Bridging the gap: Adipose tissue-based therapy for dermal scarring

Maroesjka Spiekman

Bridging the gap: Adipose tissue-based therapy for dermal scarring

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In dit proefschrift hebben we het gebruik van eigen vetweefsel als therapie voor littekens onderzocht. Vetweefsel kan door middel van liposuctie verkregen worden en ingespoten worden in en onder littekens van de huid. Dit wordt al lange tijd gebruikt in de plastische chirurgie als littekenbehandeling en lijkt verbetering van littekens te geven. Hiervoor ontbreekt echter nog sluitend wetenschappelijk bewijs.

In onze patiëntenstudie hebben we vet ingespoten in littekens die klachten (bijvoorbeeld pijn) geven. Lipofilling leidt bij deze patiënten tot een vermindering van klachten, waarbij de littekens meer gaan lijken op normale huid. Ook vinden er microscopische veranderingen in het littekenweefsel plaats, die wijzen op regeneratie.

Daarnaast hebben we in het laboratorium laten zien dat volwassen stromale (stam)cellen uit vetweefsel activatie van huidbindweefselcellen (huidfibroblasten) kan remmen: overmatige activatie van deze cellen zorgt voor littekenvorming. Groeifactoren van (stam)cellen uit vet zouden dus als therapie ter voorkoming van littekens kunnen dienen.

Echter, het verkrijgen van deze stromale (stam)cellen uit vet is een tijdrovend proces. Daarom hebben we in dit proefschrift verschillende manieren onderzocht om voldoende stromale (stam)cellen uit vet te verkrijgen voor gebruik in patiënten. Als eerste hebben we stromale (stam)cellen uit vet in het laboratorium sneller laten groeien met behulp van extra groeifactoren uit menselijke bloedplaatjes. Daarnaast hebben we verschillende manieren vergeleken om tijdens operaties snel stromale (stam)cellen uit vet te verkrijgen. Hiervan testen we op het moment nog één van deze methoden in een klinische placebo-gecontroleerde patiëntenstudie, om te zien of inspuiten van de stromale (stam)celfractie de vorming van ontsierende littekens kan tegengaan.

Concluderend, hebben we in dit proefschrift aangetoond dat lipofilling en stromale (stam)cellen uit vetweefsel kunnen bijdragen aan de behandeling van littekens.

Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Harmsen, Marco, Supervisor van der Lei, Berend, Supervisor Krenning, Guido, Co-supervisor Jonkman, Marcel F., Beoordelingscommissie Bank, Ruud, Beoordelingscommissie van Zuijlen, Paul P. M., Beoordelingscommissie, Externe Persoon
Datum van toekenning	20-jun.-2018
Plaats van publicatie	[Groningen]
Uitgever	Rijksuniversiteit Groningen
Gedrukte ISBN's	978-94-034-0664-0
Elektronische ISBN's	978-94-034-0663-3
Status	Published - 2018

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Title and contentsFinal publisher's version, 283 KB
Chapter 1Final publisher's version, 5,81 MB
Chapter 2Final publisher's version, 5,36 MB
Chapter 3Final publisher's version, 9,77 MB
Chapter 4Final publisher's version, 3,53 MB
Chapter 5Final publisher's version, 2,04 MB
Chapter 6Final publisher's version, 5,22 MB
Chapter 7Final publisher's version, 4,5 MB
Chapter 8Final publisher's version, 14,3 MB
Chapter 9Final publisher's version, 3,37 MB
Chapter 10Final publisher's version, 816 KB
AppendicesFinal publisher's version, 982 KB
Complete thesisFinal publisher's version, 46,7 MB
PropositionsFinal publisher's version, 136 KB

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@phdthesis{23ea1d0c6c7c4944a8819d624ca4d3ea,

title = "Bridging the gap: Adipose tissue-based therapy for dermal scarring",

abstract = "In this thesis, we have investigated the anti-scarring effects of adipose tissue using a multi-disciplinary approach. Lipofilling is a safe and simple autologous treatment for dermal scars. Review of the available scientific literature revealed that the general consensus is that lipofilling improves scar appearance and relieves scar-related pain. Still, placebo controlled trials to definitively confirm effectivity of lipofilling for dermal scarring have yet to conducted.In our own clinical trial, we demonstrated that lipofilling decreases severity of the scarring and normalized scar appearance towards normal skin. Moreover, analysis of scar tissues before and after lipofilling also demonstrated improvement of the scar tissues, pointing towards a regenerative effect.In the laboratory, we showed that adipose tissue derived stem/stromal cells (ASC) could inhibit activation of dermal fibroblasts. Excessive activation of dermal fibroblasts leads to scarring. We have shown that growth factors produced by ASC inhibit this process and could thus be used as therapy for scarring.However, obtaining large amounts of ASC that are needed for cell therapy in patients, remained a problem. In this thesis, we investigated different methods to obtain enough ASC for cell therapy. We showed that use of human platelet concentrates speeds up growth of ASC in the laboratory. Also, we compared different methods to isolate the stem/stromal cell fraction during surgery. Currently, we are testing one of these methods in a randomized, placebo-controlled patient study to investigate if injection of the stem/stromal cell fraction directly after surgery can prevent formation of pathological scars. The results of this study are still underway.In conclusion, we have shown in this thesis that lipofilling and the stem/stromal cell fraction of adipose tissue are a promising treatment for treatment and prevention of dermal scars.",

author = "Maroesjka Spiekman",

year = "2018",

language = "English",

isbn = "978-94-034-0664-0",

publisher = "Rijksuniversiteit Groningen",

school = "University of Groningen",

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TY - BOOK

T1 - Bridging the gap

T2 - Adipose tissue-based therapy for dermal scarring

AU - Spiekman, Maroesjka

PY - 2018

Y1 - 2018

N2 - In this thesis, we have investigated the anti-scarring effects of adipose tissue using a multi-disciplinary approach. Lipofilling is a safe and simple autologous treatment for dermal scars. Review of the available scientific literature revealed that the general consensus is that lipofilling improves scar appearance and relieves scar-related pain. Still, placebo controlled trials to definitively confirm effectivity of lipofilling for dermal scarring have yet to conducted.In our own clinical trial, we demonstrated that lipofilling decreases severity of the scarring and normalized scar appearance towards normal skin. Moreover, analysis of scar tissues before and after lipofilling also demonstrated improvement of the scar tissues, pointing towards a regenerative effect.In the laboratory, we showed that adipose tissue derived stem/stromal cells (ASC) could inhibit activation of dermal fibroblasts. Excessive activation of dermal fibroblasts leads to scarring. We have shown that growth factors produced by ASC inhibit this process and could thus be used as therapy for scarring.However, obtaining large amounts of ASC that are needed for cell therapy in patients, remained a problem. In this thesis, we investigated different methods to obtain enough ASC for cell therapy. We showed that use of human platelet concentrates speeds up growth of ASC in the laboratory. Also, we compared different methods to isolate the stem/stromal cell fraction during surgery. Currently, we are testing one of these methods in a randomized, placebo-controlled patient study to investigate if injection of the stem/stromal cell fraction directly after surgery can prevent formation of pathological scars. The results of this study are still underway.In conclusion, we have shown in this thesis that lipofilling and the stem/stromal cell fraction of adipose tissue are a promising treatment for treatment and prevention of dermal scars.

AB - In this thesis, we have investigated the anti-scarring effects of adipose tissue using a multi-disciplinary approach. Lipofilling is a safe and simple autologous treatment for dermal scars. Review of the available scientific literature revealed that the general consensus is that lipofilling improves scar appearance and relieves scar-related pain. Still, placebo controlled trials to definitively confirm effectivity of lipofilling for dermal scarring have yet to conducted.In our own clinical trial, we demonstrated that lipofilling decreases severity of the scarring and normalized scar appearance towards normal skin. Moreover, analysis of scar tissues before and after lipofilling also demonstrated improvement of the scar tissues, pointing towards a regenerative effect.In the laboratory, we showed that adipose tissue derived stem/stromal cells (ASC) could inhibit activation of dermal fibroblasts. Excessive activation of dermal fibroblasts leads to scarring. We have shown that growth factors produced by ASC inhibit this process and could thus be used as therapy for scarring.However, obtaining large amounts of ASC that are needed for cell therapy in patients, remained a problem. In this thesis, we investigated different methods to obtain enough ASC for cell therapy. We showed that use of human platelet concentrates speeds up growth of ASC in the laboratory. Also, we compared different methods to isolate the stem/stromal cell fraction during surgery. Currently, we are testing one of these methods in a randomized, placebo-controlled patient study to investigate if injection of the stem/stromal cell fraction directly after surgery can prevent formation of pathological scars. The results of this study are still underway.In conclusion, we have shown in this thesis that lipofilling and the stem/stromal cell fraction of adipose tissue are a promising treatment for treatment and prevention of dermal scars.

M3 - Thesis fully internal (DIV)

SN - 978-94-034-0664-0

PB - Rijksuniversiteit Groningen

CY - [Groningen]

ER -

Bridging the gap: Adipose tissue-based therapy for dermal scarring

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