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1.
BJU Int ; 131(5): 530-539, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36522728

RESUMO

OBJECTIVES: To investigate the prevalence of prostate cancer in men attending evaluation for haematuria, as this could help healthcare providers to determine whether men with haematuria should have prostate examinations performed. METHODS: The study was performed according to a pre-specified protocol uploaded to the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022299383). A systematic search of MEDLINE, Ovid and Google Scholar was performed in December 2021. Two independent researchers evaluated all titles, available abstracts, and full texts. We included studies on adult men (aged ≥18 years) describing haematuria and prostate cancer. RESULTS: We screened 4252 titles and abstracts when available and assessed 350 studies in full text. In total, 65 studies were included and 42 was summarised in a meta-analysis. In total, 18 752 men with haematuria were included, and the pooled prevalence (95% confidence interval [CI]) of prostate cancer was 3.0% (2.0-4.1%). In men with macroscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 5.9% (2.9-9.9%; n = 265/5373). In men with microscopic haematuria, the pooled prevalence (95% CI) of prostate cancer was 1.4% (0.8-2.2%; n = 71/6642). CONCLUSION: Our findings indicate that the prevalence of prostate cancer is considerable in men attending evaluation for haematuria. Therefore, digital rectal examination and prostate-specific antigen measurement should become a standard procedure for all men with haematuria, especially for men with macroscopic haematuria.


Assuntos
Hematúria , Neoplasias da Próstata , Masculino , Adulto , Humanos , Adolescente , Hematúria/epidemiologia , Hematúria/etiologia , Hematúria/diagnóstico , Prevalência , Neoplasias da Próstata/complicações , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/diagnóstico , Exame Retal Digital
2.
Int J Mol Sci ; 23(3)2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35163613

RESUMO

Erectile dysfunction is a common complication associated with type 2 diabetes mellitus (T2DM) and after prostatectomy in relation to cancer. The regenerative effect of cultured adipose-derived stem cells (ASCs) for ED therapy has been documented in multiple preclinical trials as well as in recent Pase 1 trials in humans. However, some studies indicate that diabetes negatively affects the mesenchymal stem cell pool, implying that ASCs from T2DM patients could have impaired regenerative capacity. Here, we directly compared ASCs from age-matched diabetic Goto-Kakizaki (ASCGK) and non-diabetic wild type rats (ASCWT) with regard to their phenotypes, proteomes and ability to rescue ED in normal rats. Despite ASCGK exhibiting a slightly lower proliferation rate, ASCGK and ASCWT proteomes were more or less identical, and after injections to corpus cavernosum they were equally efficient in restoring erectile function in a rat ED model entailing bilateral nerve crush injury. Moreover, molecular analysis of the corpus cavernosum tissue revealed that both ASCGK and ASCWT treated rats had increased induction of genes involved in recovering endothelial function. Thus, our finding argues that T2DM does not appear to be a limiting factor for autologous adipose stem cell therapy when correcting for ED.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Disfunção Erétil/terapia , Transplante de Células-Tronco , Tecido Adiposo/citologia , Animais , Células Cultivadas , Disfunção Erétil/etiologia , Masculino , Ratos , Células-Tronco
3.
Ann Plast Surg ; 80(2): 181-187, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28737557

RESUMO

INTRODUCTION: There is a rising interest in adipose-derived stromal cells for clinical use; however, it is unknown whether freshly isolated stromal cells (SVF) or culture-expanded cells (ASCs) are more efficacious. We therefore aimed to compare the 2 cellular therapies in an in vivo model of angiogenesis, the ischemic flap in rats, which induces acute ischemia. We also aimed to determine the importance of cell presence and the host immune response. METHODS: A total of 96 rats (n = 12 in each group) were used, and in each rat, a caudally based random flap measuring 2 × 7 cm was made. The study was conducted in 3 phases. First, each rat was treated with human SVF cells, human ASCs, or vehicle. Second, each rat was treated with human SVF, human SVF lysate, or vehicle. Finally, each rat was treated with rat (autologous) SVF cells or vehicle. Flap survival, vessel density, and stromal cell retention were evaluated after 7 days. RESULTS: The mean survival rates for SVF treatment regardless of human or autologous origin were significantly increased as compared with the control group. Adipose stem/stromal cell and SVF lysate injection did not increase flap survival. Vessel density was increased for human and rat SVF and human ASC but not for SVF lysate. Human cells were not detected in the flaps after 7 days. CONCLUSIONS: Flap survival increased with SVF treatment regardless of human or autologous origin, suggesting that increased flap survival is independent of the host immune response. All cell injections lead to increased vessel density, but it did not necessarily lead to increased flap survival. Further research should elaborate which molecular events make SVF treatment more efficacious than ASC.


Assuntos
Isquemia/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Complicações Pós-Operatórias/terapia , Gordura Subcutânea/citologia , Retalhos Cirúrgicos/irrigação sanguínea , Animais , Células Cultivadas , Humanos , Isquemia/etiologia , Masculino , Ratos , Ratos Sprague-Dawley , Transplante Autólogo , Resultado do Tratamento
4.
J Mol Cell Cardiol ; 90: 47-52, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26655949

RESUMO

Heart damage in mammals is generally considered to result in scar formation, whereas zebrafish completely regenerate their hearts following an intermediate and reversible state of fibrosis after apex resection (AR). Recently, using the AR procedure, one-day-old mice were suggested to have full capacity for cardiac regeneration as well. In contrast, using the same mouse model others have shown that the regeneration process is incomplete and that scarring still remains 21 days after AR. The present study tested the hypothesis that like in zebrafish, fibrosis in neonatal mammals could be an intermediate response before the onset of complete heart regeneration. Myocardial damage was performed by AR in postnatal day 1 C57BL/6 mice, and myocardial function and scarring assessed at day 180 using F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) and histology, respectively. AR mice exhibited decreased ejection fraction and wall motion with increased end-diastolic and systolic volumes compared to sham-operated mice. Scarring with collagen accumulation was still substantial, with increased heart size, while cardiomyocyte size was unaffected. In conclusion, these data thus show that apex resection in mice results in irreversible fibrosis and dilated cardiomyopathy suggesting that cardiac regeneration is limited in neonatal mammals and thus distinct from the regenerative capacity seen in zebrafish.


Assuntos
Cardiomiopatia Dilatada/patologia , Cicatriz/patologia , Traumatismos Cardíacos/patologia , Animais , Animais Recém-Nascidos , Pressão Sanguínea , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/etiologia , Proliferação de Células , Tamanho Celular , Cicatriz/diagnóstico por imagem , Cicatriz/etiologia , Fibrose , Fluordesoxiglucose F18 , Traumatismos Cardíacos/complicações , Traumatismos Cardíacos/diagnóstico por imagem , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/patologia , Miócitos Cardíacos/patologia , Tomografia por Emissão de Pósitrons , Regeneração/fisiologia , Especificidade da Espécie , Volume Sistólico , Peixe-Zebra
5.
Development ; 140(18): 3743-53, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23946446

RESUMO

Muscle development and regeneration is tightly orchestrated by a specific set of myogenic transcription factors. However, factors that regulate these essential myogenic inducers remain poorly described. Here, we show that delta-like 1 homolog (Dlk1), an imprinted gene best known for its ability to inhibit adipogenesis, is a crucial regulator of the myogenic program in skeletal muscle. Dlk1(-/-) mice were developmentally retarded in their muscle mass and function owing to inhibition of the myogenic program during embryogenesis. Surprisingly however, Dlk1 depletion improves in vitro and in vivo adult skeletal muscle regeneration by substantial enhancement of the myogenic program and muscle function, possibly by means of an increased number of available myogenic precursor cells. By contrast, Dlk1 fails to alter the adipogenic commitment of muscle-derived progenitors in vitro, as well as intramuscular fat deposition during in vivo regeneration. Collectively, our results suggest a novel and surprising dual biological function of DLK1 as an enhancer of muscle development, but as an inhibitor of adult muscle regeneration.


Assuntos
Envelhecimento/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Desenvolvimento Muscular , Músculo Esquelético/metabolismo , Regeneração/fisiologia , Adipogenia , Adiponectina/metabolismo , Animais , Proteínas de Ligação ao Cálcio , Tamanho Celular , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Tamanho do Órgão , Fenótipo
6.
Ann Plast Surg ; 75(1): 117-23, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24691309

RESUMO

Emerging evidence has shown that adipose tissue is the richest and most accessible source of mesenchymal stem cells. Many different therapies for chronic wounds exist with varying success rates. The capacity of adipose-derived stem cells (ASCs) to promote angiogenesis, secrete growth factors, regulate the inflammatory process, and differentiate into multiple cell types makes them a potential ideal therapy for chronic wounds. The aim of this article was to review all preclinical trials using ASCs in problem wound models. A systematic search was performed and 12 studies were found where different chronic wound models across different animals were treated with ASCs. Different ASC sources and delivery methods were used in the described studies. Studies demonstrated improved wound healing with utilization of ASC, and this treatment modality has so far shown great potential. However, more preclinical studies and large-scale clinical trials are needed to show if the emerging therapy can satisfy expectations.


Assuntos
Adipócitos/transplante , Transplante de Células-Tronco , Cicatrização , Humanos
7.
Plast Reconstr Surg ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38954656

RESUMO

BACKGROUND: Breast cancer-related lymphedema (BCRL) is a debilitating sequela affecting up to one in three breast cancer survivors. Current treatments are palliative and does not address the underlying lymphatic injury. Recently, preclinical and non-randomized studies have shown promising results using Adipose-Derived Regenerative Cells (ADRCs) and lipotransfer in alleviating BCRL through regeneration of lymphatic tissue. However no randomized controlled trial has been performed in an attempt to eliminate a placebo effect. METHODS: This randomized, double-blinded, placebo-controlled trial included patients with no-option, persistent disabling unilateral BCRL. Patients were randomly assigned in a 1:1 ratio to receive either autologous ADRCs (4.20x10 7±1.75x10 7 cells) and 30cc lipotransfer or placebo (saline) to the axilla. The primary outcome was a change in BCRL volume one year after treatment. Secondary outcomes included changes in the quality of life, indocyanine green lymphangiography stage, bioimpedance, and safety. RESULTS: Eighty patients were included, of which 39 were allocated to ADRCs and lipotransfer treatment and 41 to placebo treatment. Baseline characteristics were similar in both groups. One year after treatment, no objective improvements were observed in the treatment or placebo groups. In contrast, significant subjective improvements were noted for both the treatment and placebo groups. CONCLUSION: This trial failed to confirm a benefit of ADRCs and lipotransfer in the treatment of BCRL. These non-confirmatory results suggest that ADRC and lipotransfer should not be recommended for alleviating BCRL at this time. However, we cannot exclude that repeated treatments or higher doses of ADRCs or lipotransfer could yield a clinical effect.

8.
Growth Factors ; 31(3): 81-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23734837

RESUMO

Cardiac fibrosis is a maladaptive response of the injured myocardium and is mediated through a complex interplay between molecular triggers and cellular responses. Interleukin (IL)-1ß is a key inflammatory inducer in cardiac disease and promotes cell invasion and cardiomyocyte injury, but little is known of its impact on fibrosis. A major cornerstone of fibrosis is the differentiation of cardiac fibroblasts (CFs) into myofibroblasts (myoFbs), which is highly promoted by Transforming Growth Factor (TGF)-ß. Therefore, we asked how IL-1ß functionally modulated CF-to-myoFb differentiation. Using a differentiation model of ventricular fibroblasts, we found that IL-1ß instigated substantial anti-fibrogenic effects. In specific, IL-1ß reduced proliferation, matrix activity, cell motility and α-smooth muscle actin expression, which are all hallmarks of myoFb differentiation. These findings suggest that IL-1ß, besides from its acknowledged adverse role in the inflammatory response, can also exert beneficial effects in cardiac fibrosis by actively suppressing differentiation of CFs into fibrogenic myoFbs.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Interleucina-1beta/farmacologia , Miócitos Cardíacos/citologia , Miofibroblastos/citologia , Fator de Crescimento Transformador beta/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Movimento Celular , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Matriz Extracelular/efeitos dos fármacos , Ventrículos do Coração/citologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miofibroblastos/metabolismo , Ratos , Ratos Sprague-Dawley
9.
Sci Rep ; 13(1): 14401, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37658225

RESUMO

Cellular heterogeneity represents a major challenge for regenerative treatment using freshly isolated Adipose Derived Regenerative Cells (ADRCs). Emerging data suggest superior efficacy of ADRCs as compared to the ex vivo expanded and more homogeneous ADRCs (= ASCs) for indications involving (micro)vascular deficiency, however, it remains unknown which ADRC cell subtypes account for the improvement. Surprisingly, we found regarding erectile dysfunction (ED) that the number of injected CD31+ ADRCs correlated positively with erectile function 12 months after one bolus of autologous ADRCs. Comprehensive in vitro and ex vivo analyses confirmed superior pro-angiogenic and paracrine effects of human CD31+ enriched ADRCs compared to the corresponding CD31- and parent ADRCs. When CD31+, CD31- and ADRCs were co-cultured in aortic ring- and corpus cavernous tube formation assays, the CD31+ ADRCs induced significantly higher tube development. This effect was corroborated using conditioned medium (CM), while quantitative mass spectrometric analysis suggested that this is likely explained by secretory pro-angiogenic proteins including DKK3, ANGPT2, ANAX2 and VIM, all enriched in CD31+ ADRC CM. Single-cell RNA sequencing showed that transcripts of the upregulated and secreted proteins were present in 9 endothelial ADRC subsets including endothelial progenitor cells in the heterogenous non-cultured ADRCs. Our data suggest that the vascular benefit of using ADRCs in regenerative medicine is dictated by CD31+ ADRCs.


Assuntos
Máculas Acústicas , Líquidos Corporais , Humanos , Masculino , Proteínas Angiogênicas , Bioensaio , Transporte Biológico , Meios de Cultivo Condicionados
10.
Stem Cells Transl Med ; 10(6): 844-854, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33594819

RESUMO

Patients with breast cancer-related lymphedema (BCRL) have reduced quality of life and arm function. Current treatments are palliative, and treatments improving lymphedema are lacking. Preclinical studies have suggested that adipose-derived regenerative cells (ADRCs) can alleviate lymphedema. We, therefore, aimed to assess whether ADRCs can alleviate lymphedema in clinical reality with long-term follow-up. We treated 10 patients with BCRL using ADRCs and a scar-releasing lipotransfer to the axillary region, and all patients were followed 1, 3, 6, 12, and 48 months after treatment. The primary endpoint was change in arm volume. Secondary endpoints were safety, change in lymphedema symptoms, quality of life, lymphedema-associated cellulitis, and conservative treatment use. There was no significant decrease in BCRL volume after treatment. However, self-reported upper extremity disability and arm heaviness and tension improved. Six patients reduced their use of conservative BCRL treatment. Five patients felt that their BCRL had improved substantially, and four of these would redo the treatment. We did not observe any cases of locoregional breast cancer recurrence. In this phase I study with 4 years of follow-up, axillary delivered ADRCs and lipotransfer were safe and feasible and improved BCRL symptoms and upper extremity function. Randomized controlled trials are needed to confirm the results of this study.


Assuntos
Tecido Adiposo , Linfedema Relacionado a Câncer de Mama , Neoplasias da Mama , Transplante de Células-Tronco , Tecido Adiposo/citologia , Tecido Adiposo/transplante , Linfedema Relacionado a Câncer de Mama/terapia , Neoplasias da Mama/complicações , Neoplasias da Mama/terapia , Feminino , Seguimentos , Humanos , Recidiva Local de Neoplasia , Qualidade de Vida
11.
Regen Med ; 16(2): 117-130, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33764157

RESUMO

Background: Polycaprolactone (PCL) scaffolds exhibit high biocompatibility and are attractive as vascular conduits. Materials & methods: PCL tubes were cultivated in bioreactor with human adipose regenerative cells to assess ex vivo cytocompatibility, whereas in vivo PCL tube patency was evaluated in sheep carotid bypass with and without antithrombotic treatment. Results:Ex vivo results revealed increasing adipose regenerative cells on PCL using dynamic bioreactor culturing. In vivo data showed that 67% (2/3) of grafts in the antithrombotic group were patent at day 28, while 100% (3/3) of control grafts were occluded already during the first week due to thrombosis. Histology showed that patent PCL grafts were recellularized by host cells. Conclusion: PCL tubes may work as small diameter vascular scaffolds under antithrombotic treatment.


Assuntos
Fibrinolíticos , Enxerto Vascular , Animais , Prótese Vascular , Fibrinolíticos/farmacologia , Poliésteres , Ovinos
13.
Sleep ; 33(2): 169-76, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20175400

RESUMO

STUDY OBJECTIVES: The International Classification of Sleep Disorders (ICSD-2) criteria for low CSF hypocretin-1 levels (CSF hcrt-1) still need validation as a diagnostic tool for narcolepsy in different populations because inter-assay variability and different definitions of hypocretin deficiency complicate direct comparisons of study results. DESIGN AND PARTICIPANTS: Interviews, polysomnography, multiple sleep latency test, HLA-typing, and CSF hcrt-1 measurements in Danish patients with narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (NwC), CSF hcrt-1 measurements in other hypersomnias, neurological and normal controls. Comparisons of hypocretin deficiency and frequency of HLA-DQB1*0602-positivity in the Danish and eligible NC and NwC populations (included via MEDLINE search), by (re)calculation of study results using the ICSD-2 criterion for low CSF hcrt-1 (< 30% of normal mean). MEASUREMENTS AND RESULTS: In Danes, low CSF hcrt-1 was present in 40/46 NC, 3/14 NwC and 0/106 controls (P < 0.0001). Thirty-nine of 41 NC and 4/13 NwC patients were HLA-DQB1*0602-positive (P < 0.01). Hypocretin-deficient NC patients had higher frequency of cataplexy, shorter mean sleep latency, more sleep onset REM periods (P < 0.05) and more awakenings (NS) than did NC patients with normal CSF hcrt-1. Across populations, low CSF hcrt-1 and HLA-DQB1*0602-positivity characterized the majority of NC (80% to 100%, P = 0.53; 80% to 100%, P = 0.11) but a minority of NwC patients (11% to 29%, P = 0.75; 29% to 89%, P = 0.043). CONCLUSION: The study provides evidence that hypocretin deficiency causes a more severe NC phenotype. The ICSD-2 criterion for low CSF hcrt-1 (< 30% of normal mean) is valid for diagnosing NC, but not NwC. HLA-typing should precede CSF hcrt-1 measurements because hypocretin deficiency is rare in HLA-DQB1*0602-negative patients.


Assuntos
Cataplexia/diagnóstico , Peptídeos e Proteínas de Sinalização Intracelular/líquido cefalorraquidiano , Narcolepsia/diagnóstico , Neuropeptídeos/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Cataplexia/líquido cefalorraquidiano , Cataplexia/genética , Criança , Dinamarca , Distúrbios do Sono por Sonolência Excessiva/líquido cefalorraquidiano , Distúrbios do Sono por Sonolência Excessiva/diagnóstico , Feminino , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Humanos , Hipóxia Encefálica/líquido cefalorraquidiano , Hipóxia Encefálica/diagnóstico , Hipóxia Encefálica/genética , Classificação Internacional de Doenças , Síndrome de Kleine-Levin/líquido cefalorraquidiano , Síndrome de Kleine-Levin/diagnóstico , Síndrome de Kleine-Levin/genética , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Narcolepsia/líquido cefalorraquidiano , Narcolepsia/genética , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/genética , Orexinas , Fenótipo , Polissonografia , Valores de Referência , Adulto Jovem
14.
Stem Cells ; 27(7): 1571-81, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19544463

RESUMO

Recent remarkable studies have reported that clonogenic putative cardiac stem cells (CSCs) with cardiomyogenic potential migrate from heart tissue biopsies during ex vivo culture, and that these CSCs self-organize into spontaneously beating cardiospheres (CSs). Such data have provided clear promise that injured heart tissue may be repaired by stem cell therapy using autologous CS-derived cells. By further examining CSs from the original CS protocol using immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and microscopic analysis, we here report a more mundane result: that spontaneously beating CSs from neonatal rats likely consist of contaminating myocardial tissue fragments. Thus, filtering away these tissue fragments resulted in CSs without cardiomyogenic potential. Similar data were obtained with CSs derived from neonatal mice as wells as adult rats/mice. Additionally, using in vitro culture, fluorescence-activated cell sorting, and immunofluorescence, we demonstrate that these CSs are generated by cellular aggregation of GATA-4(+)/collagen I(+)/alpha-smooth muscle actin (SMA)(+)/CD45(-) cells rather than by clonal cell growth. In contrast, we found that the previously proposed CS-forming cells, dubbed phase bright cells, were GATA-4(-)/collagen I(-)/alpha-SMA(-)/CD45(+) and unable to form CSs by themselves. Phenotypically, the CS cells largely resembled fibroblasts, and they lacked cardiomyogenic as well as endothelial differentiation potential. Our data imply that the murine CS model is unsuitable as a source of CSCs with cardiomyogenic potential, a result that is in contrast to previously published data. We therefore suggest, that human CSs should be further characterized with respect to phenotype and differentiation potential before initiating human trials.


Assuntos
Miócitos Cardíacos/citologia , Miócitos Cardíacos/fisiologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Animais , Animais Recém-Nascidos , Técnicas de Cultura de Células , Diferenciação Celular , Células Cultivadas , Citometria de Fluxo , Imunofluorescência , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Mater Sci Eng C Mater Biol Appl ; 116: 111214, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32806303

RESUMO

Diabetic erectile dysfunction has witnessed extensive preclinical and clinical explorations of intracavernous injection of stem cells therapy. However, intracavernous injection of stem cells for diabetic erectile dysfunction is challenged by rapid diffusion from cavernous sinus. Here, we found that a benzaldehyde terminated poly (ethylene glycol)/glycol chitosan (CHO-PEG/GCS) hydrogel with injectability and self-healability served as a stem cell carrier to prolong cell retention in corpus cavernosum. It was able to gelate under physiological condition and encapsulate adipose stem cells (ASCs) without reducing proliferation after injection. Encapsulated labelled ASCs presented higher fluorescence than non-encapsulated ones in the region of penis at 14 days after intracavernous injection in male rats. CHO-PEG/GCS hydrogel enhanced ASCs to ameliorate diabetes-induced fibrosis and apoptosis of CD31-positive endothelial cells, α-SMA-positive smooth muscle and NeuN-positive neural fibers 12 weeks post-operation. It also synergized with ASCs to elevate cGMP level and promote erectile function. CHO-PEG/GCS hydrogel serves as a promising stem cell carrier in conditions requiring injection and in situ gelation to prolong cell retention.


Assuntos
Diabetes Mellitus , Disfunção Erétil , Animais , Células Endoteliais , Disfunção Erétil/tratamento farmacológico , Humanos , Hidrogéis , Masculino , Ratos , Ratos Sprague-Dawley , Células-Tronco
16.
Urology ; 121: 203.e6-203.e13, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29958973

RESUMO

OBJECTIVE: To explore safety in adipose-derived regenerative cells (ADRC) therapy, treating erectile dysfunction (ED). METHODS: Twenty-one patients with ED after radical prostatectomy, with no signs of recovery using conventional therapy, received a single intracavernous injection of autologous ADRC and were followed for 1 year. Six men were incontinent, and 15 were continent at inclusion. The primary (safety of ADRC therapy) and secondary endpoints (sexual function) were evaluated at 1, 3, 6, and 12 months after ADRC injection by registration of adverse events and validated questionnaires using the international index of erectile function-5 and erection hardness score. RESULTS: No serious adverse events occurred, but 8 reversible minor events related to the liposuction were noted. Eight out of 15 (53%) patients in the continent group reported erectile function sufficient for intercourse at 12 months. Baseline median international index of erectile function-5 scores (6.0; interquartile range [IQR] 3) were unchanged 1 month after the treatment, but significantly increased after 6 to 7 (IQR 17). This effect was sustained at 12 months (median 8; IQR 14). We did not see any improvements in erectile function in the group of incontinent men or among men with ED prior to radical prostatectomy. CONCLUSION: Intracavernous injection of ADRC is safe in this phase 1 study with a 12-month follow-up.


Assuntos
Tecido Adiposo/transplante , Terapia Baseada em Transplante de Células e Tecidos/métodos , Disfunção Erétil , Prostatectomia/efeitos adversos , Idoso , Disfunção Erétil/diagnóstico , Disfunção Erétil/etiologia , Disfunção Erétil/terapia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Medicina Regenerativa/métodos , Células Estromais/transplante , Resultado do Tratamento
18.
Stem Cells Transl Med ; 6(8): 1666-1672, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28653440

RESUMO

Breast cancer-related lymphedema (BCRL) is a debilitating late complication with a lack of treatment opportunities. Recent studies have suggested that mesenchymal stromal cells can alleviate lymphedema. Herein, we report the results from the first human pilot study with freshly isolated adipose-derived regenerative cells (ADRC) for treating lymphedema with 6 months follow-up. Ten BCRL patients were included. ADRC was injected directly into the axillary region, which was combined with a scar-releasing fat graft procedure. Primary endpoints were change in arm volume. Secondary endpoints were change in patient reported outcome and safety. The study is registered with ClinicalTrials.gov (NCT02592213). During follow-up, a small volume reduction was noted but was not significant. Five patients reduced their use of conservative management. Patient-reported outcomes improved significantly over time. ADRCs were well tolerated and only minor transient adverse events related to liposuction were noted. In this pilot study, a single injection of ADRC improved lymphedema based on patient-reported outcome measures, and there were no serious adverse events in the 6 months follow-up period. In addition, half of the patients reduced their use of conservative management. ADRC therapy is a promising interventional therapy for alleviating lymphedema, but results need to be confirmed in randomized clinical trials. Stem Cells Translational Medicine 2017;6:1666-1672.


Assuntos
Tecido Adiposo/citologia , Linfedema Relacionado a Câncer de Mama/terapia , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Tecidos/métodos , Tecido Adiposo/transplante , Adulto , Idoso , Células Cultivadas , Estudos de Viabilidade , Feminino , Humanos , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Pessoa de Meia-Idade , Transplante de Tecidos/efeitos adversos
19.
Stem Cells Transl Med ; 6(9): 1786-1794, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28722289

RESUMO

The popularity of adipose-derived cell therapy has increased over the last decade, and the number of studies published annually is growing. However, concerns regarding safety in the setting of previous malignancy or the use of allogeneic cells have been raised. We therefore aimed to systematically review all clinical studies using adipose-derived cell therapy to identify reported adverse events with a special focus on risk of thromboembolic, immunological, and oncological safety concerns. Our systematic search resulted in 70 included studies involving more than 1,400 patients that were treated with adipose-derived cell therapy. Safety assessment method was not described in 32 of the included studies. For studies involving systemic or cardiac administration, one case of pulmonary thromboembolism and cases of both myocardial and cerebral infarctions were described. In the setting of allogeneic cell therapy studies, where the production of specific antibodies toward donor cells was examined, it was noted that 19%-34% of patients develop antibodies, but the consequence of this is unknown. With regard to oncological safety, only one case of breast cancer recurrence was identified out of 121 patients. Adipose-derived cell therapy has so far shown a favorable safety profile, but safety assessment description has, in general, been of poor quality, and only adverse events that are looked for will be found. We encourage future studies to maintain a strong focus on the safety profile of cell therapy, so its safeness can be confirmed. Stem Cells Translational Medicine 2017;6:1786-1794.


Assuntos
Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Humanos , Transplante de Células-Tronco Mesenquimais/métodos
20.
Int J Biol Macromol ; 97: 460-467, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28099888

RESUMO

Delta-like 1 homolog (DLK1) is an imprinted gene, which is widely expressed during mammalian development and plays a pivotal role in differentiation of various tissue types. Most recently, we have shown that DLK1 interacts with NOTCH1, yet several Notch independent mechanisms have previously been suggested as well, but only poorly confirmed in a mammalian context. In the present study, we employed the mammalian two-hybrid (MTH) system, a genetic in vivo protein-protein interaction system, to show robust DLK1-DLK1, DLK1-FnI (Fibronectin) and DLK1-CFR (cysteine-rich FGF receptor) interactions, whereas the proposed DLK1-IGFBP1 interaction was not supported by MTH. Very little has previously been described on the DLK1 self-interaction. Herein, we showed by immunoprecipitation as well as Sulfo-SBED label transfer that the DLK1-DLK1 interaction likely is part of Dlk1's function in preadipocytes. Furthermore our data suggest that DLK1 interacts with itself through EGF domain 4 and 5, which is distinct from the recently described NOTCH1-DLK1 interaction, which occurs between EGF domain 5 and 6. This opens up the possibility that Notch independent mechanisms like the DLK1-DLK1 interaction may modulate the non-canonical NOTCH1-DLK1 interaction further complexing this system.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas de Membrana/metabolismo , Agregados Proteicos , Receptor Notch1/metabolismo , Animais , Proteínas de Ligação ao Cálcio , Fibronectinas/metabolismo , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/química , Ligantes , Proteínas de Membrana/química , Camundongos , Células NIH 3T3 , Ligação Proteica , Domínios Proteicos , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais
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