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The Potential of Dental Pulp Stromal Cells and Their Derivatives for Angiogenesis and Cancer Therapy
No full textStem cells have extensively been studied during the last decades as potential
therapeutics in diverse disease models, including tissue regeneration and cancer.
The most popular stem cell type is the mesenchymal stromal cell (MSC), which
can be isolated from various foetal and adult tissues and is characterized by
differentiation towards multiple functional mature cell types, including adipocytes,
chondrocytes and osteocytes. Although most researchers use MSCs derived from
the bone marrow (BM-MSCs), their clinical potential is compromised by their
invasive and painful isolation. In contrast, dental pulp stromal cells (DPSCs) can
easily be isolated from the central tooth pulp and express better proliferation and
immunomodulatory capacities. Nevertheless, information on the therapeutic
potential of this MSC subtype in tissue engineering and cancer is scarce, which
was the topic of this dissertation.
Tissue regeneration requires the fast blood supply of newly formed tissues by the
process of angiogenesis. This multistep neovascularization process consists of
extracellular matrix degradation, endothelial cell proliferation, migration and tube
formation, vessel maturation and stabilization. Proangiogenic properties have
previously been assigned to both BM-MSCs and DPSCs. Despite their broad
differentiation potential, these effects are mainly mediated by paracrine secreted
factors. This secretome, collected as conditioned medium (CM), consists of both
soluble factors and nanoscale membrane-bound extracellular vesicles (EVs). In
contrast to the short half-life associated with free molecules, EV-encapsulated
proteins and miRNAs are better protected against enzymatic digestion, which
could improve their therapeutic efficacy in the human body. Recent studies
indicate the essential role of these EV-associated factors in the proangiogenic
capacity of BM-MSCs. Therefore, this dissertation studied the potential of DPSC
EVs as beneficial alternative for whole stem cell therapy to induce angiogenesis
and eventual tissue regeneration. The relative contribution of soluble factors
versus EVs to the paracrine angiogenic properties of DPSCs was studied and
compared with those of BM-MSCs (Chapter II). Numerous pro- and antiangiogenic factors were detected in complete CM, EV-depleted CM and EVs. All
these fractions significantly induced in vitro endothelial cell migration.
Nevertheless, the protein concentrations and functional effects were stronger for
CM compared to EVs, while no influence of EV depletion of the CM was observed. In addition, the chemotactic response and particle secretion were higher in case
of BM-MSCs compared to DPSCs. Furthermore, the effect of BM-MSC and DPSC
CM and EVs was validated in vivo in the chicken chorioallantoic membrane (CAM)
assay. This in vivo angiogenic model using the strongly vascularized and fast
developing extraembryonic membrane of the chicken embryo has proven its
added value in the tissue engineering field as a fast, cheap and straightforward
pre-screening tool for the angiogenic properties of growth factors, (stem) cells
and scaffolds (Chapter III). BM-MSC CM, but not DPSC CM nor EVs, induced
blood vessel formation in the CAM assay. Our study suggested superior paracrine
angiogenic properties and eventual tissue regenerative capacity for BM-MSCs.
Moreover, the complete secretome seems preferable in clinical regenerative
medicine given the limited angiogenic effects of EVs and the high workload
required to isolate and characterize pure EVs.
Besides their therapeutic potential for tissue regeneration, MSCs could offer
promising opportunities in the cancer research field due to their specific tumour
homing capacity. Cancer is globally the second leading cause of death, after
cardiovascular diseases, caused by the limited specificity and efficacy of current
therapies. The tumour tropism of MSCs might be exploited to specifically deliver
anti-cancer therapeutics to the tumour, resulting in lower effective doses and less
adverse systemic side-effects. This dissertation investigated the relatively
unexplored tumour homing of DPSCs and their effect on tumour growth and
angiogenesis, since the influence of other MSC subtypes on tumour
aggressiveness has described to be controversial (Chapter IV). Our study showed
the in vitro tumour-dependent homing of DPSCs towards human head and neck
squamous cell carcinoma (HNSCC) and mouse melanoma cell lines, with no
migration towards a human breast adenocarcinoma cell line. This tumour tropism
could not be confirmed in an in vivo HNSCC xenograft mouse model after
intravenous, intraperitoneal or peritumoural DPSC injection. Nevertheless,
intratumourally administered stem cells survived for at least two weeks in the
tumour microenvironment with no adverse effects on tumour growth, morphology
and angiogenesis. While further studies should focus on the optimization of the
experimental set-up to improve in vivo stem cell tumour homing, our data offer a first promising indication for the safe use of direct intratumourally injected DPSCs
as potential delivery modes of anti-cancer therapeutics to treat HNSCC.
In conclusion, this dissertation showed the therapeutic opportunities that DPSCs
and their derivatives could offer in the tissue engineering and cancer research
field. Further long-term in vivo studies should focus on the optimization of the
experimental set-up to maximize the efficiency and safety of DPSC-based
therapies.Stamcellen zijn de afgelopen decennia uitvoerig bestudeerd als potentiële therapie
in diverse ziektebeelden, waaronder weefselregeneratie en kanker. Het
populairste stamceltype is de mesenchymale stromale cel (MSC), die geïsoleerd
kan worden uit diverse foetale en adulte weefsels en gekenmerkt wordt door zijn
differentiatie naar meerdere mature functionele celtypes, zoals vetcellen,
kraakbeencellen en botcellen. Hoewel de meeste wetenschappers onderzoek doen
naar MSCs uit het beenmerg (BM-MSCs), is het klinisch potentieel van deze
stamcellen beperkt door hun invasieve en pijnlijke isolatie. Dentale pulpa stromale
cellen (DPSCs) kunnen daarentegen eenvoudig geïsoleerd worden uit de centrale
tandpulpa en vertonen betere proliferatie en immuunmodulerende
eigenschappen. Desondanks is er nog weinig gekend over de therapeutische
mogelijkheden van dit MSC subtype in weefselregeneratie en kanker, wat het
onderwerp vormde van dit proefschrift.
Weefselregeneratie vereist een snelle vorming van bloedvaten, ook wel
angiogenese genoemd, die nodig is voor de toevoer van zuurstof naar de
nieuwgevormde weefsels. Angiogenese bestaat uit meerdere stappen, namelijk
afbraak van de omliggende extracellulaire matrix, vervolgens proliferatie, migratie
en tubevorming van endotheelcellen en tenslotte stabilisatie van de bloedvaten
na rekrutering van pericyten. Pro-angiogene eigenschappen zijn reeds eerder
aangetoond voor zowel BM-MSCs als DPSCs. Beide celtypes kunnen de
bloedvatvorming induceren door paracrien gesecreteerde factoren. Dit secretoom,
gecollecteerd als geconditioneerd medium (CM), bevat zowel opgeloste factoren
als ultrakleine membraangebonden extracellulaire vesikels (EVs). In tegenstelling
tot de korte halfwaardetijd geassocieerd met vrije moleculen, zijn de eiwitten en
miRNAs ingekapseld in EVs beter beschermd tegen enzymatische digestie, wat
hun therapeutische werking in het menselijk lichaam kan verhogen. Recente
studies wijzen op een essentiële rol van deze EV-geassocieerde factoren in de proangiogene capaciteit van BM-MSCs. Het doel van dit proefschrift was daarom om
te onderzoeken of DPSC EVs een gunstig alternatief kunnen bieden voor de
klassieke MSC therapie in angiogenese. De relatieve bijdrage van opgeloste
factoren versus EVs in de paracriene angiogene eigenschappen van DPSCs werd
bepaald en vergeleken met deze van BM-MSCs (Hoofdstuk II). Vele pro- en antiangiogene factoren waren aanwezig in volledig CM, EV-arm CM en EVs. Hoewel in vitro endotheelcelmigratie geïnduceerd werd door alle fracties, lagen de
eiwitconcentraties hoger en waren de functionele effecten sterker bij het CM ten
opzichte van de EVs. Bovendien had EV depletie geen invloed op het angiogeen
profiel van het CM. Daarnaast was er ook een significant verschil tussen beide
stamceltypes met meer endotheelcelmigratie en partikelsecretie voor BM-MSCs.
De bloedvatvorming werd ook bestudeerd in het kip chorioallantoic membraan
(CAM) assay. Dit sterk gevasculariseerde en snel ontwikkelende extra-embryonaal
membraan van het kippenembryo heeft zijn meerwaarde als snelle, goedkope en
eenvoudige in vivo pre-screening methode voor de angiogene eigenschappen van
groeifactoren, (stam)cellen en scaffolds reeds uitvoerig bewezen (Hoofdstuk
III). BM-MSC CM, maar niet DPSCs of EVs, kon bloedvatvorming induceren in de
CAM assay. Deze data suggereren superieure paracriene angiogene en
regeneratieve eigenschappen voor BM-MSCs. Bovendien is gebruik van het
volledige secretoom aangeraden in klinische regeneratieve geneeskunde omwille
van de beperkte angiogene effecten van EVs en de hoge werkdruk en kosten die
gepaard gaan met de isolatie en karakterisatie van zuivere EVs.
Naast hun therapeutisch potentieel in weefselregeneratie kunnen MSCs ook
interessante mogelijkheden bieden in kankeronderzoek dankzij hun eigenschap
om specifiek naar tumoren te migreren (ook tumortropisme genoemd). Omwille
van de beperkte specificiteit en efficiëntie van de huidige therapieën blijft kanker
wereldwijd de belangrijkste doodsoorzaak, na cardiovasculaire ziektes. Het
tumortropisme van MSCs kan benut worden voor het specifiek aanleveren van
anti-kankertherapie in de tumor met lagere effectieve dosissen en minder
systemische neveneffecten tot gevolg. Deze doctoraatsthesis onderzocht het
ongekende tumortropisme van DPSCs en hun invloed op tumorgroei en
angiogenese, aangezien controversiële effecten op tumor agressiviteit eerder zijn
aangetoond voor andere MSC subtypes (Hoofdstuk IV). In vitro migreerden
DPSCs enkel naar humane hoofd en nek plaveiselcelcarcinoom (HNSCC) en muis
melanoom cellijnen en niet naar een humane borstadenocarcinoom cellijn. Deze
migratie kon niet bevestigd worden in een in vivo HNSCC xenograft muismodel na
intraveneuze, intraperitoneale of peritumorale stamcelinjectie. Intratumoraal
toegediende DPSCs overleefden gedurende minstens twee weken in het tumor
micromilieu zonder nadelige effecten op tumorgroei, morfologie en angiogenese. Hoewel de experimentele set-up verder geoptimaliseerd moet worden in
toekomstige studies om in vivo stamcelmigratie naar tumoren te verbeteren,
bieden onze data een eerste veelbelovende indicatie voor het veilig gebruik van
intratumoraal geïnjecteerde DPSCs als aanhoudende bron van anti-kanker
medicatie voor de behandeling van HNSCC.
Ter conclusie, dit proefschrift toont aan dat DPSCs en hun derivaten vele
therapeutische mogelijkheden kunnen bieden voor weefselregeneratie en kanker.
Bijkomend onderzoek in langtermijn preklinische studies is essentieel om de
efficiëntie en veiligheid van DPSC-gebaseerde therapieën verder te optimaliseren
The Potential of Dental Pulp Stromal Cells and Their Derivatives for Angiogenesis and Cancer Therapy
No full textStem cells have extensively been studied during the last decades as potential
therapeutics in diverse disease models, including tissue regeneration and cancer.
The most popular stem cell type is the mesenchymal stromal cell (MSC), which
can be isolated from various foetal and adult tissues and is characterized by
differentiation towards multiple functional mature cell types, including adipocytes,
chondrocytes and osteocytes. Although most researchers use MSCs derived from
the bone marrow (BM-MSCs), their clinical potential is compromised by their
invasive and painful isolation. In contrast, dental pulp stromal cells (DPSCs) can
easily be isolated from the central tooth pulp and express better proliferation and
immunomodulatory capacities. Nevertheless, information on the therapeutic
potential of this MSC subtype in tissue engineering and cancer is scarce, which
was the topic of this dissertation.
Tissue regeneration requires the fast blood supply of newly formed tissues by the
process of angiogenesis. This multistep neovascularization process consists of
extracellular matrix degradation, endothelial cell proliferation, migration and tube
formation, vessel maturation and stabilization. Proangiogenic properties have
previously been assigned to both BM-MSCs and DPSCs. Despite their broad
differentiation potential, these effects are mainly mediated by paracrine secreted
factors. This secretome, collected as conditioned medium (CM), consists of both
soluble factors and nanoscale membrane-bound extracellular vesicles (EVs). In
contrast to the short half-life associated with free molecules, EV-encapsulated
proteins and miRNAs are better protected against enzymatic digestion, which
could improve their therapeutic efficacy in the human body. Recent studies
indicate the essential role of these EV-associated factors in the proangiogenic
capacity of BM-MSCs. Therefore, this dissertation studied the potential of DPSC
EVs as beneficial alternative for whole stem cell therapy to induce angiogenesis
and eventual tissue regeneration. The relative contribution of soluble factors
versus EVs to the paracrine angiogenic properties of DPSCs was studied and
compared with those of BM-MSCs (Chapter II). Numerous pro- and antiangiogenic factors were detected in complete CM, EV-depleted CM and EVs. All
these fractions significantly induced in vitro endothelial cell migration.
Nevertheless, the protein concentrations and functional effects were stronger for
CM compared to EVs, while no influence of EV depletion of the CM was observed. In addition, the chemotactic response and particle secretion were higher in case
of BM-MSCs compared to DPSCs. Furthermore, the effect of BM-MSC and DPSC
CM and EVs was validated in vivo in the chicken chorioallantoic membrane (CAM)
assay. This in vivo angiogenic model using the strongly vascularized and fast
developing extraembryonic membrane of the chicken embryo has proven its
added value in the tissue engineering field as a fast, cheap and straightforward
pre-screening tool for the angiogenic properties of growth factors, (stem) cells
and scaffolds (Chapter III). BM-MSC CM, but not DPSC CM nor EVs, induced
blood vessel formation in the CAM assay. Our study suggested superior paracrine
angiogenic properties and eventual tissue regenerative capacity for BM-MSCs.
Moreover, the complete secretome seems preferable in clinical regenerative
medicine given the limited angiogenic effects of EVs and the high workload
required to isolate and characterize pure EVs.
Besides their therapeutic potential for tissue regeneration, MSCs could offer
promising opportunities in the cancer research field due to their specific tumour
homing capacity. Cancer is globally the second leading cause of death, after
cardiovascular diseases, caused by the limited specificity and efficacy of current
therapies. The tumour tropism of MSCs might be exploited to specifically deliver
anti-cancer therapeutics to the tumour, resulting in lower effective doses and less
adverse systemic side-effects. This dissertation investigated the relatively
unexplored tumour homing of DPSCs and their effect on tumour growth and
angiogenesis, since the influence of other MSC subtypes on tumour
aggressiveness has described to be controversial (Chapter IV). Our study showed
the in vitro tumour-dependent homing of DPSCs towards human head and neck
squamous cell carcinoma (HNSCC) and mouse melanoma cell lines, with no
migration towards a human breast adenocarcinoma cell line. This tumour tropism
could not be confirmed in an in vivo HNSCC xenograft mouse model after
intravenous, intraperitoneal or peritumoural DPSC injection. Nevertheless,
intratumourally administered stem cells survived for at least two weeks in the
tumour microenvironment with no adverse effects on tumour growth, morphology
and angiogenesis. While further studies should focus on the optimization of the
experimental set-up to improve in vivo stem cell tumour homing, our data offer a first promising indication for the safe use of direct intratumourally injected DPSCs
as potential delivery modes of anti-cancer therapeutics to treat HNSCC.
In conclusion, this dissertation showed the therapeutic opportunities that DPSCs
and their derivatives could offer in the tissue engineering and cancer research
field. Further long-term in vivo studies should focus on the optimization of the
experimental set-up to maximize the efficiency and safety of DPSC-based
therapies.Stamcellen zijn de afgelopen decennia uitvoerig bestudeerd als potentiële therapie
in diverse ziektebeelden, waaronder weefselregeneratie en kanker. Het
populairste stamceltype is de mesenchymale stromale cel (MSC), die geïsoleerd
kan worden uit diverse foetale en adulte weefsels en gekenmerkt wordt door zijn
differentiatie naar meerdere mature functionele celtypes, zoals vetcellen,
kraakbeencellen en botcellen. Hoewel de meeste wetenschappers onderzoek doen
naar MSCs uit het beenmerg (BM-MSCs), is het klinisch potentieel van deze
stamcellen beperkt door hun invasieve en pijnlijke isolatie. Dentale pulpa stromale
cellen (DPSCs) kunnen daarentegen eenvoudig geïsoleerd worden uit de centrale
tandpulpa en vertonen betere proliferatie en immuunmodulerende
eigenschappen. Desondanks is er nog weinig gekend over de therapeutische
mogelijkheden van dit MSC subtype in weefselregeneratie en kanker, wat het
onderwerp vormde van dit proefschrift.
Weefselregeneratie vereist een snelle vorming van bloedvaten, ook wel
angiogenese genoemd, die nodig is voor de toevoer van zuurstof naar de
nieuwgevormde weefsels. Angiogenese bestaat uit meerdere stappen, namelijk
afbraak van de omliggende extracellulaire matrix, vervolgens proliferatie, migratie
en tubevorming van endotheelcellen en tenslotte stabilisatie van de bloedvaten
na rekrutering van pericyten. Pro-angiogene eigenschappen zijn reeds eerder
aangetoond voor zowel BM-MSCs als DPSCs. Beide celtypes kunnen de
bloedvatvorming induceren door paracrien gesecreteerde factoren. Dit secretoom,
gecollecteerd als geconditioneerd medium (CM), bevat zowel opgeloste factoren
als ultrakleine membraangebonden extracellulaire vesikels (EVs). In tegenstelling
tot de korte halfwaardetijd geassocieerd met vrije moleculen, zijn de eiwitten en
miRNAs ingekapseld in EVs beter beschermd tegen enzymatische digestie, wat
hun therapeutische werking in het menselijk lichaam kan verhogen. Recente
studies wijzen op een essentiële rol van deze EV-geassocieerde factoren in de proangiogene capaciteit van BM-MSCs. Het doel van dit proefschrift was daarom om
te onderzoeken of DPSC EVs een gunstig alternatief kunnen bieden voor de
klassieke MSC therapie in angiogenese. De relatieve bijdrage van opgeloste
factoren versus EVs in de paracriene angiogene eigenschappen van DPSCs werd
bepaald en vergeleken met deze van BM-MSCs (Hoofdstuk II). Vele pro- en antiangiogene factoren waren aanwezig in volledig CM, EV-arm CM en EVs. Hoewel in vitro endotheelcelmigratie geïnduceerd werd door alle fracties, lagen de
eiwitconcentraties hoger en waren de functionele effecten sterker bij het CM ten
opzichte van de EVs. Bovendien had EV depletie geen invloed op het angiogeen
profiel van het CM. Daarnaast was er ook een significant verschil tussen beide
stamceltypes met meer endotheelcelmigratie en partikelsecretie voor BM-MSCs.
De bloedvatvorming werd ook bestudeerd in het kip chorioallantoic membraan
(CAM) assay. Dit sterk gevasculariseerde en snel ontwikkelende extra-embryonaal
membraan van het kippenembryo heeft zijn meerwaarde als snelle, goedkope en
eenvoudige in vivo pre-screening methode voor de angiogene eigenschappen van
groeifactoren, (stam)cellen en scaffolds reeds uitvoerig bewezen (Hoofdstuk
III). BM-MSC CM, maar niet DPSCs of EVs, kon bloedvatvorming induceren in de
CAM assay. Deze data suggereren superieure paracriene angiogene en
regeneratieve eigenschappen voor BM-MSCs. Bovendien is gebruik van het
volledige secretoom aangeraden in klinische regeneratieve geneeskunde omwille
van de beperkte angiogene effecten van EVs en de hoge werkdruk en kosten die
gepaard gaan met de isolatie en karakterisatie van zuivere EVs.
Naast hun therapeutisch potentieel in weefselregeneratie kunnen MSCs ook
interessante mogelijkheden bieden in kankeronderzoek dankzij hun eigenschap
om specifiek naar tumoren te migreren (ook tumortropisme genoemd). Omwille
van de beperkte specificiteit en efficiëntie van de huidige therapieën blijft kanker
wereldwijd de belangrijkste doodsoorzaak, na cardiovasculaire ziektes. Het
tumortropisme van MSCs kan benut worden voor het specifiek aanleveren van
anti-kankertherapie in de tumor met lagere effectieve dosissen en minder
systemische neveneffecten tot gevolg. Deze doctoraatsthesis onderzocht het
ongekende tumortropisme van DPSCs en hun invloed op tumorgroei en
angiogenese, aangezien controversiële effecten op tumor agressiviteit eerder zijn
aangetoond voor andere MSC subtypes (Hoofdstuk IV). In vitro migreerden
DPSCs enkel naar humane hoofd en nek plaveiselcelcarcinoom (HNSCC) en muis
melanoom cellijnen en niet naar een humane borstadenocarcinoom cellijn. Deze
migratie kon niet bevestigd worden in een in vivo HNSCC xenograft muismodel na
intraveneuze, intraperitoneale of peritumorale stamcelinjectie. Intratumoraal
toegediende DPSCs overleefden gedurende minstens twee weken in het tumor
micromilieu zonder nadelige effecten op tumorgroei, morfologie en angiogenese. Hoewel de experimentele set-up verder geoptimaliseerd moet worden in
toekomstige studies om in vivo stamcelmigratie naar tumoren te verbeteren,
bieden onze data een eerste veelbelovende indicatie voor het veilig gebruik van
intratumoraal geïnjecteerde DPSCs als aanhoudende bron van anti-kanker
medicatie voor de behandeling van HNSCC.
Ter conclusie, dit proefschrift toont aan dat DPSCs en hun derivaten vele
therapeutische mogelijkheden kunnen bieden voor weefselregeneratie en kanker.
Bijkomend onderzoek in langtermijn preklinische studies is essentieel om de
efficiëntie en veiligheid van DPSC-gebaseerde therapieën verder te optimaliseren
Safety and Homing of Human Dental Pulp Stromal Cells in Head and Neck Cancer
No full textBACKGROUND: Head and neck cancer (HNC) is one of the most common cancers, associated with a huge mortality and morbidity. In order to improve patient outcomes, more efficient and targeted therapies are essential. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) express tumour homing capacity, which could be exploited to target anti-cancer drug delivery to the tumour region and reduce adverse side-effects. Nevertheless, dental pulp stromal cells (DPSCs), an MSC-like population present in teeth, could offer important clinical benefits because of their easy isolation and superior proliferation compared to BM-MSCs. Therefore, we aimed to elucidate the tumour homing and safe usage of DPSCs to treat HNC. METHODS: The in vivo survival as well as the effect of intratumourally administered DPSCs on tumour aggressiveness was tested in a HNC xenograft mouse model by using bioluminescence imaging (BLI), (immuno)histology and qRT-PCR. Furthermore, the in vitro and in vivo tumour homing capacity of DPSCs towards a HNC cell line were evaluated by a transwell migration assay and BLI, respectively. RESULTS: Intratumourally injected DPSCs survived for at least two weeks in the tumour micro-environment and had no significant influence on tumour morphology, growth, angiogenesis and epithelial-to-mesenchymal transition. In addition, DPSCs migrated towards tumour cells in vitro, which could not be confirmed after their in vivo intravenous, intraperitoneal or peritumoural injection under the tested experimental conditions. CONCLUSIONS: Our research suggests that intratumourally delivered DPSCs might be used as safe factories for the continuous delivery of anti-cancer drugs in HNC. Nevertheless, further optimization as well as efficacy studies are necessary to understand and improve in vivo tumour homing and determine the optimal experimental set-up of stem cell-based cancer therapies, including dosing and timing.sponsorship: G.M. was supported by 'Bijzonder Onderzoeksfonds' of Hasselt University (BOF, BOF16DOC06). M.L.M. was funded by 'Bijzonder Onderzoeksfonds' and 'Fonds Special de Recherche' (BOF16DOCNA02-FSR-confin UHasselt-UNamur). This research was further supported by research grants to I.L., U.H., A.B. and E.W. fromthe Research Foundation Flanders ('Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO)', grant numbers G0C1916FWO, 1517916 N and G0A7514N), BOF of Hasselt University (BOF20TT04), Limburg Cancer foundation ('Limburgs kankerfonds' LIKAF) and KU Leuven for PF 10/017 IMIR. The funding bodies played no role in study design, data collection, analysis and interpretation, or writing of the manuscript. ('Bijzonder Onderzoeksfonds' of Hasselt University (BOF)|BOF16DOC06, Bijzonder Onderzoeksfonds, Fonds Special de Recherche|BOF16DOCNA02-FSR-confin UHasselt-UNamur, Research Foundation Flanders ('Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO)'|G0C1916FWO, Research Foundation Flanders ('Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO)'|1517916 N, Research Foundation Flanders ('Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO)'|G0A7514N, BOF of Hasselt University|BOF20TT04, Limburg Cancer foundation ('Limburgs kankerfonds' LIKAF), KU Leuven|PF 10/017 IMIR)status: Publishe
Preconditioning of Human Dental Pulp Stem Cells with Leukocyte- and Platelet-Rich Fibrin-Derived Factors Does Not Enhance Their Neuroregenerative Effect
No full textPathologies of the central nervous system are characterized by loss of brain tissue and neuronal function which cannot be adequately restored by endogenous repair processes. This stresses the need for novel treatment options such as cell-based therapies that are able to restore damaged tissue or stimulate repair. This study investigated the neuroregenerative potential of the conditioned medium of human dental pulp stem cells (CM-hDPSCs) on neural stem cell (NSC) proliferation and migration as well as on neurite outgrowth of primary cortical neurons (pCNs). Additionally, the effect of leukocyte- and platelet-rich fibrin (L-PRF) priming on the neuroregenerative potential of the hDPSC secretome on NSCs and pCNs was evaluated. L-PRF contains factors that enhance stem cell-induced regeneration, but its effect on hDPSC-mediated neuroregeneration is unknown. This study demonstrated that CM-hDPSCs enhanced neuritogenesis. Moreover, CM-hDPSCs had a chemoattractant effect on NSCs. Although priming hDPSCs with L-PRF increased brain-derived neurotrophic factor secretion, no additional effects on the paracrine-mediated repair mechanisms were observed. These data support the neuroregenerative potential of hDPSCs, and although priming had no additional effect, the potential of L-PRF-primed hDPSCs on distinct regenerative mechanisms remains to be clarified
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Chorioallantoic membrane assay as model for angiogenesis in tissue engineering : focus on stem cells
Full text linkTissue engineering aims to structurally and functionally regenerate damaged tissues, which requires the formation of new blood vessels that supply oxygen and nutrients by the process of angiogenesis. Stem cells are a promising tool in regenerative medicine due to their combined differentiation and paracrine angiogenic capacities. The study of their proangiogenic properties and associated potential for tissue regeneration requires complex in vivo models comprising all steps of the angiogenic process. The highly vascularized extraembryonic chorioallantoic membrane (CAM) of fertilized chicken eggs offers a simple, easy accessible, and cheap angiogenic screening tool compared to other animal models. Although the CAM assay was initially primarily performed for evaluation of tumor growth and metastasis, stem cell studies using this model are increasing. In this review, a detailed summary of angiogenic observations of different mesenchymal, cardiac, and endothelial stem cell types and derivatives in the CAM model is presented. Moreover, we focus on the variation in experimental setup, including the benefits and limitations of in ovo and ex ovo protocols, diverse biological and synthetic scaffolds, imaging techniques, and outcome measures of neovascularization. Finally, advantages and disadvantages of the CAM assay as a model for angiogenesis in tissue engineering in comparison with alternative in vivo animal models are described
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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