal stromal cells injected into the site of injury 3 days after lesion induction, while the second group received saline. Biomechanical testing, morphometry and semiquantitative immunohistochemistry of collagens I, II and III, versican and aggrecan, neovascularization, and hMSC survival were performed 2, 4, and 6 weeks after injury. RESULTS: Human mesenchymal stromal cell-treated rats had a significantly better extracellular matrix structure and a larger amount of collagen I and collagen III. Neovascularization was also increased in hMSC-treated rats 2 and 4 weeks after tendon injury. MTCO2 (Cytochrome c oxidase subunit II) positivity confirmed the presence of hMSCs 2, 4 and 6 weeks after transplantation. Collagen II deposits and alizarin red staining for bone were found in 6 hMSC- and 2 saline-treated tendons 6 weeks after injury. The intensity of anti-versican and anti-aggrecan staining did not differ between the groups. CONCLUSIONS: hMSCs can support tendon healing through better vascularization as well as through larger deposits and better organization of the extracellular matrix. The treatment procedure was found to be safe; however, cartilage and bone formation at the implantation site should be taken into account when planning subsequent in vivo and clinical trials on tendinopathy as an expected adverse event.
- MeSH
- Achillova šlacha účinky léků zranění MeSH
- biomechanika MeSH
- buněčná diferenciace MeSH
- extracelulární matrix metabolismus MeSH
- fyziologická neovaskularizace MeSH
- hojení ran * MeSH
- karcinogeneze MeSH
- kolagenasy škodlivé účinky MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mezenchymální kmenové buňky cytologie MeSH
- osteogeneze MeSH
- pluripotentní kmenové buňky transplantace MeSH
- poranění šlachy chemicky indukované patologie patofyziologie chirurgie MeSH
- transplantace mezenchymálních kmenových buněk * škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This study appears from an experiment previously carried out in New Zealand white rabbits. Allogenic mesenchymal stem cells (MSCs) were transplanted into an iatrogenically-created defect in the lateral section of the distal physis of the left femur in 10 miniature pigs. The right femur with the same defect served as a control. To transfer MSCs, a freshly prepared porous scaffold was used, based on collagen and chitosan, constituting a compact tube into which MSCs were implanted. The pigs were euthanized four months after the transplantation. On average, the left femur with transplanted MSCs grew more in length (0.56±0.14 cm) compared with right femurs with physeal defect without transplanted MSCs (0.14±0.3 cm). The average angular (valgus) deformity of the left femur had an angle point of 0.78°, following measurement and X-ray examination, whereas in the right femur without transplantation it was 3.7°. The initial results indicate that preventive transplantation of MSCs into a physeal defect may prevent valgus deformity formation and probably also reduce disorders of the longitudinal bone growth. This part of our experiment is significant in the effort to advance MSCs application in human medicine by using pig as a model, which is the next step after experimenting on rabbits.
- MeSH
- autologní transplantace MeSH
- časové faktory MeSH
- femur chirurgie radiografie růst a vývoj MeSH
- financování organizované MeSH
- fixace fraktur metody škodlivé účinky MeSH
- fraktury femuru chirurgie patofyziologie radiografie MeSH
- kultivované buňky MeSH
- miniaturní prasata MeSH
- modely nemocí na zvířatech MeSH
- nestejná délka dolních končetin MeSH
- osteogeneze MeSH
- prasata MeSH
- tkáňové podpůrné struktury MeSH
- transplantace mezenchymálních kmenových buněk škodlivé účinky MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH