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

Autologous cell therapy (ACT) is primarily used in diabetic patients with chronic limb-threatening ischemia (CLTI) who are not candidates for standard revascularization. According to current research, this therapy has been shown in some studies to be effective in improving ischemia parameters, decreasing the major amputation rate, and in foot ulcer healing. This review critically evaluates the efficacy of ACT in patients with no-option CLTI, discusses the use of mononuclear and mesenchymal stem cells, and compares the route of delivery of ACT. In addition to ACT, we also describe the use of new revascularization strategies, e.g., nanodiscs, microbeads, and epigenetics, that could enhance the therapeutic effect. The main aim is to summarize new findings on subcellular and molecular levels with the clinical aspects of ACT.

• MeSH
• autologní transplantace * MeSH
• buněčná a tkáňová terapie metody   MeSH
• chronická kritická ischemie končetin terapie   MeSH
• diabetes mellitus terapie   MeSH
• ischemie terapie   MeSH
• lidé MeSH
• transplantace mezenchymálních kmenových buněk metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

We have recently developed a model of pancreatic islet transplantation into a decellularized pancreatic tail in rats. As the pancreatic skeletons completely lack endothelial cells, we investigated the effect of co-transplantation of mesenchymal stem cells and endothelial cells to promote revascularization. Decellularized matrix of the pancreatic tail was prepared by perfusion with Triton X-100, sodium dodecyl sulfate and DNase solution. Isolated pancreatic islets were infused into the skeletons via the splenic vein either alone, together with adipose tissue-derived mesenchymal stem cells (adMSCs), or with a combination of adMSCs and rat endothelial cells (rat ECs). Repopulated skeletons were transplanted into the subcutaneous tissue and explanted 9 days later for histological examination. Possible immunomodulatory effects of rat adMSCs on the survival of highly immunogenic green protein-expressing human ECs were also tested after their transplantation beneath the renal capsule. The immunomodulatory effects of adMSCs were also tested in vitro using the Invitrogen Click-iT EdU system. In the presence of adMSCs, the proliferation of splenocytes as a response to phytohaemagglutinin A was reduced by 47% (the stimulation index decreased from 1.7 to 0.9, P = 0.008) and the reaction to human ECs was reduced by 58% (the stimulation index decreased from 1.6 to 0.7, P = 0.03). Histological examination of the explanted skeletons seeded only with the islets showed their partial disintegration and only a rare presence of CD31-positive cells. However, skeletons seeded with a combination of islets and adMSCs showed preserved islet morphology and rich vascularity. In contrast, the addition of syngeneic rat ECs resulted in islet-cell necrosis with only few endothelial cells present. Live green fluorescence-positive endothelial cells transplanted either alone or with adMSCs were not detected beneath the renal capsule. Though the adMSCs significantly reduced in vitro proliferation stimulated by either phytohaemagglutinin A or by xenogeneic human ECs, in vivo co-transplanted adMSCs did not suppress the post-transplant immune response to xenogeneic ECs. Even in the syngeneic model, ECs co-transplantation did not lead to sufficient vascularization in the transplant area. In contrast, islet co-transplantation together with adMSCs successfully promoted the revascularization of extracellular matrix in the subcutaneous tissue.

• MeSH
• decelularizovaná extracelulární matrix MeSH
• endoteliální buňky MeSH
• fyziologická neovaskularizace * MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• Langerhansovy ostrůvky * imunologie   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * MeSH
• pankreas MeSH
• transplantace Langerhansových ostrůvků * metody   MeSH
• transplantace mezenchymálních kmenových buněk * metody   MeSH
• tuková tkáň * cytologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Human mesenchymal stem cells (hMSCs) are mesoderm-derived adult stem cells with self-proliferation capacity, pluripotent differentiation potency, and excellent histocompatibility. These advantages make hMSCs a promising tool in clinical application. However, the majority of clinical trials using hMSC therapy for diverse human diseases do not achieve expectations, despite the prospective pre-clinical outcomes in animal models. This is partly attributable to the intrinsic heterogeneity of hMSCs. In this review, the cause of heterogeneity in hMSCs is systematically discussed at multiple levels, including isolation methods, cultural conditions, donor-to-donor variation, tissue sources, intra-tissue subpopulations, etc. Additionally, the effect of hMSCs heterogeneity on the contrary role in tumor progression and immunomodulation is also discussed. The attempts to understand the cellular heterogeneity of hMSCs and its consequences are important in supporting and improving therapeutic strategies for hMSCs.

• MeSH
• buněčná diferenciace fyziologie   MeSH
• lidé MeSH
• mezenchymální kmenové buňky * MeSH
• transplantace mezenchymálních kmenových buněk * metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The treatment of cartilage defects in trauma injuries and degenerative diseases represents a challenge for orthopedists. Advanced mesenchymal stromal cell (MSC)-based therapies are currently of interest for the repair of damaged cartilage. However, an approved system for MSC delivery and maintenance in the defect is still missing. This study aimed to evaluate the effect of autologous porcine bone marrow MSCs anchored in a commercially available polyglycolic acid-hyaluronan scaffold (Chondrotissue®) using autologous blood plasma-based hydrogel in the repair of osteochondral defects in a large animal model. The osteochondral defects were induced in twenty-four minipigs with terminated skeletal growth. Eight animals were left untreated, eight were treated with Chondrotissue® and eight received Chondrotissue® loaded with MSCs. The animals were terminated 90 days after surgery. Macroscopically, the untreated defects were filled with newly formed tissue to a greater extent than in the other groups. The histological evaluations showed that the defects treated with Chondrotissue® and Chondrotissue® loaded with pBMSCs contained a higher amount of hyaline cartilage and a lower amount of connective tissue, while untreated defects contained a higher amount of connective tissue and a lower amount of hyaline cartilage. In addition, undifferentiated connective tissue was observed at the edges of defects receiving Chondrotissue® loaded with MSCs, which may indicate the extracellular matrix production by transplanted MSCs. The immunological analysis of the blood samples revealed no immune response activation by MSCs application. This study demonstrated the successful and safe immobilization of MSCs in commercially available scaffolds and defect sites for cartilage defect repair.

• MeSH
• hydrogely MeSH
• kloubní chrupavka * chirurgie   MeSH
• krevní plazma MeSH
• mezenchymální kmenové buňky * fyziologie   MeSH
• miniaturní prasata MeSH
• modely u zvířat MeSH
• prasata MeSH
• tkáňové inženýrství MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• studie ADMIRE-CD, darvadstrocel,
• MeSH
• Crohnova nemoc * komplikace   MeSH
• koordinovaný terapeutický postup MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• rektální píštěl * chirurgie   etiologie   terapie   MeSH
• transplantace mezenchymálních kmenových buněk metody   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Tuková tkáň je komplexní orgán s různými funkcemi. Působí jako zásobárna energie, tepelný izolant a tlumič nárazů a zastává také roli v endokrinním systému. V posledních letech byl objeven její regenerační a protizánětlivý potenciál. Za tyto funkce jsou zodpovědné různé typy progenitorových, kmenových a zralých buněk jiných než adipocyty, které se nacházejí v tukové tkáni a souhrnně se označují jako stromální vaskulární frakce. V retikulární dermis tukové buňky obklopují vlasové folikuly a úzce regulují vlasový cyklus. Intradermální progenitorové adipocyty jsou metabolicky aktivní a vylučují řadu signálních molekul, které jsou zodpovědné za indukci anagenní fáze a růst nových vlasů. V tomto přehledu se zabýváme účinností kmenových buněk odvozených z tukové tkáně při léčbě alopecie v klinických studiích.

Tuková tkáň je komplexní orgán s různými funkcemi. Působí jako zásobárna energie, tepelný izolant a tlumič nárazů a zastává také roli v endokrinním systému. V posledních letech byl objeven její regenerační a protizánětlivý potenciál. Za tyto funkce jsou zodpovědné různé typy progenitorových, kmenových a zralých buněk jiných než adipocyty, které se nacházejí v tukové tkáni a souhrnně se označují jako stromální vaskulární frakce. V retikulární dermis tukové buňky obklopují vlasové folikuly a úzce regulují vlasový cyklus. Intradermální progenitorové adipocyty jsou metabolicky aktivní a vylučují řadu signálních molekul, které jsou zodpovědné za indukci anagenní fáze a růst nových vlasů. V tomto přehledu se zabýváme účinností kmenových buněk odvozených z tukové tkáně při léčbě alopecie v klinických studiích.

• MeSH
• alopecie * terapie   MeSH
• buňky stromatu * MeSH
• lidé MeSH
• mezenchymální kmenové buňky cytologie   metabolismus   MeSH
• transplantace mezenchymálních kmenových buněk MeSH
• tuková tkáň cytologie   metabolismus   MeSH
• Check Tag
• lidé MeSH

Úvod: Idiopatické střevní záněty jsou onemocnění, jejichž incidence celosvětově stoupá. Navzdory pokroku v konzervativní i chirurgické léčbě významná část pacientů nedosáhne kompletní remise a musí podstoupit opakované operace. Léčba kmenovými buňkami (MSC) představuje novou alternativu imunomodulační léčby. Metody: Provedli jsme systematický přehled literatury zabývající se použitím mezenchymálních kmenových buněk k léčbě IBD. K jejich vyhledávání byla použita databáze PubMed, zařazeny byly původní studie publikované mezi lety 2015 a 2021. Výsledky: Nalezeno bylo celkem 80 citací, z nich po výběru bylo do přehledu zahrnuto 21 klinických studií a 47 experimentálních studií. Závěr: Účinnost MSC v léčbě perianální Crohnovy choroby je přinejmenším srovnatelná se současnými léčebnými metodami. Pozitivní efekt byl rovněž prokázán na zvířecích modelech luminální choroby nebo enterokutánní píštěle. Výsledky po systémovém podání u IBD pacientů jsou zatím nejednoznačné.

Introduction: The incidence of inflammatory bowel disease is increasing worldwide and, despite advances in conservative and surgical treatment, a significant proportion of patients do not achieve complete remission and have to undergo repeated surgical procedures. Stem cell therapy is a new alternative to immunomodulatory therapy. Methods: We performed a systematic review of the literature dealing with the use of mesenchymal stem cells for the treatment of IBD. The PubMed database was searched and original studies published between 2015 and 2021 were included. Results: A total of 80 citations were found, of which 21 clinical studies and 47 experimental studies were included in the review. Conclusion: The efficacy of MSCs in the treatment of perianal Crohn‘s disease is at least comparable to current therapies. A positive effect of MSC administration has also been demonstrated in animal models of luminal disease or enterocutaneous fistula. The results after systemic administration in IBD patients are still ambiguous. Key words: inflammatory bowel disease,

• MeSH
• Crohnova nemoc terapie   MeSH
• idiopatické střevní záněty * terapie   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• rektovaginální píštěl terapie   MeSH
• střevní píštěle terapie   MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• Check Tag
• lidé MeSH

An encounter of the developing immune system with an antigen results in the induction of immunological areactivity to this antigen. In the case of transplantation antigens, the application of allogeneic hematopoietic cells induces a state of neonatal transplantation tolerance. This tolerance depends on the establishment of cellular chimerism, when allogeneic cells survive in the neonatally treated recipient. Since mesenchymal stem/stromal cells (MSCs) have been shown to have low immunogenicity and often survive in allogeneic recipients, we attempted to use these cells for induction of transplantation tolerance. Newborn (less than 24 h old) C57BL/6 mice were injected intraperitoneally with 5 × 106 adipose tissue-derived MSCs isolated from allogeneic donors and the fate and survival of these cells were monitored. The impact of MSC application on the proportion of cell populations of the immune system and immunological reactivity was assessed. In addition, the survival of skin allografts in neonatally treated recipients was tested. We found that in vitro expanded MSCs did not survive in neonatal recipients, and the living MSCs were not detected few days after their application. Furthermore, there were no significant changes in the proportion of individual immune cell populations including CD4+ cell lineages, but we detected an apparent shift to the production of Th1 cytokines IL-2 and IFN-γ in neonatally treated mice. However, skin allografts in the MSC-treated recipients were promptly rejected. These results therefore show that in vitro expanded MSCs do not survive in neonatal recipients, but induce a cytokine imbalance without induction of transplantation tolerance.

• MeSH
• cytokiny MeSH
• interleukin-2 MeSH
• mezenchymální kmenové buňky * MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• novorozená zvířata MeSH
• transplantace mezenchymálních kmenových buněk * MeSH
• transplantační tolerance MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Injection of autologous adipose tissue (AT) has recently been demonstrated to be an effective and safe treatment for anal fistulas. AT mesenchymal stem cells (AT-MSCs) mediate the healing process, but the relationship between molecular characteristics of AT-MSCs of the injected AT and fistula healing has not been adequately studied. Thus we aimed to characterize the molecular and functional properties of AT-MSCs isolated from autologous AT injected as a treatment of cryptogenic high transsphincteric perianal fistulas and correlate these findings to the healing process. METHODS: 27 patients (age 45 ± 2 years) diagnosed with perianal fistula were enrolled in the study and treated with autologous AT injected around the anal fistula tract. AT-MSCs were isolated for cellular and molecular analyses. The fistula healing was evaluated by MRI scanning after 6 months of treatment. AT-MSC phenotype was compared between responders and non-responders with respect to fistula healing. RESULTS: 52% of all patients exhibited clinical healing of the fistulas as evaluated 6 months after last injection. Cultured AT-MSCs in the responder group had a lower short-term proliferation rate and higher osteoblast differentiation potential compared to non-responder AT-MSCs. On the other hand, adipocyte differentiation potential of AT-MSCs was higher in non-responder group. Interestingly, AT-MSCs of responders exhibited lower expression of inflammatory and senescence associated genes such as IL1B, NFKB, CDKN2A, TPB3,TGFB1. CONCLUSION: Our data suggest that cellular quality of the injected AT-MSCs including cell proliferation, differentiation capacity and secretion of proinflammatory molecules may provide a possible mechanism underlying fistula healing. Furthermore, these biomarkers may be useful to predict a positive fistula healing outcome. TRIAL REGISTRATION: NTC04834609, Registered 6 April 2021. https://clinicaltrials.gov/ct2/show/NCT04834609.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezenchymální kmenové buňky * MeSH
• rektální píštěl * genetika   terapie   MeSH
• transplantace mezenchymálních kmenových buněk * metody   MeSH
• tuková tkáň MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinická studie MeSH
• práce podpořená grantem MeSH