{"id":7927,"date":"2026-04-03T09:37:54","date_gmt":"2026-04-03T09:37:54","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/jip-beugels\/"},"modified":"2026-04-23T09:09:22","modified_gmt":"2026-04-23T09:09:22","slug":"jip-beugels","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/jip-beugels\/","title":{"rendered":"Jip Beugels"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":14226,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-7927","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"naam_van_het_proefschift":"Stem cells in plastic and regenerative surgery","samenvatting":"Hoofdstuk 1. Algemene introductie\n\nIn plastische en reconstructieve chirurgie zijn een groot aantal chirurgische procedures ontwikkeld om vorm en\/of functie te herstellen. Autologe vet transfer (AFT), waarbij vet van de ene locatie naar de andere wordt gebracht is een recent voorbeeld dat zowel veilig als veelzijdig is. Een belangrijk aspect voor het uiteindelijke resultaat is de status van het lokale micromilieu in het regenererende weefsel. Hoe fantastisch de chirurg of de chirurgische techniek ook is, zij hebben geen directe mogelijkheid om het lokale micromilieu zodanig te be\u00efnvloeden dat het de genezing bevordert. Het inzetten van stamcellen vertoont op dit vlak grote potentie. Deze thesis onderzocht het effect van stamcellen op twee belangrijke cellulaire processen die optreden na (chirurgisch) trauma: inflammatie en angiogenese. Idealiter zouden we een techniek wensen om direct de reeds aanwezige stamcellen in het weefsel te \u201cactiveren\u201d en ze te stimuleren om angiogenese te bevorderen of inflammatie te moduleren. Een techniek genaamd elektrische stimulatie is veelbelovend voor deze indicatie.\n\nHoofdstuk 2. Effectiviteit en veiligheid van autologe vet transfer in faciale plastische chirurgie: een systematische review en meta-analyse.\n\nIn hoofdstuk 2 focusten we specifiek op AFT door een grondige analyse van de effectiviteit en veiligheid van AFT in plastische chirurgie. We compileerden de beschikbare klinische data van 52 relevante studies die in totaal bestonden uit 1568 unieke pati\u00ebnten in een systematische review en meta-analyse. Het tevredenheidsniveau bleek algemeen erg hoog te zijn met 91.1% in de pati\u00ebntengroep en 88.6% bij de chirurgen. Het gemiddeld aantal sessies om het gewenste eindresultaat te bereiken was 1.5, met een retentiepercentage van 50-60% van het ingebrachte vetweefsel. Lichte complicaties traden op in minder dan 5% van de gevallen, waaruit geconcludeerd werd dat AFT in het gelaat een veilige ingreep is.\n\nHoofdstuk 3. Autologe vet transfer als een behandeling voor perifere neuropathische pijn zonder duidelijke oorzaak.\n\nIn hoofdstuk 3 onderzochten we in een klinische trial of pati\u00ebnten met chronische neuropathische pijn zonder oorzaak zoals een neuroom, en die reeds alle andere mogelijkheden voor behandeling hadden geprobeerd, effect zouden hebben van AFT op het verminderen van de pijn. Veertien pati\u00ebnten ontvingen AFT in het gebied van de aangedane zenuw. Tot de uitkomstparameters behoorden pati\u00ebnttevredenheid, pijn gescoord op een visuele analoge schaal (VAS) en de kwaliteit van slaap. De pati\u00ebnttevredenheid bedroeg 93% bij de controle na 2 weken en 86% na een follow-up van meer dan \u00e9\u00e9n jaar. De gemiddelde VAS score daalde significant van 7.4 voor de ingreep tot 3.8 direct na AFT en 4.3 bij de controle op lange termijn. De kwaliteit van slaap verbeterde in 50% van de pati\u00ebnten, waarbij de rest aangaf geen verschil te merken. Er werden geen complicaties geregistreerd. Deze studie toont dat AFT een mogelijke optie kan zijn in de behandeling van pati\u00ebnten die lijden aan therapieresistente neuropathische pijn. Een potentieel werkingsmechanisme hiervan kan liggen in de regeneratieve eigenschappen van cellen in het vettransplantaat.\n\nHoofdstuk 4. Infusie met gestandaardiseerde uit beenmerg verkregen stamcellen verbetert de overleving en het herstel in een ratmodel van dwarslaesie.\n\nIn hoofdstuk 4 hebben we de immunomodulatoire eigenschappen van een geraffineerd preparaat met mesenchymale en hematopo\u00efetische stamcellen uit beenmerg onderzocht in een acuut model van dwarslaesie. Onze focus lag bij het onderzoeken van de anti-inflammatoire eigenschappen en het effect op zenuwregeneratie in de context van een verbeterde functionele uitkomst. Hiervoor kregen T-cel defici\u00ebnte ratten, bij wie een dwarslaesie was aangebracht door middel van balloncompressie, een intrathecale injectie met uit beenmerg verkregen stamcellen (genaamd Neuro-Cells; NC) de dag na de dwarslaesie. Gedurende de eerste 5 weken na de interventie verbeterden NC het motorische herstel significant en veroorzaakten zij minder trauma gerelateerde complicaties in vergelijking met de controle groep die behandeld was met alleen oplosvloeistof. Histologische analyses toonden aan dat NC astrogliose en apoptose vooral in de eerste dagen na toediening verminderden. Proteomisch onderzoek van het verzamelde ruggenmerg aan het einde van de studie (na 56 dagen) wees op vrijgelaten paracriene factoren en identificeerde eiwitten betrokken bij regeneratieve processen.","summary":"In plastic and reconstructive surgery many surgical procedures have been developed to restore form and\/or function. Autologous fat transfer (AFT), in which adipose tissue is relocated from one place to the other is a recent example that is safe and versatile. An important aspect in the final outcome for the patient is the state of the local microenvironment in the regenerating tissue. However great the surgeon or surgical technique may be, they have no direct way of modifying the local microenvironment to promote healing. Great potential herein lies with the use of (adult) stem cells. This thesis investigated the effect of stem cells on two important cellular processes, occurring after (surgical) tissue trauma: inflammation and angiogenesis. Ideally we would have a technique to directly \u201cactivate\u201d tissue resident stem cells and guide them towards promoting angiogenesis or modulating inflammation. A technique called electrical stimulation is promising in this area.\n\nChapter 2. Efficacy and safety of autologous fat transfer in facial reconstructive surgery: a systematic review and meta-analysis.\n\nIn chapter 2, we focused specifically on AFT through analysis of the efficacy and safety of performing AFT in plastic surgery. We compiled the available clinical data from 52 relevant studies consisting of 1568 unique patients in a systematic review and meta-analysis. It showed a very high overall satisfaction rate of 91.1% in patients, together with a 88.6% satisfaction rate in surgeons. In facial reconstructive surgery the mean number of sessions to achieve the desired end result was 1.5, with a retention rate of 50-60% of the grafted material. Less than 5% of the procedures resulted in minor complications, deeming it a safe procedure.\n\napparent cause.\n\nIn chapter 3, we tested in a clinical trial whether patients in a chronic neuropathic pain setting without a cause such as a neuroma, and who had exhausted all other treatment options, would benefit from AFT with respect to their pain perception. Fourteen patients received AFT in the area of the affected nerve. Outcome parameters included patient satisfaction, pain scored on a visual analogue scale (VAS) and quality of sleep. Patient satisfaction was 93% at the follow-up after two weeks and 86% after a follow-up of more than one year. The mean VAS score decreased significantly from 7.4 before surgery to 3.8 directly after AFT and 4.3 at long-term follow-up visit. The quality of sleep improved in 50% of the patients, whereas the remainder indicated no difference. No complications were registered. This study shows that AFT can be a suitable option for patients suffering from debilitating neuropathic pain that is refractory to other treatments. A potential mechanism of action lies in the regenerative capabilities of cells within the transplant.\n\nChapter 4. Standardized human bone marrow-derived stem cells infusion improves survival and recovery in a rat model of spinal cord injury.\n\nIn chapter 4, we set out to investigate the immunomodulatory properties of a refined bone-marrow derived preparation of mesenchymal and hematopoietic stem cells in an acute model of spinal cord injury. Our focus lay towards researching the anti-inflammatory properties and the effect on nerve regeneration in the context of improved functional outcome. To this end T-cell deficient rats, in which a spinal cord lesion (SCI) was induced by balloon-compression of the spinal cord, received an intrathecal injection of bone marrow-derived stem cells (called Neuro-Cells; NC) the day after SCI. During the first 5 weeks after this intervention, NC significantly improved locomotor recovery and induced less injury-associated adverse events compared to the vehicle-treated control group. Histological analyses showed that NC reduced astrogliosis and apoptosis primarily in the first days after administration. Proteomic studies of the sampled spinal cords at the study endpoint (56 days) pointed to the release of paracrine factors and identified proteins involved in regenerative processes.\n\ntransplantation on angiogenesis in a rat model with hind limb ischemia.\n\nIn chapter 5, we surgically ligated the external iliac artery of T-cell deficient rats to develop a hind limb ischemia model. The surgical ligation of arterial blood vessels lead to an acute-onset moderate to severe traumatic ischemia in the affected hind limbs. After 7 days a baseline digital subtraction angiography (DSA) was made. Then, different doses of human bone marrow-derived stem cells, or vehicle alone were administered intramuscularly and intra-arterially. At day 35, DSA was repeated and images were compared between the groups at the different time points to directly visualize the angiogenic effects of the administered stem cells. Comparison of DSA Mean Gray Values at day 35 versus day 7 showed a significant increase in the low and medium dose groups, pointing towards improved vascularization, whereas the vehicle group displayed a natural decrease. Surprisingly, the high dose stem cell group also had a decreased Mean Gray Value at day 35 and more tissue damage, possibly due to hyperviscosity. A dose response could not be detected.\n\nChapter 6. Electrical stimulation promotes the angiogenic potential of adipose-derived stem cells.\n\nIn chapter 6, we electrically stimulated adipose tissue-derived stem cells (ASC) in vitro to determine the effects of electrical stimulation (ES) on the angiogenic potential of ASC. Cultured human ASC were electrically stimulated for 72 hours after which the medium of stimulated (ES) and non-stimulated (control) ASC was analyzed for angiogenesis-related proteins by protein array and ELISA. Nine angiogenesis-related proteins were detected in the medium of electrically stimulated ASC. The pro-angiogenic proteins VEGF and MCP-1 were significantly increased following ES compared to controls, while the anti-angiogenic factor Serpin E1\/PAI-1 was significantly decreased. Despite increased levels of anti-angiogenic TSP-1 and TIMP-1, medium of ES-treated ASC significantly increased vessel density, total vessel network length and branching points in a functional in vivo model of angiogenesis, called a chorio-allantoic membrane assay. This proof-of-concept study showed that ES increased the angiogenic potential of ASC both in vitro and in vivo and lays the foundation for further translational studies.\n\nThe general discussion reflects on the findings of the individual studies included in this thesis, starting with autologous fat transfer. Next chapters 4 through 6 were discussed in light of the topics immunomodulation and angiogenesis. Gaps in current knowledge are identified and proposals for future studies are provided.","auteur":"Jip Beugels","auteur_slug":"jip-beugels","publicatiedatum":"16 september 2020","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/jipbeugels?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202604030934","isbn":"978-94-6380-941-2","doi_nummer":"","naam_universiteit":"Universiteit Maastricht","afbeeldingen":14226,"naam_student:":"","binnenwerk":"","universiteit":"Universiteit Maastricht","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/7927","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=7927"}],"version-history":[{"count":1,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/7927\/revisions"}],"predecessor-version":[{"id":7930,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/7927\/revisions\/7930"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/14226"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=7927"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=7927"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}