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Stammzell-basierter biologischer Gefäßersatz

Stem cell-based strategies in vascular surgery

  • Leitthema
  • Published:
Gefässchirurgie Aims and scope Submit manuscript

Zusammenfassung

Eine chronisch-kritische Ischämie bei Patienten mit zugrunde liegender arterieller Verschlusskrankheit erfordert rekonstruktive vaskuläre chirurgische Eingriffe, die bislang mit körpereigenen Venensegmenten oder synthetischem Gefäßmaterial durchgeführt werden. Die begrenzte Verfügbarkeit von geeigneten autologen Gefäßtransplantaten mit niedrigem Durchmesser bei vielen Patienten und die offensichtlichen Nachteile von synthetischem Bypassmaterial zeigen die Notwendigkeit zur Entwicklung von klinisch verwendbaren biologisch konstruierten Blutgefäßsubstituten auf. Trotz erheblicher Fortschritte in diesem Bereich in den letzten zwei Jahrzehnten war ihre Implementierung in die klinische Routine eine Herausforderung. Die begrenzte replikative Lebensdauer von menschlichen adulten Gefäßzellen und ihre langsame Rate bei der Produktion von Kollagenmatrix in vitro stellten gravierende Probleme bei der Entwicklung mechanisch robuster und biologisch funktioneller künstlicher Transplantate dar. Mit den jüngsten Fortschritten in der Stammzellenforschung sind neue Zelltypen für das vaskuläre Tissue-Engineering verfügbar geworden. Insbesondere die Entdeckung von humanen induzierten pluripotenten Stammzellen (iPS-Zellen), die aus adulten differenzierten Zellen stammen, sowie von humanen multipotenten adulten mesenchymalen Stammzellen (ohne Genmodifizierungen und den mit ihnen verbundenen Sicherheitsbedenken) können die Entwicklung von neuem autologem Zellgewebe vorantreiben. Wir stellen die aktuellen Entwicklungen auf dem Gebiet der vaskulären Progenitorzellen vor und diskutieren die Möglichkeiten und Herausforderungen für den klinischen Einsatz von biologisch konstruierten Gefäßsubstituten.

Abstract

Critical chronic ischemia in patients with underlying arterial occlusive disease requires vascular reconstructive surgery. The limited supply of suitable small-diameter autologous vascular grafts in many patients and obvious disadvantages of synthetic bypass material demand the development of clinically usable tissue-engineered blood vessel substitutes. Despite substantial progress in the field over the last two decades, their implementation into the clinical routine has been challenging. The limited replicative life span of human adult vascular cells and their slow rate of collagenous matrix production in vitro have posed important problems in the development of mechanically robust and biologically functional engineered grafts. With recent advances in stem cell research, new cell sources for vascular tissue engineering have become available. In particular, the discovery of human induced pluripotent stem (iPS) cells derived from adult differentiated cells, as well as of human multipotent adult mesenchymal stem cells without gene modification requirements and related safety concerns, may advance the development of novel autologous cell-based tissue engineering approaches. Here we discuss recent developments in the field of vascular progenitor cells and opportunities and challenges for the clinical translation of stem cell-engineered vascular tissue substitutes.

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Förderung

Diese Arbeit wurde vom National Eye Institute, National Institutes of Health (NEI/NIH), mit Forschungsgeldern für M.H. Frank gefördert (RO1EY025794).

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Authors and Affiliations

  1. Chirurgische Klinik I, Universitätsklinikum Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Deutschland

    M. Gasser

  2. Transplant Research Program, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA

    M. H. Frank

  3. School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australien

    M. H. Frank

  4. Chirurgische Klinik I, Molekulare Onkologie und Immunologie, Universitätsklinikum Würzburg, Würzburg, Deutschland

    A. M. Waaga-Gasser

  5. Transplantation Research Center, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    A. M. Waaga-Gasser

Authors
  1. M. Gasser
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  2. M. H. Frank
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  3. A. M. Waaga-Gasser
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Correspondence to M. Gasser.

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Interessenkonflikt

M. Gasser, M. H. Frank und A. M. Waaga-Gasser geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Gasser, M., Frank, M.H. & Waaga-Gasser, A.M. Stammzell-basierter biologischer Gefäßersatz. Gefässchirurgie 23, 28–33 (2018). https://doi.org/10.1007/s00772-017-0349-5

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  • DOI: https://doi.org/10.1007/s00772-017-0349-5

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