Bedeutung mesenchymaler Stammzellen in der Viszeralmedizin

S. Gamba; Y. Zhao; L. Zhao; Y. Wang; B. Schwarz; S. Primo; K.-W. Jauch; P. J. Nelson; D. P. Modest; H. Nieß; C. Bruns

doi:10.1055/s-0032-1328561

Zentralblatt für Chirurgie - Zeitschrift für Allgemeine, Viszeral-, Thorax- und Gefäßchirurgie, Table of Contents

Zentralbl Chir 2015; 140(03): 294-303
DOI: 10.1055/s-0032-1328561

Übersicht

Georg Thieme Verlag KG Stuttgart · New York

Bedeutung mesenchymaler Stammzellen in der Viszeralmedizin

Significance of Mesenchymal Stem Cells in Gastrointestinal Disorders

S. Gamba

¹Chirurgische Klinik und Poliklinik, Campus Großhadern, Klinikum der Universität München, Deutschland

,

Y. Zhao

¹Chirurgische Klinik und Poliklinik, Campus Großhadern, Klinikum der Universität München, Deutschland

,

L. Zhao

¹Chirurgische Klinik und Poliklinik, Campus Großhadern, Klinikum der Universität München, Deutschland

,

Y. Wang

¹Chirurgische Klinik und Poliklinik, Campus Großhadern, Klinikum der Universität München, Deutschland

,

B. Schwarz

¹Chirurgische Klinik und Poliklinik, Campus Großhadern, Klinikum der Universität München, Deutschland

,

S. Primo

¹Chirurgische Klinik und Poliklinik, Campus Großhadern, Klinikum der Universität München, Deutschland

,

K.-W. Jauch

¹Chirurgische Klinik und Poliklinik, Campus Großhadern, Klinikum der Universität München, Deutschland

,

P. J. Nelson

²Medizinische Klinik und Poliklinik IV, Nephrologisches Zentrum und Arbeitsgruppe Klinische Biochemie, Campus Innenstadt, Klinikum der Universität München, Deutschland

,

D. P. Modest

³Medizinische Klinik und Poliklinik III, Campus Großhadern, Klinikum der Universität München, Deutschland

,

H. Nieß

¹Chirurgische Klinik und Poliklinik, Campus Großhadern, Klinikum der Universität München, Deutschland

,

C. Bruns

¹Chirurgische Klinik und Poliklinik, Campus Großhadern, Klinikum der Universität München, Deutschland

› Author Affiliations

Abstract

Zusammenfassung

In dieser Übersichtsarbeit wird der aktuelle Stand der experimentellen und klinischen Anwendung mesenchymaler Stammzellen (MSCs) in der Viszeralmedizin dargestellt. Neben dem Einsatz im regenerativen und immunologischen Kontext weckt diese Zellpopulation ebenso große Erwartungen im Bereich der Tumortherapie. Während in klinischen Studien zu chronisch-entzündlichen Darmerkrankungen und degenerativen Leberschäden bereits ein günstiger Effekt mesenchymaler Stammzellen demonstriert werden konnte, bildet die recht gegensätzliche Studienlage zu gastrointestinalen Tumoren das Potenzial anti-neoplastischer Therapieansätze durch MSCs noch nicht zufriedenstellend ab. Mesenchymale Stammzellen verfügen über ein breites Differenzierungspotenzial und sind in der Lage, über para- und endokrine Mechanismen den Vorgang der Wundheilung zu beeinflussen und immunologische Prozesse zu regulieren. Weiterhin bieten sie nach Transfektion die Möglichkeit einer zellbasierten Gentherapie. Zusammen mit der Fähigkeit zur tumorgerichteten Migration ergibt sich damit die Option einer gezielten Behandlung solider Tumoren mittels lokal exprimierter Substanzen, die zur Apoptose von Tumorzellen führen kann. In Hinblick auf die Vielfalt therapeutischer Optionen wird in dieser Übersichtsarbeit die Distribution exogen zugeführter MSCs im Organismus erläutert, die Möglichkeit einer Visualisierung der Verteilungsdynamik diskutiert und die Bedeutung unterschiedlicher Applikationsformen geklärt. Abschließend werden die Risiken mesenchymaler Stammzellen und damit die derzeitige Zurückhaltung der breiten klinischen Anwendung dargelegt.

Abstract

In this review we summarise the recent developments regarding the experimental and clinical use of mesenchymal stem cells (MSCs), focusing mainly on the treatment of gastrointestinal disorders. Next to their relevance in the field of regenerative medicine and immunology, this population of cells has also raised great expectations for possible applications in cancer therapy. While clinical trials were able to demonstrate the efficacy of MSCs in cases of inflammatory bowel disease and degenerative conditions of the liver, controversial results have been presented regarding their antineoplastic potential in gastrointestinal tumours. MSCs can differentiate into a large variety of specialised cells. They are capable of regulating both wound healing and immune responses through paracrine and endocrine signalling. Moreover, MSCs can be transfected with a great number of different therapeutic genes – considering their ability to selectively migrate towards neoplastic tissues, this feature allows for targeted therapy of solid tumours. Transfected genes can be designed so that they are expressed exclusively in the vicinity of the tumour, eventually triggering apoptosis in cancer cells. In this review, we demonstrate the natural distribution of exogenously applied MSCs in the host. Furthermore, we mention various methods of tracking MSCs in vivo and different parameters of administration that tend to influence therapeutic outcome (e.g., origin of MSCs, mode of application, or the potency of transfected genes). Finally, this review points out the hazards of MSC therapy, emphasising the risks related to their widespread clinical use.

Schlüsselwörter

mesenchymale Stammzellen - Viszeralmedizin - Krebs - Suizidgentherapie - zielgerichtete Krebstherapie

Key words

mesenchymal stem cells - gastrointestinal disorders - cancer - suicide gene therapy - targeted therapy

Full Text

References

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