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Stammzellderivate bei Hautschäden nach Strahlenexposition

Stem cell derived therapy for cutaneous radiation exposure

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Zusammenfassung

Strahlenbedingte Schädigungen der Haut führen zu einer Reihe deterministischer Effekte, so u. a. zu inflammatorischen Reaktionen und Zelldepletion. Daraus entstehen in einer bestimmten Reihenfolge distinkte klinische Symptome. Die Behandlungsansätze sind immer noch eingeschränkt, eine Restitutio ad integrum der betroffenen Bereiche ist bisher nicht möglich. In den vergangenen Jahren hat die experimentelle Forschung zur Generierung und Verabreichung autologer Stammzellen (SC) auch im Bereich der strahlenbedingten Läsionen weitere Fortschritte erzielt. Anhand der im Beitrag besprochenen Evidenz wird deutlich, dass die Stammzelltransplantationen nicht unbedingt nur durch den Ersatz geschädigter Zellen wirken, sondern höchstwahrscheinlich im Wesentlichen durch einen parakrinen Effekt. Die transplantierten Zellen sezernieren bioaktive Faktoren, welche die Stimulierung von Host-Stammzellen initiieren und so zur Regeneration geschädigter Gewebe beitragen. Transplantierte Stammzellen produzieren trophische Faktoren, die auch die systemische Heilung nach Strahlenschädigungen unterstützen. Ferner kann die Applikation von Stammzellsekretomen in Form von konditionierten Medien, die Mikrovesikel oder Exosome enthalten, ebenso wirksam sein wie die Gabe der Stammzellen selbst. Diese Hypothese wird unterstützt durch Studien, in denen sich zellfreie hMSC(humane mesenchymale SC)-Derivate als zur Wundheilung geeignet erwiesen haben, sodass eine Gabe intakter Zellen nicht erforderlich war. In einem Ischämiemodell (Maus, Hinterpfote) konnten die Effekte einer MSC-Injektion auf Reperfusion und Regeneration den parakrinen Mechanismen und der lokalen Freisetzung arteriogener Zytokine zugeschrieben werden. Aus der weiteren Evaluierung des parakrinen Potenzials autologer SC können sich weitere therapeutische Optionen ergeben, sowohl für akute Schädigungen als auch für die langfristigen, chronischen Folgen kutaner Strahlenschäden.

Abstract

Radiation injury to skin results in a variety of deterministic effects including inflammatory reactions and cell depletion leading to distinct clinical symptoms following a defined time pattern. Therapeutic approaches are still limited, a complete restitution of affected areas is so far impossible. In the last few years increasing experimental knowledge about acquisition and administration of autologous stem cells also in the field of radiation injuries has been obtained. Evidence reviewed in this article shows that the beneficial effects of stem cell transplantation are not necessarily due to the replacement of damaged cells by transplanted cells but most probably due in the most part to a paracrine effect. Transplanted cells secrete bioactive factors that initiate the stimulation of the host stem cells to regenerate the damaged tissues. Transplanted stem cells produce trophic factors which aid the systemic healing of the victims. Furthermore, administration of stem cell secretomes in the form of conditioned media containing microvesicles or exosomes can be as effective as administering the stem cells. This hypothesis is supported by findings that cell-free derivatives from hMSCs were useful for wound healing purposes and could circumvent the need for intact cells. Furthermore, the beneficial effect of MSC injection on reperfusion and tissue damage in a mouse model of hind limb ischemia could be attributed to paracrine mechanisms with local release of arteriogenic cytokines. Further evaluation of the paracrine potential of autologous stem cells may open new means for treatment of acute as well as chronic sequelae of cutaneous radiation injuries.

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Einhaltung ethischer Richtlinien

Interessenkonflikt. M. Rezvani gibt an, dass kein Interessenkonflikt besteht. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

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Authors and Affiliations

  1. Natural Biosciences SA, Lake Garden Medical Center, Kilchberg, Zurich, Switzerland

    M. Rezvani BSc, MSc, PhD, CBiol, FSB

  2. Faculty of Clinical Medicine, University of Oxford, Oxford, United Kingdom

    M. Rezvani BSc, MSc, PhD, CBiol, FSB

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  1. M. Rezvani BSc, MSc, PhD, CBiol, FSB
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Correspondence to M. Rezvani BSc, MSc, PhD, CBiol, FSB.

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Rezvani, M. Stammzellderivate bei Hautschäden nach Strahlenexposition. Hautarzt 64, 910–916 (2013). https://doi.org/10.1007/s00105-013-2629-7

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